调经助孕方对DOR模型大鼠卵泡发育障碍影响的实验研究
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摘要
目的：
通过灌胃雷公藤多苷片建立大鼠卵巢功能低下模型，观察中药复方“调经助孕方”对卵巢功能低下模型大鼠生殖系统的影响，初步探讨调经助孕方对改善卵巢储备功能、提高卵泡质量及内膜容受性的机理；并验证本方治疗因卵巢储备功能下降，卵泡发育障碍所致不孕症的有效性，为后期调经助孕方的中药新药研究开发提供一定的科学依据。
方法：
除空白对照组(简称空白组)大鼠以生理盐水10000mg/(kg·d)灌胃外，其余大鼠采用雷公藤多苷片50mg/(kg·d)连续2周灌胃以复制肾虚型卵巢储备功能下降致卵泡发育障碍的生殖功能低下动物模型，并至灌胃第8天起行阴道脱落细胞学涂片观察动情周期变化情况以确定造模情况。将造模成功的大鼠随机分为模型对照组(简称模型组)、中西药联合组(简称联合组)、西药组及调经助孕方组(简称中药组)。后其中空白组和模型组大鼠以10000mg/(kg·d)生理盐水灌胃；西药组大鼠予以激素替代加促排卵治疗。具体方法为先在第一个性周期5天内行激素替代治疗，连续5日予以戊酸雌二醇片0.12mg/(kg·d)，至第4天起加用黄体酮胶囊18mg/(kg·d)，后在下一性周期内于大鼠动情前期连续2天灌胃枸橼酸氯米芬片4.5mg/(kg·d)以行促排卵治疗；中药组按成人等效剂量灌胃调经助孕中药复方颗粒5250mg/(kg·d)，连续10天；中西药联合组则参照中药组及西药组给药方法和计量，给予中西药联合用药10天。
治疗后采用酶联免疫吸附法和化学发光免疫法分别检测血清促卵泡生成素、促黄体生成素、雌二醇、孕酮及抗苗勒氏管激素水平；利用组织病理学方法研究各组大鼠卵巢、子宫的形态及组织病理学改变，并统计各级卵泡及黄体计数；借助蛋白质印迹法观察卵巢内相关细胞因子：干细胞因子、生长分化因子-9及骨形态发生蛋白-15的蛋白表达水平变化；通过免疫组化法及末端脱氧核苷酸转移酶介导的dUTP缺口末端标记测定法分别观察卵巢细胞促凋亡基因Bax的表达情况及卵巢细胞凋亡率的变化；最后则运用实时荧光定量聚合酶链式反应法检测围着床期子宫内膜降钙素基因的表达情况以观察其容受性的变化。
结果：
1.对血清生殖激素的影响：模型组大鼠血清FSH、LH高于空白组，E2及AMH则较空白组低，均有统计学意义(P<0.01)。治疗后西药组和中药组大鼠血清各项生殖激素已恢复到正常水平，FSH、LH水平较模型组相比下降，E2及AMH水平则较模型组升高，差异均有统计学意义(P<0.01)，与空白组相比已不存在显著性差异(P>0.05)。
2.对脏器指数的影响：造模后模型组大鼠卵巢及子宫指数均低于空白组，二者间的差异有统计学意义(P<0.05)。治疗后，西药组和中药组的卵巢、子宫指数上升，与空白组不存在明显差异(P>0.05)，而与模型组相比，则有显著性差异(P<0.05)。
3.对卵巢、子宫显微结构的影响：HE切片光镜下可见空白组卵巢皮层中分布有许多原始卵泡，各级卵泡发育正常、卵泡形态大小各异，卵泡内卵母细胞大而圆，轮廓清晰，并见大量黄体；模型组卵巢中各级卵泡少见，卵泡直径小、卵泡内颗粒细胞层数较其余各组明显减少，有大量闭锁卵泡和白体，极少见黄体，髓质致密，血管较少；西药组和中药组卵巢内初级卵泡和次级卵泡发育较正常，可见卵泡内母细胞大而圆，轮廓清晰，可见黄体和闭锁细胞，髓质血管较丰富。
另空白组和中药组子宫内膜上皮细胞排列整齐，腺体和基质丰富；模型组子宫内膜上皮细胞排列紊乱，腺体减少，基质稀疏水肿，大量嗜酸性粒细胞浸润；西药组子宫内膜上皮细胞排列尚整齐，腺体和基质较丰富，少量嗜酸性粒细胞浸润。
4.对卵泡及黄体计数的影响：模型组大鼠卵巢内生长及成熟卵减少、黄体少见，闭锁卵泡增多，与空白组相比有极显著性差异(P<0.01)。经治疗后，西药组、中药组大鼠生长、成熟卵泡及黄体数均有明显增加，而闭锁卵泡减少，较模型组有很大改善(P<0.01)，与空白组间已无统计学差异(P>0.05)。其中，西药组生长卵泡数较空白组及中药组均明显增多(P<0.05)，而成熟卵泡、闭锁卵泡和黄体则与中药组无明显差异(P>0.05)。
5.对卵巢内细胞因子的影响：模型组卵巢内细胞因子SCF、GDF-9及BMP-15的蛋白定量表达水平均较空白组有明显下降，有显著性差异(P<0.05)。而经治疗后均能明显上调大鼠卵巢内这三种细胞因子的表达，西药、中药组的细胞因子蛋白表达量同空白组相比，差异不存在统计学意义(P>0.05)。
6.对卵巢细胞促凋亡基因Bax表达的影响：空白组大鼠卵巢细胞Bax基因阳性表达率较其余各组来说均处于明显低水平，其中与模型组及西药组间差异存在极显著性(P<0.01)；与中药组间则有显著差异(P<0.05)。经治疗后，西药组、中药组Bax基因阳性表达率较模型组有大幅下降，其二者同模型组间的差异均有统计学意义(P<0.01)，而其组间的差异则不没有统计学意义(P>0.05)。
7.对卵巢细胞凋亡率的影响：空白组大鼠的卵巢细胞凋亡率在所有组别中为最低水平，与余各组间的差异均存在极显著性(P<0.01)。西药、中药组经治疗后，虽凋亡率较模型组有大幅下降(P<0.01)，组间没有显著性差异(P>0.05)，但仍与空白组存在极显著性差异(P<0.01)。
8.对围着床期血清孕酮含量的影响：围着床期大鼠血清孕酮含量各组之间无显著性差异，空白组与西药组、中药组三组各组之间的差异均无统计学意义(P>0.05)。
9.对围着床期子宫内膜CT mRNA表达的影响：西药组大鼠围着床期时内膜CT mRNA表达水平较空白组、联合组与中药组来说均处于低水平，其间的差异均存在极显著的统计学意义(P<0.01)，虽中药组的表达水平稍高于空白组及联合组，但其三者间的差异均没有显著性(P>0.05)。
结论：
徐升阳教授认为卵巢功能低下，卵泡发育障碍所致不孕症患者中医辨证主要属肾虚，其中合并黄体功能不全者或兼夹肝郁之证，并以此提出了“补肾以促卵泡发育，调肝以利黄体功能，健脾以益内膜容受性”的观点，自拟“调经助孕方”以补肾益精、调经种子之法来治疗因卵巢储备功能下降，卵泡发育障碍所致不孕症或作为IVF-ET的辅助治疗。本实验研究表明，调经助孕方能通过下丘脑-垂体-卵巢生殖轴以调节紊乱的生殖激素水平、修复模型大鼠子宫、卵巢组织损伤并改善其显微结构的病理改变；同时可促进模型大鼠卵泡及黄体发育，减少闭锁卵泡的生成，并提高卵巢内相关细胞因子的蛋白表达量来调节模型大鼠卵巢的自/旁(邻)分泌功能；还能抑制模型大鼠卵巢内卵泡颗粒细胞的凋亡、减缓卵泡闭锁以正向调节卵泡的正常发育；除此之外，调经助孕方还能上调围着床期时子宫内膜CTmRNA的表达来提高内膜的容受性以利于胚胎的着床。
Objectives:
Gastric administration of Tripterygium Glycoside (TG) Pill was given tothe rats to establish ovarian dysfunction model through which to observe theeffects TiaoJingZhuYun decoction on reproductive system of rat with ovariandysfunction and study futher the mechanism of this decoction in strengtheningovarian reserve, improving follicle qualilty and enhancing the endometriumreceptivity.Furth more, verified clinical curative effect on infertility caused byDecreasing Ovarian Reserve (DOR) and follicle development dysfunction canprovide a scientific evidence to some degree for the research in developingpatterned Chinese herbal products.
Methods：
The placebo group (P group) were perfused with physiological saline bydoes in10000mg/(kg·d), TG were administered to the rest for2consecutiveweeks to copy the model of low reproduction for follicle developmentdysfunction caused by DOR deemed as insufficiency of kidney. In the meantime, conduct viginal exfoliate cells test to observe the change in estrus so asto ensure whether the model was induced successfully.
Next, the model-induced rats were randomized into model control group(M group), weartern medicine treated group (W group), Chinese herb treatedgroup (H group), combination group (C group). Then, P group and M groupwere perfused with physiological saline by does in10000mg/(kg·d). Whereas,conduct hormone replacement therapy (HRT) and ovarian stimulation in Wgroup. It comes specificly as below: implement HRT in1stestrus, perfuse ratswith Estradiol Valerate Tablete by does in0.12mg/(kg·d) for5sucessive daysbut add Progesterone Capsule by does in18mg/(kg·d) on4thday, thenadminister Clomifene Citrate Tablet to rats by does4.5mg/(kg·d) to conductovarian stimulation therapy for2consecutive days before the next proestrus.H group were ferfused with TiaoJingZhuYun complex priscription powder bydoes in5250mg/(kg·d) for10sucessive days. C group were treated withcombination of Chinese herb&Werstern drugs, and the does was the same asthe former2groups respectively.
Adopting Enzyme Linked Immunosorbent Assay (ELISA) andChemiluminescence Immuno Assay (CLIA) after the therapy to detect thelevel of Follicle Stimulating Hormone(FSH)、 Luteinizing Hormone (LH)、Estradiol (E2)、 Progesterone (P) and Anti-Müellerian hormone (AMH)respectively. Taking advantage of Pathology to study the shape andPathological change of rats’ ovaries ang uteries, and make a statistics of thecount of follicles on each rank and corpus luteum. Observing the change onthe level of protein expressed of ovarian relevant cytokines by means ofWestern Blot. Watching the expression condition of ovarian cellspro-apoptotic gene Bax and the change on apoptosis rate throughImmunohistochemical Method and TdT-mediated Dutp Nick-End Labeling(TUNEL). Detecting the expression of endometrium Calcitonin inperi-implantation by Real-Time Quantitative Polymerase Chain Reaction(RT-PCR) to inspect the change of its receptivity comes to the final step.
Results:
1. Impact on the reproductive hormone in serum: FSH and LH of Mgroup were higher than that of P group; whereas, E2and AMH were lowercompared with P group, which maked a statistical significance (P<0.01). Thehormone level of W group and H group has recovered to the normalrespectively after the therapy, FSH and LH decended but E2and AMH rised incomparision with M group, which counted a lot in statistic, on the contrast, thedifference with P group didn’t make any sense.
2. Influence on the organ index: There was statistical significancebetween the P group and M group refer to the ovary and womb index whichwere lower in M group than in P group. But index in W group and H grouphas got up, not making a statistical significance (P>0.05) when compared withP group after the therapy.In contrast to M group, it did not (P<0.05).
3. Effect on the microstructure of ovary and womb: a scale of primitivefollicle can be spotted in HE section by light microscope in ovarian cortex of Pgroup. The size and shape of follicle on every stage which developed normallyvaried. Oocytes were both large and round that were in distinct outline, andcorpus luteum in large amount can be caught.Follicles on each stage whichhad a short diameter were barely spotted in M group. Layers of granulosa cellsin follicle had reduced in comparision with other groups. There were also alarge sun of atrefic follicles and corpus albicans and infrequent corpus luteum.The medella of ovary were intensive and its blood vessels were fewer. Firstand second rank follicles in W group and H group developed in the normalway and the condition oocytes were the same as P group but atrefic folliclescan be seen and abundance in the blood vessels of medulla.
Endometrial epithelial cells of P group and H group arranged orderly,glands and matrix were abundant.Whereas, the cells of M group were indisorder with decreasing glands and sparse papilledema matrix as well as massive infiltrating ensinophilic granulocyte. But the situation in W groupwere opposite.
4. Impact on the count of follicle and corpus luteum: The developing andmature follicles has reduced with infrequent corpus luteum and increasingatrefic follicles in M group which maked a great statistical significance(P<0.01) compared with P group. After therapy, the developing and maturefollicles has increased obviously and atrefic follicles has reduced, improving alot in comparision with M group (P<0.01) and making any sense opposed to Pgroup (P>0.05). What was emphasize was that the developing follicles in Wgroup were up apparent than that in P group and H group (P<0.01), but thedistinction of mature follicles and atrefic follicles as well as corpus luteum canbe neglected (P>0.05).
5. Influence on cytokines in ovary: The level of quantitative protein beingencoded of cytokines such as Stem Cell Growth Factor (SCF)、HumanGrowth Differentiation Factor-9(GDF-9) and Bone Morphogenetic Protein-15(BMP-15) has clearly decended opposed to P group, making a statisticalsignificance (P<0.05). Even though the expressin of three cytokines in Wgroup and H group has been evidential up-regulated, the distinct with P groupmake any sense (P>0.05).
6. Effect on the expression of ovarian cell pro-apoptotic gene Bax: Thepositive expression ratio of ovarian cell pro-apoptotic gene Bax in P groupwere manifest lower than the rest, making a statistical significance with Mgroup and W group (P<0.01) but a bit difference compared with H group(P<0.05). The positive expression rate of pro-apoptotic gene Bax in W groupand H group were much lower than that in M group after the therapy. Thoughthe divergence between M group has statistical significance (P<0.01), thedifference between W group and H group can be ignored (P>0.05).
7. Impact on the apoptosis rate of ovarian cell: The apoptosis rate ofovarian cell in P group was at the bottom among all the groups and thedivergence was much evidential compared to the other groups respectively(P<0.01). When the W group ang H group got treated even though theapoptosis rate has descended a lot in comparision with M group (P<0.01) anddifference made no sence between the two groups (P>0.05), there was stillstatistical significance (P<0.01) opposed to P group.
8. Influence on the content of serum Progesterone in peri-implantation:There was no manifest differense among groups. Divergence between Pgroup、H group and W group can be neglected (P>0.05).
9. Effected on the expression of endometrium CT mRNA inperi-implantation: The expression level of endometrium CT mRNA of Wgroup in peri-implantation was the lowest in comparision with P group、Cgroup and H group,making a great statistical significance (P<0.01). Specificly,the expression level of H group was a bit higer than that of P group and Cgroup, but the difference between the three groups maked no sense (P>0.05).
Conclusions:
Professor Shengyang Xu clings to the perspective that it is primary insufficiency of kidney Essence and Qi and partly hepatic stagnation whenmerged with luteal insufficiency based on syndrome differentiation thatcontributes to infertility as the result of DOR and follicle developmentdysfunction. So, he puts forwards the decoction of regulate menstruation forpregnancy promotion, a creative achievement from his perspective which isfocused on nourishing kidney to foster the development of follicle, smoothingliver to improve the function of corpus luteum, and enhancing theendometrium receptivity by strengthening the spleen as the therapy of this disease or supplementary for In Vitro Fertilization And Embryo Transfer(IVF-ET).
This experimental research show that TiaoJingZhuYun decoction canregulate the disordered hormorne level, renovate model rats injured womb andovarian tissue as well as mitigate pathological change of microstructure bymeans of Hypothalamus-Pituitary-Ovary Axis. What’s more, it’s able to fosterthe development of follicle and corpus leteum, reduce the amount of atreficfollicle, accumulate the protein that relevant cytokines in ovarian encodes toregulate the function of model rats autocrine and paracrine as well asjustacrine, depress apoptosis of rats granulosa cells, slacken atrefic follicle toadjust it to cultivate in forward direction. Finally, TiaoJingZhuYun decoctioncan upgrade the expression of endometrium CT mRNA in peri-implantationfor enhancing the endometrium receptivity which can lay the foundation ofembryo implantation.
通过灌胃雷公藤多苷片建立大鼠卵巢功能低下模型，观察中药复方“调经助孕方”对卵巢功能低下模型大鼠生殖系统的影响，初步探讨调经助孕方对改善卵巢储备功能、提高卵泡质量及内膜容受性的机理；并验证本方治疗因卵巢储备功能下降，卵泡发育障碍所致不孕症的有效性，为后期调经助孕方的中药新药研究开发提供一定的科学依据。
方法：
除空白对照组(简称空白组)大鼠以生理盐水10000mg/(kg·d)灌胃外，其余大鼠采用雷公藤多苷片50mg/(kg·d)连续2周灌胃以复制肾虚型卵巢储备功能下降致卵泡发育障碍的生殖功能低下动物模型，并至灌胃第8天起行阴道脱落细胞学涂片观察动情周期变化情况以确定造模情况。将造模成功的大鼠随机分为模型对照组(简称模型组)、中西药联合组(简称联合组)、西药组及调经助孕方组(简称中药组)。后其中空白组和模型组大鼠以10000mg/(kg·d)生理盐水灌胃；西药组大鼠予以激素替代加促排卵治疗。具体方法为先在第一个性周期5天内行激素替代治疗，连续5日予以戊酸雌二醇片0.12mg/(kg·d)，至第4天起加用黄体酮胶囊18mg/(kg·d)，后在下一性周期内于大鼠动情前期连续2天灌胃枸橼酸氯米芬片4.5mg/(kg·d)以行促排卵治疗；中药组按成人等效剂量灌胃调经助孕中药复方颗粒5250mg/(kg·d)，连续10天；中西药联合组则参照中药组及西药组给药方法和计量，给予中西药联合用药10天。
治疗后采用酶联免疫吸附法和化学发光免疫法分别检测血清促卵泡生成素、促黄体生成素、雌二醇、孕酮及抗苗勒氏管激素水平；利用组织病理学方法研究各组大鼠卵巢、子宫的形态及组织病理学改变，并统计各级卵泡及黄体计数；借助蛋白质印迹法观察卵巢内相关细胞因子：干细胞因子、生长分化因子-9及骨形态发生蛋白-15的蛋白表达水平变化；通过免疫组化法及末端脱氧核苷酸转移酶介导的dUTP缺口末端标记测定法分别观察卵巢细胞促凋亡基因Bax的表达情况及卵巢细胞凋亡率的变化；最后则运用实时荧光定量聚合酶链式反应法检测围着床期子宫内膜降钙素基因的表达情况以观察其容受性的变化。
结果：
1.对血清生殖激素的影响：模型组大鼠血清FSH、LH高于空白组，E2及AMH则较空白组低，均有统计学意义(P<0.01)。治疗后西药组和中药组大鼠血清各项生殖激素已恢复到正常水平，FSH、LH水平较模型组相比下降，E2及AMH水平则较模型组升高，差异均有统计学意义(P<0.01)，与空白组相比已不存在显著性差异(P>0.05)。
2.对脏器指数的影响：造模后模型组大鼠卵巢及子宫指数均低于空白组，二者间的差异有统计学意义(P<0.05)。治疗后，西药组和中药组的卵巢、子宫指数上升，与空白组不存在明显差异(P>0.05)，而与模型组相比，则有显著性差异(P<0.05)。
3.对卵巢、子宫显微结构的影响：HE切片光镜下可见空白组卵巢皮层中分布有许多原始卵泡，各级卵泡发育正常、卵泡形态大小各异，卵泡内卵母细胞大而圆，轮廓清晰，并见大量黄体；模型组卵巢中各级卵泡少见，卵泡直径小、卵泡内颗粒细胞层数较其余各组明显减少，有大量闭锁卵泡和白体，极少见黄体，髓质致密，血管较少；西药组和中药组卵巢内初级卵泡和次级卵泡发育较正常，可见卵泡内母细胞大而圆，轮廓清晰，可见黄体和闭锁细胞，髓质血管较丰富。
另空白组和中药组子宫内膜上皮细胞排列整齐，腺体和基质丰富；模型组子宫内膜上皮细胞排列紊乱，腺体减少，基质稀疏水肿，大量嗜酸性粒细胞浸润；西药组子宫内膜上皮细胞排列尚整齐，腺体和基质较丰富，少量嗜酸性粒细胞浸润。
4.对卵泡及黄体计数的影响：模型组大鼠卵巢内生长及成熟卵减少、黄体少见，闭锁卵泡增多，与空白组相比有极显著性差异(P<0.01)。经治疗后，西药组、中药组大鼠生长、成熟卵泡及黄体数均有明显增加，而闭锁卵泡减少，较模型组有很大改善(P<0.01)，与空白组间已无统计学差异(P>0.05)。其中，西药组生长卵泡数较空白组及中药组均明显增多(P<0.05)，而成熟卵泡、闭锁卵泡和黄体则与中药组无明显差异(P>0.05)。
5.对卵巢内细胞因子的影响：模型组卵巢内细胞因子SCF、GDF-9及BMP-15的蛋白定量表达水平均较空白组有明显下降，有显著性差异(P<0.05)。而经治疗后均能明显上调大鼠卵巢内这三种细胞因子的表达，西药、中药组的细胞因子蛋白表达量同空白组相比，差异不存在统计学意义(P>0.05)。
6.对卵巢细胞促凋亡基因Bax表达的影响：空白组大鼠卵巢细胞Bax基因阳性表达率较其余各组来说均处于明显低水平，其中与模型组及西药组间差异存在极显著性(P<0.01)；与中药组间则有显著差异(P<0.05)。经治疗后，西药组、中药组Bax基因阳性表达率较模型组有大幅下降，其二者同模型组间的差异均有统计学意义(P<0.01)，而其组间的差异则不没有统计学意义(P>0.05)。
7.对卵巢细胞凋亡率的影响：空白组大鼠的卵巢细胞凋亡率在所有组别中为最低水平，与余各组间的差异均存在极显著性(P<0.01)。西药、中药组经治疗后，虽凋亡率较模型组有大幅下降(P<0.01)，组间没有显著性差异(P>0.05)，但仍与空白组存在极显著性差异(P<0.01)。
8.对围着床期血清孕酮含量的影响：围着床期大鼠血清孕酮含量各组之间无显著性差异，空白组与西药组、中药组三组各组之间的差异均无统计学意义(P>0.05)。
9.对围着床期子宫内膜CT mRNA表达的影响：西药组大鼠围着床期时内膜CT mRNA表达水平较空白组、联合组与中药组来说均处于低水平，其间的差异均存在极显著的统计学意义(P<0.01)，虽中药组的表达水平稍高于空白组及联合组，但其三者间的差异均没有显著性(P>0.05)。
结论：
徐升阳教授认为卵巢功能低下，卵泡发育障碍所致不孕症患者中医辨证主要属肾虚，其中合并黄体功能不全者或兼夹肝郁之证，并以此提出了“补肾以促卵泡发育，调肝以利黄体功能，健脾以益内膜容受性”的观点，自拟“调经助孕方”以补肾益精、调经种子之法来治疗因卵巢储备功能下降，卵泡发育障碍所致不孕症或作为IVF-ET的辅助治疗。本实验研究表明，调经助孕方能通过下丘脑-垂体-卵巢生殖轴以调节紊乱的生殖激素水平、修复模型大鼠子宫、卵巢组织损伤并改善其显微结构的病理改变；同时可促进模型大鼠卵泡及黄体发育，减少闭锁卵泡的生成，并提高卵巢内相关细胞因子的蛋白表达量来调节模型大鼠卵巢的自/旁(邻)分泌功能；还能抑制模型大鼠卵巢内卵泡颗粒细胞的凋亡、减缓卵泡闭锁以正向调节卵泡的正常发育；除此之外，调经助孕方还能上调围着床期时子宫内膜CTmRNA的表达来提高内膜的容受性以利于胚胎的着床。
Objectives:
Gastric administration of Tripterygium Glycoside (TG) Pill was given tothe rats to establish ovarian dysfunction model through which to observe theeffects TiaoJingZhuYun decoction on reproductive system of rat with ovariandysfunction and study futher the mechanism of this decoction in strengtheningovarian reserve, improving follicle qualilty and enhancing the endometriumreceptivity.Furth more, verified clinical curative effect on infertility caused byDecreasing Ovarian Reserve (DOR) and follicle development dysfunction canprovide a scientific evidence to some degree for the research in developingpatterned Chinese herbal products.
Methods：
The placebo group (P group) were perfused with physiological saline bydoes in10000mg/(kg·d), TG were administered to the rest for2consecutiveweeks to copy the model of low reproduction for follicle developmentdysfunction caused by DOR deemed as insufficiency of kidney. In the meantime, conduct viginal exfoliate cells test to observe the change in estrus so asto ensure whether the model was induced successfully.
Next, the model-induced rats were randomized into model control group(M group), weartern medicine treated group (W group), Chinese herb treatedgroup (H group), combination group (C group). Then, P group and M groupwere perfused with physiological saline by does in10000mg/(kg·d). Whereas,conduct hormone replacement therapy (HRT) and ovarian stimulation in Wgroup. It comes specificly as below: implement HRT in1stestrus, perfuse ratswith Estradiol Valerate Tablete by does in0.12mg/(kg·d) for5sucessive daysbut add Progesterone Capsule by does in18mg/(kg·d) on4thday, thenadminister Clomifene Citrate Tablet to rats by does4.5mg/(kg·d) to conductovarian stimulation therapy for2consecutive days before the next proestrus.H group were ferfused with TiaoJingZhuYun complex priscription powder bydoes in5250mg/(kg·d) for10sucessive days. C group were treated withcombination of Chinese herb&Werstern drugs, and the does was the same asthe former2groups respectively.
Adopting Enzyme Linked Immunosorbent Assay (ELISA) andChemiluminescence Immuno Assay (CLIA) after the therapy to detect thelevel of Follicle Stimulating Hormone(FSH)、 Luteinizing Hormone (LH)、Estradiol (E2)、 Progesterone (P) and Anti-Müellerian hormone (AMH)respectively. Taking advantage of Pathology to study the shape andPathological change of rats’ ovaries ang uteries, and make a statistics of thecount of follicles on each rank and corpus luteum. Observing the change onthe level of protein expressed of ovarian relevant cytokines by means ofWestern Blot. Watching the expression condition of ovarian cellspro-apoptotic gene Bax and the change on apoptosis rate throughImmunohistochemical Method and TdT-mediated Dutp Nick-End Labeling(TUNEL). Detecting the expression of endometrium Calcitonin inperi-implantation by Real-Time Quantitative Polymerase Chain Reaction(RT-PCR) to inspect the change of its receptivity comes to the final step.
Results:
1. Impact on the reproductive hormone in serum: FSH and LH of Mgroup were higher than that of P group; whereas, E2and AMH were lowercompared with P group, which maked a statistical significance (P<0.01). Thehormone level of W group and H group has recovered to the normalrespectively after the therapy, FSH and LH decended but E2and AMH rised incomparision with M group, which counted a lot in statistic, on the contrast, thedifference with P group didn’t make any sense.
2. Influence on the organ index: There was statistical significancebetween the P group and M group refer to the ovary and womb index whichwere lower in M group than in P group. But index in W group and H grouphas got up, not making a statistical significance (P>0.05) when compared withP group after the therapy.In contrast to M group, it did not (P<0.05).
3. Effect on the microstructure of ovary and womb: a scale of primitivefollicle can be spotted in HE section by light microscope in ovarian cortex of Pgroup. The size and shape of follicle on every stage which developed normallyvaried. Oocytes were both large and round that were in distinct outline, andcorpus luteum in large amount can be caught.Follicles on each stage whichhad a short diameter were barely spotted in M group. Layers of granulosa cellsin follicle had reduced in comparision with other groups. There were also alarge sun of atrefic follicles and corpus albicans and infrequent corpus luteum.The medella of ovary were intensive and its blood vessels were fewer. Firstand second rank follicles in W group and H group developed in the normalway and the condition oocytes were the same as P group but atrefic folliclescan be seen and abundance in the blood vessels of medulla.
Endometrial epithelial cells of P group and H group arranged orderly,glands and matrix were abundant.Whereas, the cells of M group were indisorder with decreasing glands and sparse papilledema matrix as well as massive infiltrating ensinophilic granulocyte. But the situation in W groupwere opposite.
4. Impact on the count of follicle and corpus luteum: The developing andmature follicles has reduced with infrequent corpus luteum and increasingatrefic follicles in M group which maked a great statistical significance(P<0.01) compared with P group. After therapy, the developing and maturefollicles has increased obviously and atrefic follicles has reduced, improving alot in comparision with M group (P<0.01) and making any sense opposed to Pgroup (P>0.05). What was emphasize was that the developing follicles in Wgroup were up apparent than that in P group and H group (P<0.01), but thedistinction of mature follicles and atrefic follicles as well as corpus luteum canbe neglected (P>0.05).
5. Influence on cytokines in ovary: The level of quantitative protein beingencoded of cytokines such as Stem Cell Growth Factor (SCF)、HumanGrowth Differentiation Factor-9(GDF-9) and Bone Morphogenetic Protein-15(BMP-15) has clearly decended opposed to P group, making a statisticalsignificance (P<0.05). Even though the expressin of three cytokines in Wgroup and H group has been evidential up-regulated, the distinct with P groupmake any sense (P>0.05).
6. Effect on the expression of ovarian cell pro-apoptotic gene Bax: Thepositive expression ratio of ovarian cell pro-apoptotic gene Bax in P groupwere manifest lower than the rest, making a statistical significance with Mgroup and W group (P<0.01) but a bit difference compared with H group(P<0.05). The positive expression rate of pro-apoptotic gene Bax in W groupand H group were much lower than that in M group after the therapy. Thoughthe divergence between M group has statistical significance (P<0.01), thedifference between W group and H group can be ignored (P>0.05).
7. Impact on the apoptosis rate of ovarian cell: The apoptosis rate ofovarian cell in P group was at the bottom among all the groups and thedivergence was much evidential compared to the other groups respectively(P<0.01). When the W group ang H group got treated even though theapoptosis rate has descended a lot in comparision with M group (P<0.01) anddifference made no sence between the two groups (P>0.05), there was stillstatistical significance (P<0.01) opposed to P group.
8. Influence on the content of serum Progesterone in peri-implantation:There was no manifest differense among groups. Divergence between Pgroup、H group and W group can be neglected (P>0.05).
9. Effected on the expression of endometrium CT mRNA inperi-implantation: The expression level of endometrium CT mRNA of Wgroup in peri-implantation was the lowest in comparision with P group、Cgroup and H group,making a great statistical significance (P<0.01). Specificly,the expression level of H group was a bit higer than that of P group and Cgroup, but the difference between the three groups maked no sense (P>0.05).
Conclusions:
Professor Shengyang Xu clings to the perspective that it is primary insufficiency of kidney Essence and Qi and partly hepatic stagnation whenmerged with luteal insufficiency based on syndrome differentiation thatcontributes to infertility as the result of DOR and follicle developmentdysfunction. So, he puts forwards the decoction of regulate menstruation forpregnancy promotion, a creative achievement from his perspective which isfocused on nourishing kidney to foster the development of follicle, smoothingliver to improve the function of corpus luteum, and enhancing theendometrium receptivity by strengthening the spleen as the therapy of this disease or supplementary for In Vitro Fertilization And Embryo Transfer(IVF-ET).
This experimental research show that TiaoJingZhuYun decoction canregulate the disordered hormorne level, renovate model rats injured womb andovarian tissue as well as mitigate pathological change of microstructure bymeans of Hypothalamus-Pituitary-Ovary Axis. What’s more, it’s able to fosterthe development of follicle and corpus leteum, reduce the amount of atreficfollicle, accumulate the protein that relevant cytokines in ovarian encodes toregulate the function of model rats autocrine and paracrine as well asjustacrine, depress apoptosis of rats granulosa cells, slacken atrefic follicle toadjust it to cultivate in forward direction. Finally, TiaoJingZhuYun decoctioncan upgrade the expression of endometrium CT mRNA in peri-implantationfor enhancing the endometrium receptivity which can lay the foundation ofembryo implantation.
引文
[1]张玉珍主编.中医妇科学[M].北京:中国中医药出版社,2002:320-322.
[2]乐杰主编.妇产科学[M].北京:人民卫生出版社,2008:351.
[3]丰有吉,沈铿主编.妇产科学[M].北京:人民卫生出版社,2010:394.
[4]刘伟,王丽岩.不明原因不孕患者小卵泡排卵的诊治意义[J].中华妇幼临床医学杂志(电子版),2007,4(3):94-95.
[5]赵得雄.小卵泡排卵不孕及习惯性流产患者的临床诊治研究[J].中国妇幼保健,2010,25:217-218.
[6]赵秀萍.小卵泡排卵中医证候学调查及分析[D].北京:北京中医药大学,2011.
[7]丰有吉,沈铿主编.妇产科学[M].北京:人民卫生出版社,2010:24.
[8]韩玉芬,程淑蕊,敬文娜,等.卵巢储备功能下降的预测及治疗[J].中国计划生育学杂志,2007,2:117.
[9]李焱,陈闯.雌孕激素序贯治疗卵巢功能低下的临床观察[J].中国医药指南,2012,2(10):113-114.
[10]连方,陈艳花.中西医结合改善卵巢储备的研究[C].全国中西医结合围绝经期专题学术会议论文集,2010:36-37.
[11]王素荣,李辉杰.人工周期治疗60例卵巢储备功能低下的体会[J].现代医药卫生,2011,27(4):566-567.
[12]Tarlatzis BC, Zeoiridis L, Grimbizis G, et al. Clinical management ofovarian response to stimulation for IVF: a systematic review[J]. HumReprod Update.,2003,9(1):61-76.
[13]Ubaldi FM, Rienzi L, Ferrero S, et al. Management of poor responders inIVF[J]. Reprod Biomed Online.,2005,10(3):235-246.
[14]Ana Claver o, Jose A Castillab, Ana I Nunez. Apoptosis in humangranulose cells after induction of ovulation in women participating in anintracytoplasmic sperm injection program[J]. Obstetrics&Gynecologyand Reproductive Biology,2003,110:181-185.
[15]王增艳,何方方.空卵泡综合征研究进展[J].生殖医学杂志,2006,15(5):357-360.
[16]Reichman DE, Hornstein MD, Jackson KV, et al. Empty folliclesyndrome-does repeat administration of hCG really work?[J]. Fertil Steril.,2010,94(1):375-377.
[17]龙兴宇.控制性超排卵中过早黄素化对体外受精影响妊娠结局及分子机制的初步研究[D].长沙:中南大学,2009.
[18]Thomas K, Thomson AJ, Wood SJ, et al. Endometrial integrin expressionin women undergoing IVF and ICSI: a comparison of the two groups andfertile[J]. Hum Reprod.,2003,18(2):364-369.
[19]Mirkin S, Nikas G, Hsim JG, et al. Gene expression profiles and endstructural/functional features of the pri-implantation endometrium innature and gonadotropin-simulated cycles[J]. Clin Endocrinol Metab.,2004,89(11):5742-5752.
[20]Massai MR, Ziegler D, Bergeron C, et al. Clomiphene citrate affectscervical mucus and endometrial morphology independently of the changesin Plasma hormonal levels induced by multiple follicular recruitment[J].Fertil Steril.,1993,59(6):1179.
[21]章辉.排卵障碍性不孕症中医临床症候分布规律的研究[D].广州:广州中医药大学,2008.
[22]周剑平.中药加克罗米芬治疗排卵功能障碍性不孕的临床观察[J].浙江中医药大学学报,2006,30(3):255-256.
[23]曹泽毅主编.中华妇产科学[M].北京:人民卫生出版社,1999:2200-2201.
[24]罗元恺.罗元恺论医集[M].北京:人民卫生出版社,1990:7.
[25]史广宇,单书剑主编.不孕专辑[M].北京:中医古籍出版社,1992:1-10.
[26]徐升阳,王克林,贺漪,等主编.徐升阳妇科医著选编[M].北京:中医古籍出版社,2005:104-108.
[27]李宝顺主编.名医名录[M].北京:中医古籍出版社,1993,3:396-401.
[28]徐琳,曾春晖.徐升阳辨证治疗不孕症复杂案例4则[J].世界中医药杂志,2011,6(1):57-59.
[29]徐琳,徐升阳. IVF-ET助孕失败后服中药再次移植20例结局分析[J].中西医结合研究,2012,4(2):17-18.
[30]王静,李红梅,徐琳.徐升阳主任医师治疗不孕症经验[J].新中医,2012,44(9):146-147.
[31]刘雯雯.徐升阳教授经验方补肾助孕丸对肾虚型不孕患者助排卵的临床观查[J].中国营养保健,2012,5(5):149.
[1]张玉珍主编.中医妇科学[M].北京:中国中医药出版社,2002:364.
[2]丰有吉,沈铿主编.妇产科学[M].北京:人民卫生出版社,2010:21.
[3]陈静,阮详燕.65例育龄妇女卵巢储备功能下降的临床研究分[J].医学综述,2011,4(17):1253.
[4]Sun W, Stegmann BJ, Henne M, et al. A new approach to ovarian reservetesting[J]. Fertil Steril.,2008,90(6):2196-2202.
[5]Maheshwari A, Fowler P, Bhattacharya S. Assessment of ovarian reserveshould we perform tests of ovarian reserve routinely?[J]. Hum Reprod.,2006,21(11):2729-2735.
[6]Templeton A, Morris JK, Parslow W. Factors that affect outcome of in-vitrofertilisation treatment[J]. Lancet.,1996,348(9039):1402-1406.
[7]马灵芝,李爽,夏天.卵巢储备力降低的监测[J].现代中西医结合杂志,2010,19(11):1425-1427.
[8]曹泽毅主编.中华妇产科学[M].北京:人民卫生出版社,1999:2138-2139.
[9]张吟,许小凤,毛菲.卵巢储备功能下降的病因病机初探[J].黑龙江中医药,2009,4:3.
[10]许小凤,谈勇,陈宣伊.卵巢储备功能下降中医辨证思路和优势[J].中国中医药信息杂志,2009,16(12):88-89.
[11]许小凤,谈勇,薛晓明,等.血清抑制素B水平预测卵巢储备功能的临床价值[J].现代妇产科进展,2008,17(8):568-570．
[12]de Taraciuk MB, Nolting M, Fernandez G, et al. Psychological assessmentof patients with premature ovarian failure[J]. Gynecol Endoerinol.,2008,24(1):45-53.
[13]陈和利,金石,王力,等.知识女性月经失调与精神因素关系调查[J].江西中医学院学报,2007,19(3):86-88.
[14]马丽灵,阮祥燕.100例卵巢早衰相关因素的调查分析[J].实用妇产科杂志,2009,25(4):212-215.
[15]Matikainen T, Perez Gl, Jurisicova A, et al. Aromatic hydrocarbonreceptor-driven Bax gene expression is required for premature ovarianfailure biohazardous environmental chemicals[J]. Nat Genet.,2001,28(4):355-360.
[16]尹薇薇.卵巢储备功能下降女性的生存质量及中医体质类型的研究[D].广州:广州中医药大学,2011.
[17]Ennis S, Ward D, Murray A. Nonlinear association between CGG repeatnumber and age of menopause in FMR1premutation carriers [J]. Eur JHum Genet.,2006,14(2):253-255.
[18]Rao L, Babu A, Padmalatha V, et al. Novel X-chromosomal defectassociated with abnormal ovarian function[J]. J Obstet Gynaecol Res.,2005,31(l):12-15.
[19]Kok H S, van Asselt K M, van der Schouw Y T, et al. Genetic studies toidentify genes underlying menopausal age[J]. Human reproduction update,2005,11(5):483-493.
[20]Steiner AZ, Baird DD, Kesner JS. Mother's menopausal age is associatedwith her daughter's early follicular phase urinary follicle-stimulatinghormone level[J]. Menopause,2008,15(5):940-944.
[21]Kamada M, Daitoh T, Mori K, et al. Etiological implication ofautoantibodies to zona pellucida in human female infertility[J]. Am JReprod Immunol.,1992,28:104.
[22]马张,孔北华,邓晓惠.抗卵巢抗体对体外受精-胚胎移植过程及结局的影响[J].现代妇产科进展,2004,13(6):453.
[23]Bagavant H, Adams S, Terranova P, et al. Autoimmune ovarianinflammation triggered by proinflammatory (Th1) T cells is compatiblewith normal ovarian function in mice[J]. Biol Reprod.,1999,61(3):635-642.
[24]Chen S, Sawicka J, Betterle C, et al. Autoantibodies to steroidogenicenzymes in autoimmune polyglandular syndrome, Addison's disease, andpremature ovarian failure[J]. J Clin Endocrinol Metab.,1996,81(3):1871-1876.
[25]Russel P. The clinicopathological features of primary ovarian failure [J].Verh Dtsch Ges Pathol.,1997,81:197-209.
[26]Ghersevich S, Isomaa V, Vihko P. Cytokine regulation of the expression ofestrogenic biosynthetic enzymes in cultured rat granulosa cells[J]. MolCell Endocrinol.,2001,172(1-2):21-30.
[27]王一峰,欧汝强,杨宁,等.卵巢早衰患者血清抗透明带抗体和肿瘤坏死因子-α, γ-干扰素及白细胞介素-2的分析[J].生殖医学,2002,11(1):7-10.
[28]蒋利华,姚珍薇,张新华,等.卵巢早衰危险因素的病例对照研究[J].重庆医科大学学报,2006,31(3):424-425.
[29]Barbarino-Monnier P, Gobert B, Guillet-Rosso F, et a1. Antiovaryantibodies, repeated attempts,and outcome of in vitro fertilization [J].Fertil and Steril.,1991,56:289.
[30]黄邱朝,王国洪,赵技文,等.不孕症妇女抗卵巢抗体与血清激素水平的关系[J].上海医学,1997,20(6):573.
[31]Tuohy VK, Altuntas CZ. Autoimmunity and premature ovarian failure[J].Curr Opin Obstet Gynecol.,2007,19(4):366.
[32]Laissue P, Lakhal B, Benayoun BA, et al. Functional evidence implicatingFOXL2in non-syndromic premature ovarian failure and in the regulationof the transcription factor OSR2[J]. Med Genet.,2009,46(7):455-457.
[33]Hviid A, Rubin S, Mühlemann K. Mumps[J]. Lancet.,2008,37(l):932-944.
[34]薛艳军,罗新.卵巢子宫内膜异位囊肿剔除术中的机械损伤和热损伤对卵巢储备的影响[J].广东医学,2008,29(5):720-721.
[35]刘萍,孙丽,全松.腹腔镜卵巢囊肿剥除术对卵巢储备功能及体外受精-胚胎移植的影响[J].广东医学,2009,30(6):950-952.
[36]于传鑫.实用妇科内分泌学[M].第二版.上海:复旦大学出版社,2004:100.
[37]丰有吉主编.妇产科学[M].北京:人民卫生出版社,2002:345.
[38]丁曼琳.妇产科疾病诊断与鉴别诊断[M].第二版.北京:人民卫生出版社,1999:357.
[39]赵明霞,王丽红,孙银婷,等.血清抑制素B,窦卵泡数预测高龄不育妇女卵巢储备功能的临床研究[J].中国医学文摘(计划生育妇产科学),2008,27(6):411-413.
[40]Klinkert ER, Broekmans FJ, Looman CW, et al. Expected poor responderson the basis of an antral follicle count do not benefit from a higher startingdose of gonadotrophins in IVF treatment:a randomized controlled trial[J].Hum Reprod.,2005,20(3):611-615.
[41]饶玉梅.不孕不育妇女卵巢储备功能的检测[J].中国优生与遗传杂志,2003,11(2):143.
[42]Zaidi J, Barber J, Kyei-Mensah A, et al.Relationship of ovarian stromalblood flow at the baseline ultrasound scan to subsequent follicularresponse in an in vitro fertilization program[J]. Obstet Gynecol.,1996,88:779.
[43]Kupesic S, Kurjak A, Bjelos D, et al. Three-dimensionalultrasonographic ovarian measurements and in vitro fertilization outcomeare related to age[J]. Fertile Steril.,2003,79(1):190-197.
[44]Sharara FI, MaClamrock HD. The effect of aging on ovarian volumemeasurements in infertile women[J]. Obstet Gynecol.,1999,94(11):57-60.
[45]Tepper R, Zalel Y, Markov S, et al. Ovarian volume in postmenopausalwomen--suggestions to an ovarian size nomogram for menopausal age[J].Aeta Obstet Gyneeol Scand.,1995,74:208-211.
[46]Smotrich DB, Widra EA, Gindoff PR, et al. Prognostic value of day3estradiol on in vitro fertilization outcome[J]. Fertil Steril.,1995,64:1136-1140.
[47]Hall JE, Welt CK, Cramer DW. Inhibin A and inhibin B reflect ovarianfunction in assisted reproduction but are less useful at predictingoutcome[J]. Hum Reprod.,1999,14:409-415.
[48]吴日然,廖月蝉,叶云,等.测定血清抑制素B水平预测卵巢储备力及调节控制性超排卵用药的研究[J].中华妇产科杂志,2005,40(10):679-681.
[49]陈士岭.卵巢储备功能的评价[J].国际生殖健康/计划生育杂志,2009,28(9):283.
[50]Gürbüz B, Yalti S, Ficicioglu C, et a1. The relation of serum and follicularfluid leptin and ovarian steroid levels in response to induction of ovulationin in vitro fertilization cycles[J]. European Journal of Obstetrics&Gynecology and Reproductive Biology,2005,118:214-218.
[51]雷纯钢,刘小敏.卵巢储备功能的评价[J].右江民族医学院学报,2008,1:139-141.
[52]邓远征,李凤玲.补肾疏肝活血法治疗卵巢储备功能下降的临床观察[J].内蒙古中医药,2012,1:31.
[53]李焱,陈闯.雌孕激素序贯治疗卵巢功能低下的临床观察[J].中国医药指南,2012,10(2):113-114.
[54]Gleicher N1, Weghofer A, Barad DH. Improvement in diminished ovarianreserve after dehydroepiandrosterone supplementation[J]. ReproductiveBioMedicine Online,2010,21:360-365．
[55]Barad D, Gleicher N. Effect of dehydroepiandrosterone on oocyte andembryo yields, embryo grade and cell number in IVF[J]. HumanReproduction,2006,21(11):2845-2849．
[56]陈新娜. DHEA和卵巢功能低下1例及文献复习[J].现代妇产科进展,2010(9):715-715.
[57]徐千花,曹云霞,魏兆莲.促性腺激素释放激素抑制剂在卵巢功能低下患者促排卵中的应用[J].中国妇幼保健,2008,23:3883-3885.
[58]Tesarik J, Hazout A, Mendoza C. Improvement of delivery and live birthrates after ICSI in women aged>40years by ovarian co-stimulation withgrowth hormone[J]. Human Reproduction,2005,20(9):2536-2541.
[59]丁国莲,黄荷凤.生长激素在辅助生殖技术中的应用及作用机制[J].国际生殖健康/计划生育杂志,2008,6:007.
[60]宋慧玲.生长激素对卵巢储备功能低下患者IVF-ET治疗结局的影响[D].郑州:郑州大学,2011.
[1]许小凤,谈勇,陈宣伊.卵巢储备功能下降中医证治思路和优势[J].中国中医药信息杂志,2009,16(12):88-89.
[2]李淑萍.滋肾疏肝法治疗卵巢储备功能下降35例疗效观察[J].四川中医,2004,12(2):62-63.
[3]杨胜华.滋肾育胎丸对卵巢储备功能下降患者卵巢功能的影响[D].广州:广州中医药大学,2012.
[4]苍荣,夏天,王宝娟.韩冰运用补肾调冲方治卵巢储备功能下降性不孕症经验[J].江西中医药,2012,1(1):15-16.
[5]王琳.补肾益天癸提高高龄不孕妇女卵巢反应性的临床研究[D].济南:山东中医药大学,2002.
[6]徐眠,司徒仪,李丽芸,等.中医补肾法对高龄不孕妇女的卵巢储备功能的调控[J].广州中医药大学学报,2004,21(7):267-270.
[7]阮怀玲.中药周期疗法对卵巢储备功能降低者的临床疗效观察[D].广州:广州中医药大学,2011.
[8]陈益昀.艾灸结合中药治疗卵巢功能早衰临床观察[J].山西中医,2010,26(5):29-30.
[9]张迎春,李芳园,李兰荣,等.针药对卵巢储备功能影响的临床研究[J].四川中医,2010,28(2):103-104.
[10]潘芳,俞瑾.中西医结合治疗卵巢功能低下性不孕症48例临床观察[C].全国第八次中医妇科学术研讨会论文汇编,2008:112-114.
[11]连方,张建伟,张宁,等.中西医结合疗法在试管婴儿技术中的应用[J].山东中医药大学学报,2002,26(3):182-183.
[1]邹移海,徐志伟,苏钢强.实验动物学[M].北京:科学出版社,2004:84.
[2]曹俊岩.雷公藤多苷致大鼠卵泡发育障碍模型的中医证候属性研究[D].成都:成都中医药大学,2011.
[3]付丽.雷公藤多苷致大鼠卵巢功能低下模型的病理机制与中医证候属性研究[D].成都:成都中医药大学,2010.
[4]谌婕,吴克明,王家葵,等.雷公藤多甙致雌性小鼠肾虚生殖功能低下动物模型的研究[J].中药新药与临床药理,2007,18(3):208-211.
[5]张黎鹏.雷公藤多甙致雌性小鼠肾虚生殖功能低下模型的复制及机理探讨[D].成都:成都中医药大学,2007.
[6]张黎鹏.雷公藤多甙致雌性小鼠生殖功能低下模型证候初探[J].福建中医药,2007,4(2):43.
[7]曹俊岩,范宏元,曾莉,等.从细胞因子研究雷公藤多苷致大鼠卵巢功能低下模型的中医证候属性[J].辽宁中医杂志,2012,39(11):2282-2283.
[8]倪张俊.雷公藤致大鼠药源性卵巢功能耗损模型建构与补肾法干预研究[D].广州:广州中医药大学,2013.
[9]高慧,杨涓,韩冰,等.药物性卵巢早衰动物模型的研究[J].国医论坛,2007,22(3):22-25.
[10]钱绍帧.雷公藤的药理及抗生育作用[J].江苏医药,1987,13(12):646-649.
[11]乔子红.雷公藤抗生育作用的临床及实验研究概况[J].中级医刊,1990,25(2):70-72.
[12]高玉平,陈德甫,朱建善,等.雷公藤多苷对子宫肌瘤组织及肌组织ER和PR表达的影响[J].上海第二医科大学学报,2003,23(1):50.
[13]谷春霞,陶学廉,葛秦生,等.雷公藤多苷致闭经原因探讨[J].中国医学科学院学报,1989,11(2):151.
[14]王世间.卵巢疾病[M].北京:人民卫生出版社,2004:102-114.
[1]郑家润,刘季和,徐兰芳,等.雷公藤总甙的毒性研究[J].中国医学科学院学报,1983,5(2):73-78.
[2]赵柳霞.雷公藤多甙治疗子宫肌瘤64例[J].中国中西医结合杂志,2003,23(10):787-788.
[4]徐叔云,卞如濂,陈修.药理实验方法学[M].北京:人民卫生出版社,2006:202-204.
[5]王瑞峰,郝丽,潘美华,等.雌孕激素替代治疗雷公藤多甙致雌性大鼠生殖系统损害的实验研究[J].中国医科大学学报,2008,4:198.
[6]姜娇娇.雷公藤多甙及雌孕激素治疗对大鼠卵巢Bcl-2和Bax表达的实验研究[D].合肥:安徽医科大学,2010.
[7]陈奇.中药药理实验方法[M].北京:人民卫生出版社,1994:206.
[8]张建民主编.卵巢病理学[M].南昌:江西科学技术出版社,2006:6-18.
[9]陈乐真主编.妇产科诊断病理学[M].北京:人民军医出版社,2002:261-263.
[10]林科雄,王长征,钱桂生.雷公藤甲素对诱导CD4+、 CD8+T细胞凋亡的作用[J].免疫学杂志,2000,6(l):24-26.
[11]Tilly JL, Kowalski KI, Johnson AL, et al. Involvement of apoptosis inovarian follicular atresia and postovulatory regression[J]. Endocrinology,1991,129(5):2799-2801.
[12]Fanchin R, Schon uer LM, Righini C, et al. Serum anti-Müllerianhormone dynamics during controlled ovarian hyperstimulation[J]. HumReprod.,2003,18(2):328.
[13]庄广伦,李轶,梁晓燕.诱导排卵适应证与方案的应用专题讨论[J].实用妇产科杂志,2007,23(3):131.
[14]徐珉,司徒仪,李丽芸,等.中医补肾法对高龄不孕妇女的卵巢储备功能的调控[J].广州中医药大学学报,2004,21(4):267-271.
[15]李军,王翠霞,陈莹,等.补肾复方延缓雌性大鼠卵巢早衰的实验研究[J].辽宁中医杂志,2007,34(5):681-683.
[16]张树成,沈明秀,蔡连香,等.补肾调经和养血补肾方药调经促排卵作用的实验研究[J].中医杂志,1999,40(6):369.
[17]高慧,杨涓,夏天,等.补肾调冲方对卵巢早衰人鼠性激素水平和卵巢组织形态学的影响[J].国医论坛,2008,23(1):35-39.
[18]陆华,刘敏如,李养梅.养精汤促卵泡发育的临床观察[J].中国中西医结合杂志,1998,18(4):217.
[19]谈勇,石川睦男.补肾调周法在体外受精-胚移植期前应用的临床观察[J].中国中医药信息杂志,2001,12(12):45-46.
[20]李仪奎.中药药理实验方法学[M].上海:上海科学技术出版社,1991:224.
[21]Aisen PS, Berg JD, Craft S, et al. Steroid-induced elevation of glucose in Alzheimer's disease: relationship to gender,apolipoprotein E genotype and cognition[J]. Psychoneuroendocrinology,2003,1:113-120.
[22]单志群,葛蕾.补肾调冲药诱发排卵的实验研究[J].深圳中西医结合杂志,1998,8(1):11-13.
[23]李伊然.雌激素及其受体与卵母细胞成熟的相关性[D].西宁:宁夏医科大学,2013.
[24]岳占碰,张学明,马琳.雌激素对哺乳动物卵泡发育影响的研究进展[J].中国畜牧杂志,2007,43(1):41-43.
[25]Homburg R. Clomiphene citrate-end of an era? A mini-review[J]. HumReprod.,2005,20:2043-2051.
[26]郭玉琪,张展,刘义,等.克罗米芬对子宫内膜发育的影响[J].生殖医学杂志,2006,15(4):129.
[27]Unfer V, Costabile L, Gerli S,e t al. Low does of ethinyl estradiol canreverse the antiestrogenic effets of clomiphene citrate on endometrium[J].Gynecol Obstet Invest.,2001,51(2):120-123.
[28]石红.卵巢旁分泌与自分泌[J].中国实用妇科与产科杂志,2001,17(4):241-243.
[29]许爱霞,汪雁,徐良全,等.卵泡发育中相关基因的调控[J].生殖与避孕,2008,28(12):745-750.
[30]严杰,乔杰.干细胞因子及其受体在卵泡早期发育中的作用[J].生殖与避孕,2008,12(12):739-743.
[31]洪俊君,王子玉,王锋,等.干细胞因子在卵泡发育过程中的作用[J].细胞生物学杂志,2008,28:667-670.
[32]赵海波,何亚绒,李爱莉,等.卵泡液干细胞因子水平对卵母细胞发育、受精和卵裂影响的实验研究[J].中国计划生育学杂志,2006,130(8):475-476.
[33]Jin X, Han CS, Zhang XS, et al. Signal transduction of stem cell factor inpromoting early follicle development[J]. Mol Cell Endocrinol.,2005,229(1-2):3-10.
[34]王桂红,赵海波,辛晓燕.人卵泡液中干细胞因子水平及其对卵泡发育的影响[J].第四军医大学学报,2003,24(6):543-545.
[35]常秀峰.补肾调经方对IVF-ET妊娠结局及颗粒细胞凋亡和OSFs的影响[D].石家庄:河北医科大学,2011.
[36]于晓娜.骨形态发生蛋白15基因与人类卵母细胞及卵泡发育[J].国际生殖健康/计划生育杂志,2008,27(7):215-217.
[37]Thomas FH, Vanderhyden BC. Oocyte-granulosa cell interactions duringmouse follicular development: regulation of kit ligand expression and itsrole in oocyte growth[J]. Reprod Biol Endocrinol.,2006,4:19.
[38]李爽,夏阳,夏天.补肾调冲方对半乳糖致POF大鼠始基卵泡募集及卵泡闭锁相关因子GDF-9表达的影响[J].辽宁中医杂志,2011,38(11):2267-2270.
[39]苗竹林,王自能,郑佩娥,等.生长分化因子-9在大鼠卵巢中的表达[J].暨南大学学报(医学版),2005:195-198.
[40]Chauhan P, Sodhi A, Tarang S. Cisplatin-treated murine peritonealmacrophages induce apoptosis in L929cells: role of Fas-Fas ligand andtumor necrosis factor-tumor necrosis factor receptor1[J]. Anticancer Drug,2007,18(2):187-196.
[41]李键.生长分化因子9在卵泡发育中的调控作用[J].国际生殖健康/计划生育杂志,2008,27(2):84.
[42]张树成,沈明秀,蔡连香,等.补肾调经和养血补肾方药调经促排卵作用的实验研究[J].中医杂志,1999,40(6):369.
[43]杨桂云,王佩娟,贾晓斌,等.“补肾活血汤”对小鼠早期胚胎发育的作用[J].江苏中医,2000,21(11):40.
[44]Shetty G, Krishnamurthy H, Krishnamurthy HN, et al. Effect of estrogendeprivation on the reproductive physiology of male and female primates[J].J Steroid Biochem Mol Biol.,1997,61(3-6):157-166.
[45]郭鹊晖,郑志群.来曲唑的促排卵及胚胎毒性的研究进展[J].生殖与避孕,2009,29(2):120-124.
[46]耿蔷,郭遂群,全松,等.来曲唑用于促排卵对卵泡发育和子宫内膜影响的临床观察[J].实用医学杂志,2010,26(12):2209-2211.
[1]Exley GE, Tang C, McElhinny AS, et a1. Expression of caspase and BCL-2apoptotic family members in mouse preimplantation embryos[J]. BiolReprod.,1999,61(1):231-239.
[2]Jurisicova A, Antenos M, Varmuza S, et al. Expression of apoptosis-relatedgenes during human preimplantation embryo development: potential rolesfor the Harakiri gene product and Caspase-3in blastomere fragmentation[J].Mol Hum Reprod.,2003,9(3):133-141.
[3]Reed JC. Bcl-2and the regulation of programmed cell death[J]. J Cell Biol.,1994,124(1-2): l-6.
[4]Kugu K, Ratts VS, Piquette GN, et al. Analysis of apoptosis and expressionof bcl-2gene family members in the human and baboon ovary[J]. CellDeath Differ.,1998,5:67-76.
[5]刘岚,王元佩,施作霖,等.黄体功能不全患者月经子宫内膜中雌孕激素受体、细胞凋亡及bcl-2、bax蛋白的表达[J].中华妇产科杂志,2002,37(1):47-48.
[6]吴际,张丽珠,李潭,等.性激素对人卵巢颗粒细胞凋亡的作用[J].中华妇产科杂志,1998,33(3):157-159.
[7]蔡泽骏.性激素对大鼠卵巢颗粒细胞凋亡基因表达的作用[J].海峡药学,2002,14(6):22-23.
[8]秦佳佳,李瑞满.坤宁安对为绝经期大鼠卵巢颗粒细胞凋亡相关因子Bax及Bax mRNA的影响[J].湖南中医学院学报,2006,26(3):23-24.
[9]许小凤,谈勇,江国荣,等.补肾填精中药干预雷公藤多甙致卵巢储备下降大鼠卵巢功能的实验研究[J].中国中医基础医学杂志,2011,11(7):1225-1227.
[10]苗小芬,许小凤,陈宣伊,等.补肾活血组方对大鼠卵巢颗粒细胞的作用[J].苏州大学学报(医学版),2010,30(4):741-747.
[11]许小凤,谈勇,陈宣伊,等.补肾活血中药对雷公藤致卵巢储备下降大鼠颗粒细胞凋亡的影响[J].医学研究杂志,2009,38(12):123-125.
[12]孙海芸,陈云芝,薛晓鸥,等.四物合剂对化疗后大鼠卵巢形态及颗粒细胞凋亡的影响[J].中国实验方剂学杂志,2012,18(5):257-259.
[1]Lin HY, Harris TL, Flannery MS, et al. Expression cloing of an adenylatecyclase-coupled calcitonin receptor[J]. Science,1991,254:1022.
[2]Means AR, VanBerkum MF, Bagehi I, et al. Regulatory function ofcalmodulin[J]. Pharmacol Ther.,1991,50:225-270.
[3]Ding YQ, Zhu LJ, Bagchi MK, et al. Progesterone stimulates calcitoningene expression in the uterus during implantation [J]. Endoerinology,1994,135:2265.
[4]Koji Yoshinaga. Endocrinology of Embryo-Endometrium Interactions[M].New York: Plenum Press,1994:391-392.
[5]张艳萍,武玉玲,邴鲁军,等.降钙素受体在小鼠早期胚胎及围植入期子宫内膜的表达[J].山东大学学报,2005,12:1105-1106.
[6]冉雪梦,张华,邰国香,等.毓麟珠加减方对促排卵后子宫内膜CTmRNA表达的影响[J].中医研究,2007,2:29-31
[7]付志红,陈士岭,邢福祺.降钙素对人类胚胎着床的影响[J].中华妇产科杂志,2002,37(1):184.
[8]Carson DD, Bagchi I, Dey SK, et al. Embryo implantation[J]. Dev Biol.,2000,223(2):217-237.
[9]王伟,刘栋,王秀萍.降钙素对胚胎着床的影响机理[J].生物技术通报,2007,2:44-46.
[10]谢晓鹰,杨纫姝,毛伟平.钙调素拮抗剂与细胞内Ca2+浓度对人蜕膜细胞活力的影响[J].动物学报,1999,45(1):80-87.
[11]Zhu LJ, Cullinan-Bove K, Polihronis M, et al. Calcitonin is aprogesterone-regulated marker that forecasts the receptive state ofendometrium during implantation[J]. Endocrinology,1998,139(9):3923-3934.
[12]陆楠,高英茂,李少玲.大鼠胚泡植入过程中子宫内膜降钙素的动态表达及其与血清雌、孕激素水平的关系[J].生殖医学杂志,2004,6(3):158-162.
[13]郭艺红.白血病抑制因子、胞饮突与子宫内膜容受性关系的实验研究[D].郑州:郑州大学,2006.
[14]孙振高.补肾中药对超排卵周期子宫内膜容受性及整合素β3/骨桥蛋白时序表达的影响[D].济南:山东中医药大学,2009.
[15]陈海燕.黄体功能不全的病因、诊断和治疗[J].医学综述,1999,5(6):256-259.
[16]汪宏波,占海英,李红发.黄体功能不全患者着床期子宫内膜雌孕激素受体的表达及超微结构改变[J].中国妇幼保健,2009,12:44-49.
[17]张华,冉雪梦,陈芊,等.补肾活血方增强子宫内膜降钙素基因表达的临床研究[J].中国计划生育学杂志,2007,2:171-173.
[18]曹蕾,罗颂平,欧汝强.补肾健脾中药复方对肾虚模型大鼠子宫内膜容受性的影响[J].中华中医药杂志,2011,26(5):1057-1061.
[19]邓伟民,赵彦鹏,葛明晓,等.益气血补肝肾中药对体外受精-胚胎移植临床结局的影响[J].辽宁中医药大学学报,2011,13(6):5-7.
[20]曹蕾,罗颂平,欧汝强,等.补肾健脾法对复发性流产患者子宫内膜容受性的干预作用[J].广州中医药大学学报,2010,27(11):562-565.
[1]徐升阳,王克林,贺漪,等主编.徐升阳妇科医著选编[M].北京:中医古籍出版社,2005:104-108.
[2]罗元恺.罗元恺论医集[M].北京:人民卫生出版社,1990:7.
[3]史广宇,单书剑主编.不孕专辑[M].北京:中医古籍出版社,1992:1-10.
[4]许金晶,吴育宁.阴虚体质与卵巢储备功能下降[J].中华中医药杂志,2012,27(6):1621-1623.
[5]张荣,邓伟民.卵巢低反应患者中医症候分布研究[J].辽宁中医药大学学报,2013,15(11):98-100.
[6]王静,李红梅,徐琳.徐升阳主任医师治疗不孕症经验[J].新中医,2012,9:146-147.
[7]刘雯雯.徐升阳教授经验方补肾助孕丸对肾虚型不孕患者助排卵的临床观查[J].中国营养保健,2012,5(5):149.
[8]徐琳,曾春晖.徐升阳辨证治疗不孕症复杂案例4则[J].世界中医药杂志,2011,6(1):57-59.
[1]叶海涌.淫羊藿苷及其拟代谢产物的雌激素样作用体外研究[D].杭州:浙江大学,2004.
[2]赵丕文,牛建昭,王继峰,等.6种中药活性成分植物雌激素作用的比较研究[J].中国药学杂志,2007,42(12):1852-1855.
[3]陈颐.补肾活血方改善GnRHa诱发低雌激素状态的疗效观察[D].广州:广州中医药大学,2011.
[4]巴文君,孙丽萍,张秋菊,等.补骨脂对初老小鼠体内雌孕激素水平作用实验研究[J].中医药学报,2010,5:19-21.
[5]郝庆秀,王继峰,牛建昭,等.熟地等4味中药的植物雌激素作用的实验研究[J].中国中药杂志,2009,3(5):620-623.
[6]牛建昭.十种中药植物雌激素样作用及其机制的研究[D].北京:北京中医药大学,2009.
[7]Fan GW, Gao XM, Wang H, et al. The anti-inflammatory activities ofTanshinone IIA, an active component of TCM, are mediated by estrogenreceptor activation and inhibition of iNOS[J]. J Steroid Biochem Mol Biol.,2009,113(3/5):275-280.
[8]陶仕英.二仙汤及活性成分植物雌激素样作用机制研究[D].北京:北京中医药大学,2011.
[9]赵洁,侯连兵.植物雌激素的活性成分及其生物活性研究进展[J].中药材,2005,5(5):524-526.
[10]康建颖.植物雌激素的研究进展以及在妇科领域的应用概况[D].成都:成都中医药大学,2006.
[11]Younis JS, Skournik A, Radin O, et al. Poor oocyte retrieval is amanifestation of low ovarian reserve[J]. Fertil Steril.,2005,83(2):504-507.
[12]Duru NK, Cincik M, Dede M, et al. Retrieval of zona-free immatureoocytes in a woman with recurrent empty follicle syndrome: a casereport[J]. J Reprod Med.,2007,52(9):858-863.
[13]李承慈.植物雌激素的探讨[J].国外医学计划生育分册,2000,19(5):87-90.
[14]李培旭,李尚为,彭芝兰,等.超排卵对小鼠卵母细胞和胚胎发育潜能的影响[J].四川大学学报(医学版),2007,38(4):725-727.
[15]郭新宇,李海霞,谢妍,等.自然排卵,促排卵和超促排卵状态下小鼠卵巢组织中生长分化因子-9(GDF-9)的表达[J].生殖与避孕,2013,33(001):1-5.
[16]邱冉冉.护卵汤对GnRHa超排卵大鼠卵巢超微结构及体细胞凋亡的影响[D].长沙:湖南中医药大学,2013.
[17]申可佳.护卵汤对GnRHa超排卵大鼠卵泡发育的影响研究[D].长沙:湖南中医药大学,2012.
[18]Sifer C, Blanc-Layrac G, Bringuier AF, et al. Effects of aGonadotropin-Releasing Hormone agonist and Follicle StimulatingHormone on the incidence of apoptosis in human luteinized granulosacells[J]. Eur J Obstet Gynecol Reprod Biol.,2003,110(1):43-48.
[19]Otsuka F, Shimasaki S. A negative feedback system between oocyte bonemorphogenetic protein15and granulosa cell kit ligand: its role inregulating granulosa cell mitosis[J]. Proc Natl Acad Sci USA.,2002,999(12):8060-8065.
[20]Clavero A, Castilla JA, Nú ez AI, et al. Apoptosis in human granulosacells after induction of ovulation in women participating in anintracytoplasmic sperm injection program[J]. Obstetrics&Gynecologyand Reproductive Biology,2003,110:181-185.
[21]Kaneko T, Saito H, Takahashi T, et al.Effects of controlled ovarianhyperstimulation on oocyte quality in terms of the incidence of apoptoticgranulosa cells[J]. J Assist Reprod Genet.,2000,17(10):580-585.
[22]Hutt KJ, McLaughlin EA, Holland MK. Kit ligand and c-Kit have diverseroles during mammalian oogenesis and folliculogenesis[J]. Mol HumReprod.,2006,12(2):61-69.
[23]辛明蔚,李玛建,何军琴.中医药在体外授精-胚胎移植中的应用思路[J].安徽中医学院学报,2004,29(4):31-33.
[24]申可佳,尤昭玲.中医药改善超排卵周期卵泡发育的研究思路[J].湖南中医药大学学报,2012,32(4):3-5.
[25]金方.何嘉琳谈在辅助生育技术中中医药的应用[J].北京中医,2004,23(6):329.
[26]傅萍,楼毅云.中医药在体外受精-胚胎移植技术中的辨治思路[J].中华中医药学刊,2009,27(9):1870-1873.
[27]连方.中医药在生殖领域的研究[C].国际生殖医学新技术研讨会资料汇编,2011.
[28]杨海虹,高宝辉,金慧佩.小剂量雌激素对诱导排卵增殖期子宫内膜的影响[J].中国妇幼保健,2005,20(15):1447-1449.
[29]郭秋琼,高飞雁.小剂量雌激素对克罗米芬诱导排卵增殖期子宫内膜的影响[J].实用临床医学,2006,7(4):89-91.
[30]芦小娟.戊酸雌二醇对克罗米芬周期中子宫、生殖激素及妊娠率的影响[D].西安:第四军医大学,2003.
[31]程宽,冷维春,焦晓光.氯米芬加雌激素对子宫内膜雌孕激素受体影响的临床观察[J].中国妇幼保健,2005,20(5):625-626.
[32]秦丽洁,韩英林,于小予,等.氯米芬加倍美力对子宫内膜雌孕激素受体影响的临床观察[J].中国妇幼保健,2005,20(22):2931-2932.
[33]李春,黄朝霞,程静,等.不同雌激素对克罗米芬促排卵周期子宫内膜、子宫动脉血流及临床妊娠率的影响[J].中国妇幼保健,2007,22(36):5195-5197.
[34]谭晓珊,秦娟,谭兵兵.小剂量阿司匹林对薄型子宫内膜发育的影响[J].中国综合临床,2006,22:29-31.
[35]杨海虹,叶碧绿,吕杰强,等.氯米芬合用阿司匹林对子宫内膜发育和子宫血流的影响[J].实用妇产科杂志,2005,2;21(2):114-115.
[36]李宝兰.天然雌激素加小剂量阿司匹林对促排卵子宫内膜发育60例临床观察[J].中国妇幼保健,2007,22:1906.
[37]李春洋,程静,黄朝霞,等.戊酸雌二醇与阿司匹林联合应用对诱发排卵周期子宫内膜发育及临床妊娠率的影响[J].温州医学院学报,2007,11;37(6):556-558.
[38]彭莲红,欧阳瑞霞,易清.阿司匹林对氯米芬诱导排卵患者子宫内膜容受性的影响[J].山东医药,2008,48(16):38.
[39]丁卫,刘嘉茵,钱云,等.低剂量阿司匹林在辅助生育技术中的应用[J].生殖医学杂志,2003,6;12(3):156-159.
[40]Hsieh YY, Tsai HD, Chang CC, et al. Low-dose aspirin for infertilewomen with thin endometrium receiving intrauterine insemination: aprospective, randomized study[J]. J Assist Reprod Genet.,2000,3;17(3):74-77.
[41]Dickey RP, Olar TT, Taylor SN, et al. Relationship of endometrialthickness and pattern to fecundity in ovulation induction cycles: effect ofclomiphene citrate alone and with human menopausal gonadotropin[J].Ferti Steril.,1993,4;59(4):756-760.
[42]郭玉琪,刘义,丁玉莲,等.小剂量阿司匹林在诱发排卵中对子宫内膜组织形态学的影响[J].生殖医学杂志,2008,8;11(4):203-205.
[43]Ruopp MD, Collins TC, Whitcomb BW, et al. Evidence of absence orabsence of evidence? A reanalysis of the effects of low-dose aspirin in invitro fertilization[J]. Fertil Steril.,2008,6;90(1):71-76.
[44]Dirckx K, Cabri P, Merien A, et al. Does low-dose aspirin improvepregnancy rate in IVF/ICSI? A randomized double-blind placebocontrolled trial[J]. Hum Reprod.,2009,4;24(4):856-860.
[45]Helms AK, Kittner SJ. Pregnancy and stroke[J]. CNS Spectr.,2005,7;10(7):580-587.
[46]Streck RD, Kumpf SW, Ozolins TR, et al. Rat embryos express transcriptsfor cyclooxygenase-1and carbonic anhydrase4,but not forcyclooxygenase-2,during organogenesis[J]. Birth Defects Res B DevReprod Toxicol.,2003,2;68(1):57-69.
[47]Hoozemans DA, Schats R, Lambalk CB, et al. Human embryoimplantation:current knowledge and clinical implantations in assistedreproductive technologies[J]. Reprod Biomed Online.,2004,12;9(6):692-715.
[48]Loeb L. Ueber die experimentelle Erzeugung von Knoten vonDeciduagewebe in dem Uterus des Meerschweinchens nachstattgefundener copulation[J]. Centrbl. allg. Path. path. Anat.,1907,18:563.
[49]罗国群,邓伟芬,马文敏.机械刺激子宫内膜对内膜形态不良者IVF-ET临床结局的影响[J].生殖与避孕,2012,2;32(2):139-142.
[50]Dekel N, Gnainsky Y, Granot I, et al. Inflammation and implantation[J].Am J Reprod Immunol.,2010,1;63(1):17-21.
[51]王瑶,冯云,牛志宏,等.子宫内膜轻创对着床相关因子及IVF妊娠结局影响的研究[J].生殖与避孕,2007,7;27(7):454-462.
[52]Lessey BA, Gui Y, Apparao KB, et al. Regulated expression ofheparin-binding EGF-like growth factor (HB-EGF) in the humanendometrium: a potential paracrine role during implantation[J]. MolReprod Dev.,2002,8;62(4):446-455.
[53]Karpovich N, Chobotova K, Carver J, et al. Expression and function ofinterleukin-11and its receptor alpha in the human endometrium[J]. MolHum Reprod.,2003,2;9(2):752-801.
[54]李权,谭晓珊,王丽,等.机械刺激对C型子宫内膜种植窗期组织形态学的影响[J].贵州医药,2007,8;31(8):678-681.
[55]李蓉,钟凯,卢丽华,等.胚胎移植周期机械刺激子宫内膜提高临床妊娠率[J].生殖医学杂志,2007,12;13(6):342-345.
[56]葛明晓,张金玉,李海霞,等.搔刮术对子宫内膜形态不良患者体外受精-胚胎移植临床结局的影响[J].中华妇产科临床杂志,2012,9;13(5):352-354.
[57]胡玥玥,黄晓卉,江胜芳,等.子宫内膜浅搔刮对胚胎移植周期结局的影响[J].中国优生与遗传杂志,2012,20(10):121-122.
[1]张玉珍主编.中医妇科学[M].北京:中国中医药出版社,2002:364.
[2]Amato G, Izzo A, Tucker A, et al. Insulin-like growth factor bindingprotein-3reduction in follicular fluid in spontaneous and stimulatedcycles[J]. Ferti1Steril.,1998,70(1):141-144.
[3]石红.卵巢旁分泌与自分泌[J].中国实用妇科与产科杂志,2001,17(4):241.
[4]龚非力主编.医学免疫学[M].第二版.北京:科学出版社,2004:61.
[5]Spangelo BL, Farrimond DD, Pompilius M, et al. Interleukin-1beta andthymic peptide regulation of pituitary and glial cell cytokine expression andcellular proliferation[J]. Ann N Y Acad Sic.,2000,917:597-607.
[6]龚守良,赵勇,刘淑春. IL-1对垂体促性腺细胞及甲状腺轴分泌功能的短期效应[J].白求恩医科大学学报,2005,3(1):7-8.
[7]Morita Y, Perez GI, Maravei DV, et al. Targeted expression of Bcl-2inmouse oocytes inhibits ovarian follicle atresia and prevents spontaneous andchemotherapy-induced oocyte apoptosis in vitro [J]. Mol Endocrinol.,1999,13(6):841-850.
[8]Petroff MG, Petroff BK, Pate JL. Expression of cytokine messenger ribonucleic acids in the bovine corpus luteum[J]. Endocrinology,1999,140:1018-1021.
[9]李庆雷,倪江.细胞因子对卵巢功能的调节作用[J].生理科学进展,2000,31(4):361.
[10]Grasso G, Asano A, Minagawa T, et al. Immunohistochemical localizationof interferon-gamma in normal human ovary[J]. Gynecol Endocrinol.,1994,8(3):161-168.
[11]王秀霞,易晓芳,何丽霞.卵泡液中肿瘤坏死因子-α和干扰素-γ水平对体外受精结局的影响[J].中国实用妇科与产科杂志,2009,25(11):859-860.
[12]王秀霞,王天任,易晓芳,等.卵泡液中TNF-CC和IFN-γ与卵丘颗粒细胞凋亡关系的探讨[J].生殖与避孕,2010,30(8):519-522.
[13]Braat DD, Schoemaker R, Schoemaker J. Life table analysis of fecundityin intravenously gonadotropin-releasing hormone-treated patients withnormogonadotropic and hypogonadotropic amenorrhea [J]. Fertil Steril.,1991,56(2):265-272.
[14]胡静.卵巢内调节因子在多囊卵巢综合征发病中的作用[J].国外医学计划生育分册,2003,22(4):229.
[15]王国云,姜虹,晁岚,等.人卵丘颗粒细胞凋亡与卵子发育潜能关系的研究[J].生殖与避孕,2006,26(2):91-94.
[16]李芳,郑月慧,肖秋香,等.肿瘤坏死因子–α与卵子生成[J].生殖与避孕,2007,27(7):479-483.
[17]Chen HL, Marcinkiewicz JL, Sancho-Tello M, et al. Tumor necrosisfactor-alpha gene expression in mouse oocytes and follicular cells [J]. BiolReprod.,1993,48(6):707-714.
[18]Lee KS, Joo BS, Na YJ, et al. Relationships between concentrations oftumor necrosis factor-alpha and nitric oxide in follicular fluid and oocytequality[J]. J Assist Reprod Genet.,2000,17:222-228.
[19]路帅.补肾法、疏肝法对排卵障碍模型大鼠卵巢细胞因子影响的比较研究[D].石家庄:河北医科大学,2010.
[20]张昌军,王华,周艳梅.白细胞介素6及肿瘤坏死因子对体外受精-胚胎移植结局的影响[J].郧阳医学院学报,2003,22(5):257-261.
[21]Chae HD, Hong SH, Hong SH, et al.Influence of tumor necrosisfactor-alpha on estradiol, progesterone, insulin-like growth factor-II,andinsulin-like growth factor binding protein-1,2, and3in cultured humanluteinized granulosa cells[J]. Eur J Obstet Gynecol Reprod Biol.,2007,131:176-181.
[22]Wuttke W, Pitzel L, Knoke I, et al. Immune-endocrine interactionsaffecting luteal function in pigs[J]. J Reprod Fertil Suppl.,1997,52:19-29.
[23]J S Richards, D L Russell, R L Robker, et al. Molecular mechanism ofovulation and luteinization[J]. Mol Cell Endocrinol.,1998,145:47-54.
[24]Tamura K, Tamura H, Kumasaka K, et al. Ovarian immune cells expressgranulocyte-macrophage colony-stimulating factor (GM-CSF) duringfollicular growth and luteinization in gonadotropin-primed immaturerodents[J]. Mol Cell Endocrinol.,1998,142:153-163.
[25]Cohen PE, Zhu L, Pollard JW. Absence of colony stimulating factor-1inosteopetrotic (csfmop/csfmop) mice disrupts estrous cycles andovulation[J]. Biol ReProd.,1997,56:110-118.
[26]Salnassi A, Zhang L. Expression Pattetns of GM-CSF in human ovarianfollicular fluid and serum[J]. Hum Reprod.,2001,16:203.
[27]王喜艳,徐邦生,高银峰,等. BMP-6对卵巢功能和生殖能力作用的研究进展[J].生殖与避孕,2009,11:621.
[28]Mery L, Lefevre A, Benchaib M, et al. Follicular growth in vitro:detection of growth differentiation factor9(GDF9) and bonemorphogenetic protein15(BMP15) during in vitro culture of ovinecortical slices[J]. Mol Reprod Dev.,2007,74(6):767-774.
[29]Liu L, Rajareddy S, Reddy P, et al. Infertility caused by retardation offollicular development in mice with oocyte-specific expression ofFoxo3a[J]. Development,2007,134(1):199-209.
[30]Nilsson EE, Skinner MK. Kit ligand and basic fibroblast growth factorinteractions in the induction of ovarian primordial to primary follicletransition[J]. Mol Cell Endocrinol.,2004,214(1-2):19-25.
[31]Dong J, Albertini DF, Nishimori K, et al.Growth differentiation factor-9isrequired during early ovarian folliculogenesis[J]. Nature,1996,383:485-486.
[32]Hreinsson JG, Scott JE, Rasmussen C, et al. Growth differentiationfactor-9promotes the growth, development，and survival of human ovarianfollicles in organ culture[J]. J Clin Endocrinol Metab.,2002,87:316-321.
[33]Galloway SM, Gregan SM, Wilson T, et al. Bmp15mutations and ovarianfunction[J]. Mol Cell Endocrino.,2002,191:15-18.
[34]Matzuk MM. Revelations of ovarian follicle biology from gene knockoutmice[J]. Mol Cell Endocrinol.,2000,163(1-2):61-62.
[35]苗竹林,王自能,郑佩娥,等.生长分化因子-9在大鼠卵巢中的表达[J].暨南大学学报(医学版),2005:195-198.
[36]李爽,夏阳,夏天.补肾调冲方对半乳糖致POF大鼠始基卵泡募集及卵泡闭锁相关因子GDF-9表达的影响[J].辽宁中医杂志,2011,38(11):2267-2270.
[37]曲中玉.生长分化因子-9与FOXL2在卵巢组织中的表达与调控研究[D].济南:山东大学,2006.
[38]Cocquet J, Pailhoux E, Jaubert F, et al. Evolution and expression ofFOXL2[J]. J Med Genet.,2002,39(12):916-921.
[39]Weenen C, Laven JS, Von Bergh AR, et al. Anti-Müllerian hormoneexpression pattern in the human ovary: potential implications for initialand cyclic follicle recruitment[J]. Mol Hum Reprod.,2004,10(2):77-83.
[40]Durlinger AL, Gruijters MJ, Kramer P, et al. Anti-Müllerian hormoneinhibits initiation of primordial follicle growth in the mouse ovary[J].Endocrinology,2002,143(3):1076-1084.
[41]李键,乔杰.抗苗勒氏管激素在卵泡形成中的作用[J].中国优生与遗传杂志,2007,15(10):1.
[42]Mather JP, Moore A, Li RH.Activins, inhibins，and follistatins: furtherthoughts on a growing family of regulators[J]. Proc Soc Exp Biol Med.,1997,215(3):209.
[43]夏天.补肾调冲方对大鼠卵巢颗粒细胞增殖与分泌及其相关基因表达的影响[D].天津:天津中医药大学,2005.
[44]Ling N, Ying SY, Ueno N, et al. Isolation and partial characterization of aMr32,000protein with inhibin activity from porcine follicular fluid[J].Proc Natl Acad Sci USA.,1985,82(21):7217-7221.
[45]Roy SK, Greenwald GS. Immunohistochemical localization of epidermalgrowth factor-like activity in the hamster ovary with a polyclonalantibody[J]. Endoerinology,1990,126:1309-1317.
[46]赵明,方芳. EGF对大鼠卵巢颗粒细胞增殖与分化影响的研究[J].生理学报,1993,45(3):207-214.
[47]Procházka R, Srsen V, Nagyová E, et al. Developmental regulation ofeffect of epidermal growth factor on porcine oocyte-cumulus cellcomplexes: nuclear maturation, expansion, and F-actin remodeling[J]. MolReprod Dev.,2000,56:63-73.
[48]Wu J, Zhang L, Liu P. A new source of human oocytes: preliminary reporton the identification and maturation of human preantral follicles fromfollicular aspirates[J]. Hum Reprod.,1998,13:2561-2563.
[49]Reeka N, Berg FD, Brucker C. Presence of transforming growth factoralpha and epidermal growth factor in human ovarian tissue and follicularfluid[J]. Hum Reprod.,1998,13(8):2199-2205.
[50]许程洁,王鑫泉,陈毅斐,等.卵巢颗粒细胞激素与成纤维细胞生长因子的信号交流[J].四川生理科学杂志,2011,33(3):123-124.
[51]于元松,谭景和.卵巢中的胰岛素样生长因子系统[J].生理科学进展,2002,33(2):31.
[52]Spicer LJ, Santiago CA, Davidson TR, et al. Follicular fluidconcentrations of free insulin-like growth factor (IGF)-I during folliculardevelopment in mares[J]. Domest Anim Endocrinol.,2005,29(4):573-581.
[53]陈丹清,石一复.胰岛素样生长因子-I及其结合蛋白-I对促超排卵周期卵泡发育的影响[J].中华妇产科杂志,2000,35:719-721.
[54]Nilsson EE, Kezele P, Skinner MK. Leukemia inhibitory factor (LIF)promotes the primordial to primary follicle transition in rat ovaries[J]. MolCell Endocrinol.,2002,188(1-2):65-73.
[55]洪俊君,王子玉,王锋.干细胞因子在卵泡发育过程中的作用[J].细胞生物学杂志,2006,28:667-670.
[56]Sette C, Dolci S, Geremia R, et al. The role of stem cell factor and ofalternative c-kit gene products in the establishment, maintenance andfunction of germ cells[J]. Int J Dev Biol.,2000,44(6):599-608.
[57]Wang J, Roy SK. Growth differentiation factor-9and stem cell factorpromote primordial follicle formation in the hamster: modulation byfollicle-stimulating hormone[J]. Biol Reprod.,2004,20(3):577-585.
[58]Klinger FG, De Felici M. In vitro development of growing oocytes fromfetal mouse oocytes: stage-specific regulation by stem cell factor andgranulosa cells[J]. Dev Biol.,2002,244(1):85-95.
[59]严杰,乔杰.干细胞因子及其受体在卵泡早期发育中的作用[J].生殖与避孕,2008,12(12):739-743.
[60]董艳敏.干细胞因子与生殖医学的关系[J].中国性科学,2008,17(4):18-22.
[61]王桂红.干细胞因子在女性生殖过程中作用的初步研究[D].西安:第四军医大学,2003.
[62]Anasti JN, Kalantaridou SN, Kimzey LM, et al. Human follicle fluidvascular endothelial growth factor concentrations are correlated withluteinization in spontaneously developing follicles[J]. Hum Reprod.,1998,13(5):1144-1147.
[63]邢福旗,梁卫华,陈士岭.血管内皮生长因子在人卵巢和子宫内膜上的表达[J].第一军医大学学报,2000,20(5):453-455.
[64]Hornung D, Lebovic DI, Shifren JL, et al. Vectorial secretion of vascularendothelial growth factor by polarized human endometrial epithelialcells[J]. Fertil Steril.,1998,69(5):909-915.
[65]Sugino N, Kashida S, Takiguehi S, et al. Expression of vascularendothelial growth factor and its receptors in the human corpus luteumduring the menstrual cycle and in early pregnancy[J]. Clin EndoerinolMetab.,2000,85(10):3919-3924.
[2]乐杰主编.妇产科学[M].北京:人民卫生出版社,2008:351.
[3]丰有吉,沈铿主编.妇产科学[M].北京:人民卫生出版社,2010:394.
[4]刘伟,王丽岩.不明原因不孕患者小卵泡排卵的诊治意义[J].中华妇幼临床医学杂志(电子版),2007,4(3):94-95.
[5]赵得雄.小卵泡排卵不孕及习惯性流产患者的临床诊治研究[J].中国妇幼保健,2010,25:217-218.
[6]赵秀萍.小卵泡排卵中医证候学调查及分析[D].北京:北京中医药大学,2011.
[7]丰有吉,沈铿主编.妇产科学[M].北京:人民卫生出版社,2010:24.
[8]韩玉芬,程淑蕊,敬文娜,等.卵巢储备功能下降的预测及治疗[J].中国计划生育学杂志,2007,2:117.
[9]李焱,陈闯.雌孕激素序贯治疗卵巢功能低下的临床观察[J].中国医药指南,2012,2(10):113-114.
[10]连方,陈艳花.中西医结合改善卵巢储备的研究[C].全国中西医结合围绝经期专题学术会议论文集,2010:36-37.
[11]王素荣,李辉杰.人工周期治疗60例卵巢储备功能低下的体会[J].现代医药卫生,2011,27(4):566-567.
[12]Tarlatzis BC, Zeoiridis L, Grimbizis G, et al. Clinical management ofovarian response to stimulation for IVF: a systematic review[J]. HumReprod Update.,2003,9(1):61-76.
[13]Ubaldi FM, Rienzi L, Ferrero S, et al. Management of poor responders inIVF[J]. Reprod Biomed Online.,2005,10(3):235-246.
[14]Ana Claver o, Jose A Castillab, Ana I Nunez. Apoptosis in humangranulose cells after induction of ovulation in women participating in anintracytoplasmic sperm injection program[J]. Obstetrics&Gynecologyand Reproductive Biology,2003,110:181-185.
[15]王增艳,何方方.空卵泡综合征研究进展[J].生殖医学杂志,2006,15(5):357-360.
[16]Reichman DE, Hornstein MD, Jackson KV, et al. Empty folliclesyndrome-does repeat administration of hCG really work?[J]. Fertil Steril.,2010,94(1):375-377.
[17]龙兴宇.控制性超排卵中过早黄素化对体外受精影响妊娠结局及分子机制的初步研究[D].长沙:中南大学,2009.
[18]Thomas K, Thomson AJ, Wood SJ, et al. Endometrial integrin expressionin women undergoing IVF and ICSI: a comparison of the two groups andfertile[J]. Hum Reprod.,2003,18(2):364-369.
[19]Mirkin S, Nikas G, Hsim JG, et al. Gene expression profiles and endstructural/functional features of the pri-implantation endometrium innature and gonadotropin-simulated cycles[J]. Clin Endocrinol Metab.,2004,89(11):5742-5752.
[20]Massai MR, Ziegler D, Bergeron C, et al. Clomiphene citrate affectscervical mucus and endometrial morphology independently of the changesin Plasma hormonal levels induced by multiple follicular recruitment[J].Fertil Steril.,1993,59(6):1179.
[21]章辉.排卵障碍性不孕症中医临床症候分布规律的研究[D].广州:广州中医药大学,2008.
[22]周剑平.中药加克罗米芬治疗排卵功能障碍性不孕的临床观察[J].浙江中医药大学学报,2006,30(3):255-256.
[23]曹泽毅主编.中华妇产科学[M].北京:人民卫生出版社,1999:2200-2201.
[24]罗元恺.罗元恺论医集[M].北京:人民卫生出版社,1990:7.
[25]史广宇,单书剑主编.不孕专辑[M].北京:中医古籍出版社,1992:1-10.
[26]徐升阳,王克林,贺漪,等主编.徐升阳妇科医著选编[M].北京:中医古籍出版社,2005:104-108.
[27]李宝顺主编.名医名录[M].北京:中医古籍出版社,1993,3:396-401.
[28]徐琳,曾春晖.徐升阳辨证治疗不孕症复杂案例4则[J].世界中医药杂志,2011,6(1):57-59.
[29]徐琳,徐升阳. IVF-ET助孕失败后服中药再次移植20例结局分析[J].中西医结合研究,2012,4(2):17-18.
[30]王静,李红梅,徐琳.徐升阳主任医师治疗不孕症经验[J].新中医,2012,44(9):146-147.
[31]刘雯雯.徐升阳教授经验方补肾助孕丸对肾虚型不孕患者助排卵的临床观查[J].中国营养保健,2012,5(5):149.
[1]张玉珍主编.中医妇科学[M].北京:中国中医药出版社,2002:364.
[2]丰有吉,沈铿主编.妇产科学[M].北京:人民卫生出版社,2010:21.
[3]陈静,阮详燕.65例育龄妇女卵巢储备功能下降的临床研究分[J].医学综述,2011,4(17):1253.
[4]Sun W, Stegmann BJ, Henne M, et al. A new approach to ovarian reservetesting[J]. Fertil Steril.,2008,90(6):2196-2202.
[5]Maheshwari A, Fowler P, Bhattacharya S. Assessment of ovarian reserveshould we perform tests of ovarian reserve routinely?[J]. Hum Reprod.,2006,21(11):2729-2735.
[6]Templeton A, Morris JK, Parslow W. Factors that affect outcome of in-vitrofertilisation treatment[J]. Lancet.,1996,348(9039):1402-1406.
[7]马灵芝,李爽,夏天.卵巢储备力降低的监测[J].现代中西医结合杂志,2010,19(11):1425-1427.
[8]曹泽毅主编.中华妇产科学[M].北京:人民卫生出版社,1999:2138-2139.
[9]张吟,许小凤,毛菲.卵巢储备功能下降的病因病机初探[J].黑龙江中医药,2009,4:3.
[10]许小凤,谈勇,陈宣伊.卵巢储备功能下降中医辨证思路和优势[J].中国中医药信息杂志,2009,16(12):88-89.
[11]许小凤,谈勇,薛晓明,等.血清抑制素B水平预测卵巢储备功能的临床价值[J].现代妇产科进展,2008,17(8):568-570．
[12]de Taraciuk MB, Nolting M, Fernandez G, et al. Psychological assessmentof patients with premature ovarian failure[J]. Gynecol Endoerinol.,2008,24(1):45-53.
[13]陈和利,金石,王力,等.知识女性月经失调与精神因素关系调查[J].江西中医学院学报,2007,19(3):86-88.
[14]马丽灵,阮祥燕.100例卵巢早衰相关因素的调查分析[J].实用妇产科杂志,2009,25(4):212-215.
[15]Matikainen T, Perez Gl, Jurisicova A, et al. Aromatic hydrocarbonreceptor-driven Bax gene expression is required for premature ovarianfailure biohazardous environmental chemicals[J]. Nat Genet.,2001,28(4):355-360.
[16]尹薇薇.卵巢储备功能下降女性的生存质量及中医体质类型的研究[D].广州:广州中医药大学,2011.
[17]Ennis S, Ward D, Murray A. Nonlinear association between CGG repeatnumber and age of menopause in FMR1premutation carriers [J]. Eur JHum Genet.,2006,14(2):253-255.
[18]Rao L, Babu A, Padmalatha V, et al. Novel X-chromosomal defectassociated with abnormal ovarian function[J]. J Obstet Gynaecol Res.,2005,31(l):12-15.
[19]Kok H S, van Asselt K M, van der Schouw Y T, et al. Genetic studies toidentify genes underlying menopausal age[J]. Human reproduction update,2005,11(5):483-493.
[20]Steiner AZ, Baird DD, Kesner JS. Mother's menopausal age is associatedwith her daughter's early follicular phase urinary follicle-stimulatinghormone level[J]. Menopause,2008,15(5):940-944.
[21]Kamada M, Daitoh T, Mori K, et al. Etiological implication ofautoantibodies to zona pellucida in human female infertility[J]. Am JReprod Immunol.,1992,28:104.
[22]马张,孔北华,邓晓惠.抗卵巢抗体对体外受精-胚胎移植过程及结局的影响[J].现代妇产科进展,2004,13(6):453.
[23]Bagavant H, Adams S, Terranova P, et al. Autoimmune ovarianinflammation triggered by proinflammatory (Th1) T cells is compatiblewith normal ovarian function in mice[J]. Biol Reprod.,1999,61(3):635-642.
[24]Chen S, Sawicka J, Betterle C, et al. Autoantibodies to steroidogenicenzymes in autoimmune polyglandular syndrome, Addison's disease, andpremature ovarian failure[J]. J Clin Endocrinol Metab.,1996,81(3):1871-1876.
[25]Russel P. The clinicopathological features of primary ovarian failure [J].Verh Dtsch Ges Pathol.,1997,81:197-209.
[26]Ghersevich S, Isomaa V, Vihko P. Cytokine regulation of the expression ofestrogenic biosynthetic enzymes in cultured rat granulosa cells[J]. MolCell Endocrinol.,2001,172(1-2):21-30.
[27]王一峰,欧汝强,杨宁,等.卵巢早衰患者血清抗透明带抗体和肿瘤坏死因子-α, γ-干扰素及白细胞介素-2的分析[J].生殖医学,2002,11(1):7-10.
[28]蒋利华,姚珍薇,张新华,等.卵巢早衰危险因素的病例对照研究[J].重庆医科大学学报,2006,31(3):424-425.
[29]Barbarino-Monnier P, Gobert B, Guillet-Rosso F, et a1. Antiovaryantibodies, repeated attempts,and outcome of in vitro fertilization [J].Fertil and Steril.,1991,56:289.
[30]黄邱朝,王国洪,赵技文,等.不孕症妇女抗卵巢抗体与血清激素水平的关系[J].上海医学,1997,20(6):573.
[31]Tuohy VK, Altuntas CZ. Autoimmunity and premature ovarian failure[J].Curr Opin Obstet Gynecol.,2007,19(4):366.
[32]Laissue P, Lakhal B, Benayoun BA, et al. Functional evidence implicatingFOXL2in non-syndromic premature ovarian failure and in the regulationof the transcription factor OSR2[J]. Med Genet.,2009,46(7):455-457.
[33]Hviid A, Rubin S, Mühlemann K. Mumps[J]. Lancet.,2008,37(l):932-944.
[34]薛艳军,罗新.卵巢子宫内膜异位囊肿剔除术中的机械损伤和热损伤对卵巢储备的影响[J].广东医学,2008,29(5):720-721.
[35]刘萍,孙丽,全松.腹腔镜卵巢囊肿剥除术对卵巢储备功能及体外受精-胚胎移植的影响[J].广东医学,2009,30(6):950-952.
[36]于传鑫.实用妇科内分泌学[M].第二版.上海:复旦大学出版社,2004:100.
[37]丰有吉主编.妇产科学[M].北京:人民卫生出版社,2002:345.
[38]丁曼琳.妇产科疾病诊断与鉴别诊断[M].第二版.北京:人民卫生出版社,1999:357.
[39]赵明霞,王丽红,孙银婷,等.血清抑制素B,窦卵泡数预测高龄不育妇女卵巢储备功能的临床研究[J].中国医学文摘(计划生育妇产科学),2008,27(6):411-413.
[40]Klinkert ER, Broekmans FJ, Looman CW, et al. Expected poor responderson the basis of an antral follicle count do not benefit from a higher startingdose of gonadotrophins in IVF treatment:a randomized controlled trial[J].Hum Reprod.,2005,20(3):611-615.
[41]饶玉梅.不孕不育妇女卵巢储备功能的检测[J].中国优生与遗传杂志,2003,11(2):143.
[42]Zaidi J, Barber J, Kyei-Mensah A, et al.Relationship of ovarian stromalblood flow at the baseline ultrasound scan to subsequent follicularresponse in an in vitro fertilization program[J]. Obstet Gynecol.,1996,88:779.
[43]Kupesic S, Kurjak A, Bjelos D, et al. Three-dimensionalultrasonographic ovarian measurements and in vitro fertilization outcomeare related to age[J]. Fertile Steril.,2003,79(1):190-197.
[44]Sharara FI, MaClamrock HD. The effect of aging on ovarian volumemeasurements in infertile women[J]. Obstet Gynecol.,1999,94(11):57-60.
[45]Tepper R, Zalel Y, Markov S, et al. Ovarian volume in postmenopausalwomen--suggestions to an ovarian size nomogram for menopausal age[J].Aeta Obstet Gyneeol Scand.,1995,74:208-211.
[46]Smotrich DB, Widra EA, Gindoff PR, et al. Prognostic value of day3estradiol on in vitro fertilization outcome[J]. Fertil Steril.,1995,64:1136-1140.
[47]Hall JE, Welt CK, Cramer DW. Inhibin A and inhibin B reflect ovarianfunction in assisted reproduction but are less useful at predictingoutcome[J]. Hum Reprod.,1999,14:409-415.
[48]吴日然,廖月蝉,叶云,等.测定血清抑制素B水平预测卵巢储备力及调节控制性超排卵用药的研究[J].中华妇产科杂志,2005,40(10):679-681.
[49]陈士岭.卵巢储备功能的评价[J].国际生殖健康/计划生育杂志,2009,28(9):283.
[50]Gürbüz B, Yalti S, Ficicioglu C, et a1. The relation of serum and follicularfluid leptin and ovarian steroid levels in response to induction of ovulationin in vitro fertilization cycles[J]. European Journal of Obstetrics&Gynecology and Reproductive Biology,2005,118:214-218.
[51]雷纯钢,刘小敏.卵巢储备功能的评价[J].右江民族医学院学报,2008,1:139-141.
[52]邓远征,李凤玲.补肾疏肝活血法治疗卵巢储备功能下降的临床观察[J].内蒙古中医药,2012,1:31.
[53]李焱,陈闯.雌孕激素序贯治疗卵巢功能低下的临床观察[J].中国医药指南,2012,10(2):113-114.
[54]Gleicher N1, Weghofer A, Barad DH. Improvement in diminished ovarianreserve after dehydroepiandrosterone supplementation[J]. ReproductiveBioMedicine Online,2010,21:360-365．
[55]Barad D, Gleicher N. Effect of dehydroepiandrosterone on oocyte andembryo yields, embryo grade and cell number in IVF[J]. HumanReproduction,2006,21(11):2845-2849．
[56]陈新娜. DHEA和卵巢功能低下1例及文献复习[J].现代妇产科进展,2010(9):715-715.
[57]徐千花,曹云霞,魏兆莲.促性腺激素释放激素抑制剂在卵巢功能低下患者促排卵中的应用[J].中国妇幼保健,2008,23:3883-3885.
[58]Tesarik J, Hazout A, Mendoza C. Improvement of delivery and live birthrates after ICSI in women aged>40years by ovarian co-stimulation withgrowth hormone[J]. Human Reproduction,2005,20(9):2536-2541.
[59]丁国莲,黄荷凤.生长激素在辅助生殖技术中的应用及作用机制[J].国际生殖健康/计划生育杂志,2008,6:007.
[60]宋慧玲.生长激素对卵巢储备功能低下患者IVF-ET治疗结局的影响[D].郑州:郑州大学,2011.
[1]许小凤,谈勇,陈宣伊.卵巢储备功能下降中医证治思路和优势[J].中国中医药信息杂志,2009,16(12):88-89.
[2]李淑萍.滋肾疏肝法治疗卵巢储备功能下降35例疗效观察[J].四川中医,2004,12(2):62-63.
[3]杨胜华.滋肾育胎丸对卵巢储备功能下降患者卵巢功能的影响[D].广州:广州中医药大学,2012.
[4]苍荣,夏天,王宝娟.韩冰运用补肾调冲方治卵巢储备功能下降性不孕症经验[J].江西中医药,2012,1(1):15-16.
[5]王琳.补肾益天癸提高高龄不孕妇女卵巢反应性的临床研究[D].济南:山东中医药大学,2002.
[6]徐眠,司徒仪,李丽芸,等.中医补肾法对高龄不孕妇女的卵巢储备功能的调控[J].广州中医药大学学报,2004,21(7):267-270.
[7]阮怀玲.中药周期疗法对卵巢储备功能降低者的临床疗效观察[D].广州:广州中医药大学,2011.
[8]陈益昀.艾灸结合中药治疗卵巢功能早衰临床观察[J].山西中医,2010,26(5):29-30.
[9]张迎春,李芳园,李兰荣,等.针药对卵巢储备功能影响的临床研究[J].四川中医,2010,28(2):103-104.
[10]潘芳,俞瑾.中西医结合治疗卵巢功能低下性不孕症48例临床观察[C].全国第八次中医妇科学术研讨会论文汇编,2008:112-114.
[11]连方,张建伟,张宁,等.中西医结合疗法在试管婴儿技术中的应用[J].山东中医药大学学报,2002,26(3):182-183.
[1]邹移海,徐志伟,苏钢强.实验动物学[M].北京:科学出版社,2004:84.
[2]曹俊岩.雷公藤多苷致大鼠卵泡发育障碍模型的中医证候属性研究[D].成都:成都中医药大学,2011.
[3]付丽.雷公藤多苷致大鼠卵巢功能低下模型的病理机制与中医证候属性研究[D].成都:成都中医药大学,2010.
[4]谌婕,吴克明,王家葵,等.雷公藤多甙致雌性小鼠肾虚生殖功能低下动物模型的研究[J].中药新药与临床药理,2007,18(3):208-211.
[5]张黎鹏.雷公藤多甙致雌性小鼠肾虚生殖功能低下模型的复制及机理探讨[D].成都:成都中医药大学,2007.
[6]张黎鹏.雷公藤多甙致雌性小鼠生殖功能低下模型证候初探[J].福建中医药,2007,4(2):43.
[7]曹俊岩,范宏元,曾莉,等.从细胞因子研究雷公藤多苷致大鼠卵巢功能低下模型的中医证候属性[J].辽宁中医杂志,2012,39(11):2282-2283.
[8]倪张俊.雷公藤致大鼠药源性卵巢功能耗损模型建构与补肾法干预研究[D].广州:广州中医药大学,2013.
[9]高慧,杨涓,韩冰,等.药物性卵巢早衰动物模型的研究[J].国医论坛,2007,22(3):22-25.
[10]钱绍帧.雷公藤的药理及抗生育作用[J].江苏医药,1987,13(12):646-649.
[11]乔子红.雷公藤抗生育作用的临床及实验研究概况[J].中级医刊,1990,25(2):70-72.
[12]高玉平,陈德甫,朱建善,等.雷公藤多苷对子宫肌瘤组织及肌组织ER和PR表达的影响[J].上海第二医科大学学报,2003,23(1):50.
[13]谷春霞,陶学廉,葛秦生,等.雷公藤多苷致闭经原因探讨[J].中国医学科学院学报,1989,11(2):151.
[14]王世间.卵巢疾病[M].北京:人民卫生出版社,2004:102-114.
[1]郑家润,刘季和,徐兰芳,等.雷公藤总甙的毒性研究[J].中国医学科学院学报,1983,5(2):73-78.
[2]赵柳霞.雷公藤多甙治疗子宫肌瘤64例[J].中国中西医结合杂志,2003,23(10):787-788.
[4]徐叔云,卞如濂,陈修.药理实验方法学[M].北京:人民卫生出版社,2006:202-204.
[5]王瑞峰,郝丽,潘美华,等.雌孕激素替代治疗雷公藤多甙致雌性大鼠生殖系统损害的实验研究[J].中国医科大学学报,2008,4:198.
[6]姜娇娇.雷公藤多甙及雌孕激素治疗对大鼠卵巢Bcl-2和Bax表达的实验研究[D].合肥:安徽医科大学,2010.
[7]陈奇.中药药理实验方法[M].北京:人民卫生出版社,1994:206.
[8]张建民主编.卵巢病理学[M].南昌:江西科学技术出版社,2006:6-18.
[9]陈乐真主编.妇产科诊断病理学[M].北京:人民军医出版社,2002:261-263.
[10]林科雄,王长征,钱桂生.雷公藤甲素对诱导CD4+、 CD8+T细胞凋亡的作用[J].免疫学杂志,2000,6(l):24-26.
[11]Tilly JL, Kowalski KI, Johnson AL, et al. Involvement of apoptosis inovarian follicular atresia and postovulatory regression[J]. Endocrinology,1991,129(5):2799-2801.
[12]Fanchin R, Schon uer LM, Righini C, et al. Serum anti-Müllerianhormone dynamics during controlled ovarian hyperstimulation[J]. HumReprod.,2003,18(2):328.
[13]庄广伦,李轶,梁晓燕.诱导排卵适应证与方案的应用专题讨论[J].实用妇产科杂志,2007,23(3):131.
[14]徐珉,司徒仪,李丽芸,等.中医补肾法对高龄不孕妇女的卵巢储备功能的调控[J].广州中医药大学学报,2004,21(4):267-271.
[15]李军,王翠霞,陈莹,等.补肾复方延缓雌性大鼠卵巢早衰的实验研究[J].辽宁中医杂志,2007,34(5):681-683.
[16]张树成,沈明秀,蔡连香,等.补肾调经和养血补肾方药调经促排卵作用的实验研究[J].中医杂志,1999,40(6):369.
[17]高慧,杨涓,夏天,等.补肾调冲方对卵巢早衰人鼠性激素水平和卵巢组织形态学的影响[J].国医论坛,2008,23(1):35-39.
[18]陆华,刘敏如,李养梅.养精汤促卵泡发育的临床观察[J].中国中西医结合杂志,1998,18(4):217.
[19]谈勇,石川睦男.补肾调周法在体外受精-胚移植期前应用的临床观察[J].中国中医药信息杂志,2001,12(12):45-46.
[20]李仪奎.中药药理实验方法学[M].上海:上海科学技术出版社,1991:224.
[21]Aisen PS, Berg JD, Craft S, et al. Steroid-induced elevation of glucose in Alzheimer's disease: relationship to gender,apolipoprotein E genotype and cognition[J]. Psychoneuroendocrinology,2003,1:113-120.
[22]单志群,葛蕾.补肾调冲药诱发排卵的实验研究[J].深圳中西医结合杂志,1998,8(1):11-13.
[23]李伊然.雌激素及其受体与卵母细胞成熟的相关性[D].西宁:宁夏医科大学,2013.
[24]岳占碰,张学明,马琳.雌激素对哺乳动物卵泡发育影响的研究进展[J].中国畜牧杂志,2007,43(1):41-43.
[25]Homburg R. Clomiphene citrate-end of an era? A mini-review[J]. HumReprod.,2005,20:2043-2051.
[26]郭玉琪,张展,刘义,等.克罗米芬对子宫内膜发育的影响[J].生殖医学杂志,2006,15(4):129.
[27]Unfer V, Costabile L, Gerli S,e t al. Low does of ethinyl estradiol canreverse the antiestrogenic effets of clomiphene citrate on endometrium[J].Gynecol Obstet Invest.,2001,51(2):120-123.
[28]石红.卵巢旁分泌与自分泌[J].中国实用妇科与产科杂志,2001,17(4):241-243.
[29]许爱霞,汪雁,徐良全,等.卵泡发育中相关基因的调控[J].生殖与避孕,2008,28(12):745-750.
[30]严杰,乔杰.干细胞因子及其受体在卵泡早期发育中的作用[J].生殖与避孕,2008,12(12):739-743.
[31]洪俊君,王子玉,王锋,等.干细胞因子在卵泡发育过程中的作用[J].细胞生物学杂志,2008,28:667-670.
[32]赵海波,何亚绒,李爱莉,等.卵泡液干细胞因子水平对卵母细胞发育、受精和卵裂影响的实验研究[J].中国计划生育学杂志,2006,130(8):475-476.
[33]Jin X, Han CS, Zhang XS, et al. Signal transduction of stem cell factor inpromoting early follicle development[J]. Mol Cell Endocrinol.,2005,229(1-2):3-10.
[34]王桂红,赵海波,辛晓燕.人卵泡液中干细胞因子水平及其对卵泡发育的影响[J].第四军医大学学报,2003,24(6):543-545.
[35]常秀峰.补肾调经方对IVF-ET妊娠结局及颗粒细胞凋亡和OSFs的影响[D].石家庄:河北医科大学,2011.
[36]于晓娜.骨形态发生蛋白15基因与人类卵母细胞及卵泡发育[J].国际生殖健康/计划生育杂志,2008,27(7):215-217.
[37]Thomas FH, Vanderhyden BC. Oocyte-granulosa cell interactions duringmouse follicular development: regulation of kit ligand expression and itsrole in oocyte growth[J]. Reprod Biol Endocrinol.,2006,4:19.
[38]李爽,夏阳,夏天.补肾调冲方对半乳糖致POF大鼠始基卵泡募集及卵泡闭锁相关因子GDF-9表达的影响[J].辽宁中医杂志,2011,38(11):2267-2270.
[39]苗竹林,王自能,郑佩娥,等.生长分化因子-9在大鼠卵巢中的表达[J].暨南大学学报(医学版),2005:195-198.
[40]Chauhan P, Sodhi A, Tarang S. Cisplatin-treated murine peritonealmacrophages induce apoptosis in L929cells: role of Fas-Fas ligand andtumor necrosis factor-tumor necrosis factor receptor1[J]. Anticancer Drug,2007,18(2):187-196.
[41]李键.生长分化因子9在卵泡发育中的调控作用[J].国际生殖健康/计划生育杂志,2008,27(2):84.
[42]张树成,沈明秀,蔡连香,等.补肾调经和养血补肾方药调经促排卵作用的实验研究[J].中医杂志,1999,40(6):369.
[43]杨桂云,王佩娟,贾晓斌,等.“补肾活血汤”对小鼠早期胚胎发育的作用[J].江苏中医,2000,21(11):40.
[44]Shetty G, Krishnamurthy H, Krishnamurthy HN, et al. Effect of estrogendeprivation on the reproductive physiology of male and female primates[J].J Steroid Biochem Mol Biol.,1997,61(3-6):157-166.
[45]郭鹊晖,郑志群.来曲唑的促排卵及胚胎毒性的研究进展[J].生殖与避孕,2009,29(2):120-124.
[46]耿蔷,郭遂群,全松,等.来曲唑用于促排卵对卵泡发育和子宫内膜影响的临床观察[J].实用医学杂志,2010,26(12):2209-2211.
[1]Exley GE, Tang C, McElhinny AS, et a1. Expression of caspase and BCL-2apoptotic family members in mouse preimplantation embryos[J]. BiolReprod.,1999,61(1):231-239.
[2]Jurisicova A, Antenos M, Varmuza S, et al. Expression of apoptosis-relatedgenes during human preimplantation embryo development: potential rolesfor the Harakiri gene product and Caspase-3in blastomere fragmentation[J].Mol Hum Reprod.,2003,9(3):133-141.
[3]Reed JC. Bcl-2and the regulation of programmed cell death[J]. J Cell Biol.,1994,124(1-2): l-6.
[4]Kugu K, Ratts VS, Piquette GN, et al. Analysis of apoptosis and expressionof bcl-2gene family members in the human and baboon ovary[J]. CellDeath Differ.,1998,5:67-76.
[5]刘岚,王元佩,施作霖,等.黄体功能不全患者月经子宫内膜中雌孕激素受体、细胞凋亡及bcl-2、bax蛋白的表达[J].中华妇产科杂志,2002,37(1):47-48.
[6]吴际,张丽珠,李潭,等.性激素对人卵巢颗粒细胞凋亡的作用[J].中华妇产科杂志,1998,33(3):157-159.
[7]蔡泽骏.性激素对大鼠卵巢颗粒细胞凋亡基因表达的作用[J].海峡药学,2002,14(6):22-23.
[8]秦佳佳,李瑞满.坤宁安对为绝经期大鼠卵巢颗粒细胞凋亡相关因子Bax及Bax mRNA的影响[J].湖南中医学院学报,2006,26(3):23-24.
[9]许小凤,谈勇,江国荣,等.补肾填精中药干预雷公藤多甙致卵巢储备下降大鼠卵巢功能的实验研究[J].中国中医基础医学杂志,2011,11(7):1225-1227.
[10]苗小芬,许小凤,陈宣伊,等.补肾活血组方对大鼠卵巢颗粒细胞的作用[J].苏州大学学报(医学版),2010,30(4):741-747.
[11]许小凤,谈勇,陈宣伊,等.补肾活血中药对雷公藤致卵巢储备下降大鼠颗粒细胞凋亡的影响[J].医学研究杂志,2009,38(12):123-125.
[12]孙海芸,陈云芝,薛晓鸥,等.四物合剂对化疗后大鼠卵巢形态及颗粒细胞凋亡的影响[J].中国实验方剂学杂志,2012,18(5):257-259.
[1]Lin HY, Harris TL, Flannery MS, et al. Expression cloing of an adenylatecyclase-coupled calcitonin receptor[J]. Science,1991,254:1022.
[2]Means AR, VanBerkum MF, Bagehi I, et al. Regulatory function ofcalmodulin[J]. Pharmacol Ther.,1991,50:225-270.
[3]Ding YQ, Zhu LJ, Bagchi MK, et al. Progesterone stimulates calcitoningene expression in the uterus during implantation [J]. Endoerinology,1994,135:2265.
[4]Koji Yoshinaga. Endocrinology of Embryo-Endometrium Interactions[M].New York: Plenum Press,1994:391-392.
[5]张艳萍,武玉玲,邴鲁军,等.降钙素受体在小鼠早期胚胎及围植入期子宫内膜的表达[J].山东大学学报,2005,12:1105-1106.
[6]冉雪梦,张华,邰国香,等.毓麟珠加减方对促排卵后子宫内膜CTmRNA表达的影响[J].中医研究,2007,2:29-31
[7]付志红,陈士岭,邢福祺.降钙素对人类胚胎着床的影响[J].中华妇产科杂志,2002,37(1):184.
[8]Carson DD, Bagchi I, Dey SK, et al. Embryo implantation[J]. Dev Biol.,2000,223(2):217-237.
[9]王伟,刘栋,王秀萍.降钙素对胚胎着床的影响机理[J].生物技术通报,2007,2:44-46.
[10]谢晓鹰,杨纫姝,毛伟平.钙调素拮抗剂与细胞内Ca2+浓度对人蜕膜细胞活力的影响[J].动物学报,1999,45(1):80-87.
[11]Zhu LJ, Cullinan-Bove K, Polihronis M, et al. Calcitonin is aprogesterone-regulated marker that forecasts the receptive state ofendometrium during implantation[J]. Endocrinology,1998,139(9):3923-3934.
[12]陆楠,高英茂,李少玲.大鼠胚泡植入过程中子宫内膜降钙素的动态表达及其与血清雌、孕激素水平的关系[J].生殖医学杂志,2004,6(3):158-162.
[13]郭艺红.白血病抑制因子、胞饮突与子宫内膜容受性关系的实验研究[D].郑州:郑州大学,2006.
[14]孙振高.补肾中药对超排卵周期子宫内膜容受性及整合素β3/骨桥蛋白时序表达的影响[D].济南:山东中医药大学,2009.
[15]陈海燕.黄体功能不全的病因、诊断和治疗[J].医学综述,1999,5(6):256-259.
[16]汪宏波,占海英,李红发.黄体功能不全患者着床期子宫内膜雌孕激素受体的表达及超微结构改变[J].中国妇幼保健,2009,12:44-49.
[17]张华,冉雪梦,陈芊,等.补肾活血方增强子宫内膜降钙素基因表达的临床研究[J].中国计划生育学杂志,2007,2:171-173.
[18]曹蕾,罗颂平,欧汝强.补肾健脾中药复方对肾虚模型大鼠子宫内膜容受性的影响[J].中华中医药杂志,2011,26(5):1057-1061.
[19]邓伟民,赵彦鹏,葛明晓,等.益气血补肝肾中药对体外受精-胚胎移植临床结局的影响[J].辽宁中医药大学学报,2011,13(6):5-7.
[20]曹蕾,罗颂平,欧汝强,等.补肾健脾法对复发性流产患者子宫内膜容受性的干预作用[J].广州中医药大学学报,2010,27(11):562-565.
[1]徐升阳,王克林,贺漪,等主编.徐升阳妇科医著选编[M].北京:中医古籍出版社,2005:104-108.
[2]罗元恺.罗元恺论医集[M].北京:人民卫生出版社,1990:7.
[3]史广宇,单书剑主编.不孕专辑[M].北京:中医古籍出版社,1992:1-10.
[4]许金晶,吴育宁.阴虚体质与卵巢储备功能下降[J].中华中医药杂志,2012,27(6):1621-1623.
[5]张荣,邓伟民.卵巢低反应患者中医症候分布研究[J].辽宁中医药大学学报,2013,15(11):98-100.
[6]王静,李红梅,徐琳.徐升阳主任医师治疗不孕症经验[J].新中医,2012,9:146-147.
[7]刘雯雯.徐升阳教授经验方补肾助孕丸对肾虚型不孕患者助排卵的临床观查[J].中国营养保健,2012,5(5):149.
[8]徐琳,曾春晖.徐升阳辨证治疗不孕症复杂案例4则[J].世界中医药杂志,2011,6(1):57-59.
[1]叶海涌.淫羊藿苷及其拟代谢产物的雌激素样作用体外研究[D].杭州:浙江大学,2004.
[2]赵丕文,牛建昭,王继峰,等.6种中药活性成分植物雌激素作用的比较研究[J].中国药学杂志,2007,42(12):1852-1855.
[3]陈颐.补肾活血方改善GnRHa诱发低雌激素状态的疗效观察[D].广州:广州中医药大学,2011.
[4]巴文君,孙丽萍,张秋菊,等.补骨脂对初老小鼠体内雌孕激素水平作用实验研究[J].中医药学报,2010,5:19-21.
[5]郝庆秀,王继峰,牛建昭,等.熟地等4味中药的植物雌激素作用的实验研究[J].中国中药杂志,2009,3(5):620-623.
[6]牛建昭.十种中药植物雌激素样作用及其机制的研究[D].北京:北京中医药大学,2009.
[7]Fan GW, Gao XM, Wang H, et al. The anti-inflammatory activities ofTanshinone IIA, an active component of TCM, are mediated by estrogenreceptor activation and inhibition of iNOS[J]. J Steroid Biochem Mol Biol.,2009,113(3/5):275-280.
[8]陶仕英.二仙汤及活性成分植物雌激素样作用机制研究[D].北京:北京中医药大学,2011.
[9]赵洁,侯连兵.植物雌激素的活性成分及其生物活性研究进展[J].中药材,2005,5(5):524-526.
[10]康建颖.植物雌激素的研究进展以及在妇科领域的应用概况[D].成都:成都中医药大学,2006.
[11]Younis JS, Skournik A, Radin O, et al. Poor oocyte retrieval is amanifestation of low ovarian reserve[J]. Fertil Steril.,2005,83(2):504-507.
[12]Duru NK, Cincik M, Dede M, et al. Retrieval of zona-free immatureoocytes in a woman with recurrent empty follicle syndrome: a casereport[J]. J Reprod Med.,2007,52(9):858-863.
[13]李承慈.植物雌激素的探讨[J].国外医学计划生育分册,2000,19(5):87-90.
[14]李培旭,李尚为,彭芝兰,等.超排卵对小鼠卵母细胞和胚胎发育潜能的影响[J].四川大学学报(医学版),2007,38(4):725-727.
[15]郭新宇,李海霞,谢妍,等.自然排卵,促排卵和超促排卵状态下小鼠卵巢组织中生长分化因子-9(GDF-9)的表达[J].生殖与避孕,2013,33(001):1-5.
[16]邱冉冉.护卵汤对GnRHa超排卵大鼠卵巢超微结构及体细胞凋亡的影响[D].长沙:湖南中医药大学,2013.
[17]申可佳.护卵汤对GnRHa超排卵大鼠卵泡发育的影响研究[D].长沙:湖南中医药大学,2012.
[18]Sifer C, Blanc-Layrac G, Bringuier AF, et al. Effects of aGonadotropin-Releasing Hormone agonist and Follicle StimulatingHormone on the incidence of apoptosis in human luteinized granulosacells[J]. Eur J Obstet Gynecol Reprod Biol.,2003,110(1):43-48.
[19]Otsuka F, Shimasaki S. A negative feedback system between oocyte bonemorphogenetic protein15and granulosa cell kit ligand: its role inregulating granulosa cell mitosis[J]. Proc Natl Acad Sci USA.,2002,999(12):8060-8065.
[20]Clavero A, Castilla JA, Nú ez AI, et al. Apoptosis in human granulosacells after induction of ovulation in women participating in anintracytoplasmic sperm injection program[J]. Obstetrics&Gynecologyand Reproductive Biology,2003,110:181-185.
[21]Kaneko T, Saito H, Takahashi T, et al.Effects of controlled ovarianhyperstimulation on oocyte quality in terms of the incidence of apoptoticgranulosa cells[J]. J Assist Reprod Genet.,2000,17(10):580-585.
[22]Hutt KJ, McLaughlin EA, Holland MK. Kit ligand and c-Kit have diverseroles during mammalian oogenesis and folliculogenesis[J]. Mol HumReprod.,2006,12(2):61-69.
[23]辛明蔚,李玛建,何军琴.中医药在体外授精-胚胎移植中的应用思路[J].安徽中医学院学报,2004,29(4):31-33.
[24]申可佳,尤昭玲.中医药改善超排卵周期卵泡发育的研究思路[J].湖南中医药大学学报,2012,32(4):3-5.
[25]金方.何嘉琳谈在辅助生育技术中中医药的应用[J].北京中医,2004,23(6):329.
[26]傅萍,楼毅云.中医药在体外受精-胚胎移植技术中的辨治思路[J].中华中医药学刊,2009,27(9):1870-1873.
[27]连方.中医药在生殖领域的研究[C].国际生殖医学新技术研讨会资料汇编,2011.
[28]杨海虹,高宝辉,金慧佩.小剂量雌激素对诱导排卵增殖期子宫内膜的影响[J].中国妇幼保健,2005,20(15):1447-1449.
[29]郭秋琼,高飞雁.小剂量雌激素对克罗米芬诱导排卵增殖期子宫内膜的影响[J].实用临床医学,2006,7(4):89-91.
[30]芦小娟.戊酸雌二醇对克罗米芬周期中子宫、生殖激素及妊娠率的影响[D].西安:第四军医大学,2003.
[31]程宽,冷维春,焦晓光.氯米芬加雌激素对子宫内膜雌孕激素受体影响的临床观察[J].中国妇幼保健,2005,20(5):625-626.
[32]秦丽洁,韩英林,于小予,等.氯米芬加倍美力对子宫内膜雌孕激素受体影响的临床观察[J].中国妇幼保健,2005,20(22):2931-2932.
[33]李春,黄朝霞,程静,等.不同雌激素对克罗米芬促排卵周期子宫内膜、子宫动脉血流及临床妊娠率的影响[J].中国妇幼保健,2007,22(36):5195-5197.
[34]谭晓珊,秦娟,谭兵兵.小剂量阿司匹林对薄型子宫内膜发育的影响[J].中国综合临床,2006,22:29-31.
[35]杨海虹,叶碧绿,吕杰强,等.氯米芬合用阿司匹林对子宫内膜发育和子宫血流的影响[J].实用妇产科杂志,2005,2;21(2):114-115.
[36]李宝兰.天然雌激素加小剂量阿司匹林对促排卵子宫内膜发育60例临床观察[J].中国妇幼保健,2007,22:1906.
[37]李春洋,程静,黄朝霞,等.戊酸雌二醇与阿司匹林联合应用对诱发排卵周期子宫内膜发育及临床妊娠率的影响[J].温州医学院学报,2007,11;37(6):556-558.
[38]彭莲红,欧阳瑞霞,易清.阿司匹林对氯米芬诱导排卵患者子宫内膜容受性的影响[J].山东医药,2008,48(16):38.
[39]丁卫,刘嘉茵,钱云,等.低剂量阿司匹林在辅助生育技术中的应用[J].生殖医学杂志,2003,6;12(3):156-159.
[40]Hsieh YY, Tsai HD, Chang CC, et al. Low-dose aspirin for infertilewomen with thin endometrium receiving intrauterine insemination: aprospective, randomized study[J]. J Assist Reprod Genet.,2000,3;17(3):74-77.
[41]Dickey RP, Olar TT, Taylor SN, et al. Relationship of endometrialthickness and pattern to fecundity in ovulation induction cycles: effect ofclomiphene citrate alone and with human menopausal gonadotropin[J].Ferti Steril.,1993,4;59(4):756-760.
[42]郭玉琪,刘义,丁玉莲,等.小剂量阿司匹林在诱发排卵中对子宫内膜组织形态学的影响[J].生殖医学杂志,2008,8;11(4):203-205.
[43]Ruopp MD, Collins TC, Whitcomb BW, et al. Evidence of absence orabsence of evidence? A reanalysis of the effects of low-dose aspirin in invitro fertilization[J]. Fertil Steril.,2008,6;90(1):71-76.
[44]Dirckx K, Cabri P, Merien A, et al. Does low-dose aspirin improvepregnancy rate in IVF/ICSI? A randomized double-blind placebocontrolled trial[J]. Hum Reprod.,2009,4;24(4):856-860.
[45]Helms AK, Kittner SJ. Pregnancy and stroke[J]. CNS Spectr.,2005,7;10(7):580-587.
[46]Streck RD, Kumpf SW, Ozolins TR, et al. Rat embryos express transcriptsfor cyclooxygenase-1and carbonic anhydrase4,but not forcyclooxygenase-2,during organogenesis[J]. Birth Defects Res B DevReprod Toxicol.,2003,2;68(1):57-69.
[47]Hoozemans DA, Schats R, Lambalk CB, et al. Human embryoimplantation:current knowledge and clinical implantations in assistedreproductive technologies[J]. Reprod Biomed Online.,2004,12;9(6):692-715.
[48]Loeb L. Ueber die experimentelle Erzeugung von Knoten vonDeciduagewebe in dem Uterus des Meerschweinchens nachstattgefundener copulation[J]. Centrbl. allg. Path. path. Anat.,1907,18:563.
[49]罗国群,邓伟芬,马文敏.机械刺激子宫内膜对内膜形态不良者IVF-ET临床结局的影响[J].生殖与避孕,2012,2;32(2):139-142.
[50]Dekel N, Gnainsky Y, Granot I, et al. Inflammation and implantation[J].Am J Reprod Immunol.,2010,1;63(1):17-21.
[51]王瑶,冯云,牛志宏,等.子宫内膜轻创对着床相关因子及IVF妊娠结局影响的研究[J].生殖与避孕,2007,7;27(7):454-462.
[52]Lessey BA, Gui Y, Apparao KB, et al. Regulated expression ofheparin-binding EGF-like growth factor (HB-EGF) in the humanendometrium: a potential paracrine role during implantation[J]. MolReprod Dev.,2002,8;62(4):446-455.
[53]Karpovich N, Chobotova K, Carver J, et al. Expression and function ofinterleukin-11and its receptor alpha in the human endometrium[J]. MolHum Reprod.,2003,2;9(2):752-801.
[54]李权,谭晓珊,王丽,等.机械刺激对C型子宫内膜种植窗期组织形态学的影响[J].贵州医药,2007,8;31(8):678-681.
[55]李蓉,钟凯,卢丽华,等.胚胎移植周期机械刺激子宫内膜提高临床妊娠率[J].生殖医学杂志,2007,12;13(6):342-345.
[56]葛明晓,张金玉,李海霞,等.搔刮术对子宫内膜形态不良患者体外受精-胚胎移植临床结局的影响[J].中华妇产科临床杂志,2012,9;13(5):352-354.
[57]胡玥玥,黄晓卉,江胜芳,等.子宫内膜浅搔刮对胚胎移植周期结局的影响[J].中国优生与遗传杂志,2012,20(10):121-122.
[1]张玉珍主编.中医妇科学[M].北京:中国中医药出版社,2002:364.
[2]Amato G, Izzo A, Tucker A, et al. Insulin-like growth factor bindingprotein-3reduction in follicular fluid in spontaneous and stimulatedcycles[J]. Ferti1Steril.,1998,70(1):141-144.
[3]石红.卵巢旁分泌与自分泌[J].中国实用妇科与产科杂志,2001,17(4):241.
[4]龚非力主编.医学免疫学[M].第二版.北京:科学出版社,2004:61.
[5]Spangelo BL, Farrimond DD, Pompilius M, et al. Interleukin-1beta andthymic peptide regulation of pituitary and glial cell cytokine expression andcellular proliferation[J]. Ann N Y Acad Sic.,2000,917:597-607.
[6]龚守良,赵勇,刘淑春. IL-1对垂体促性腺细胞及甲状腺轴分泌功能的短期效应[J].白求恩医科大学学报,2005,3(1):7-8.
[7]Morita Y, Perez GI, Maravei DV, et al. Targeted expression of Bcl-2inmouse oocytes inhibits ovarian follicle atresia and prevents spontaneous andchemotherapy-induced oocyte apoptosis in vitro [J]. Mol Endocrinol.,1999,13(6):841-850.
[8]Petroff MG, Petroff BK, Pate JL. Expression of cytokine messenger ribonucleic acids in the bovine corpus luteum[J]. Endocrinology,1999,140:1018-1021.
[9]李庆雷,倪江.细胞因子对卵巢功能的调节作用[J].生理科学进展,2000,31(4):361.
[10]Grasso G, Asano A, Minagawa T, et al. Immunohistochemical localizationof interferon-gamma in normal human ovary[J]. Gynecol Endocrinol.,1994,8(3):161-168.
[11]王秀霞,易晓芳,何丽霞.卵泡液中肿瘤坏死因子-α和干扰素-γ水平对体外受精结局的影响[J].中国实用妇科与产科杂志,2009,25(11):859-860.
[12]王秀霞,王天任,易晓芳,等.卵泡液中TNF-CC和IFN-γ与卵丘颗粒细胞凋亡关系的探讨[J].生殖与避孕,2010,30(8):519-522.
[13]Braat DD, Schoemaker R, Schoemaker J. Life table analysis of fecundityin intravenously gonadotropin-releasing hormone-treated patients withnormogonadotropic and hypogonadotropic amenorrhea [J]. Fertil Steril.,1991,56(2):265-272.
[14]胡静.卵巢内调节因子在多囊卵巢综合征发病中的作用[J].国外医学计划生育分册,2003,22(4):229.
[15]王国云,姜虹,晁岚,等.人卵丘颗粒细胞凋亡与卵子发育潜能关系的研究[J].生殖与避孕,2006,26(2):91-94.
[16]李芳,郑月慧,肖秋香,等.肿瘤坏死因子–α与卵子生成[J].生殖与避孕,2007,27(7):479-483.
[17]Chen HL, Marcinkiewicz JL, Sancho-Tello M, et al. Tumor necrosisfactor-alpha gene expression in mouse oocytes and follicular cells [J]. BiolReprod.,1993,48(6):707-714.
[18]Lee KS, Joo BS, Na YJ, et al. Relationships between concentrations oftumor necrosis factor-alpha and nitric oxide in follicular fluid and oocytequality[J]. J Assist Reprod Genet.,2000,17:222-228.
[19]路帅.补肾法、疏肝法对排卵障碍模型大鼠卵巢细胞因子影响的比较研究[D].石家庄:河北医科大学,2010.
[20]张昌军,王华,周艳梅.白细胞介素6及肿瘤坏死因子对体外受精-胚胎移植结局的影响[J].郧阳医学院学报,2003,22(5):257-261.
[21]Chae HD, Hong SH, Hong SH, et al.Influence of tumor necrosisfactor-alpha on estradiol, progesterone, insulin-like growth factor-II,andinsulin-like growth factor binding protein-1,2, and3in cultured humanluteinized granulosa cells[J]. Eur J Obstet Gynecol Reprod Biol.,2007,131:176-181.
[22]Wuttke W, Pitzel L, Knoke I, et al. Immune-endocrine interactionsaffecting luteal function in pigs[J]. J Reprod Fertil Suppl.,1997,52:19-29.
[23]J S Richards, D L Russell, R L Robker, et al. Molecular mechanism ofovulation and luteinization[J]. Mol Cell Endocrinol.,1998,145:47-54.
[24]Tamura K, Tamura H, Kumasaka K, et al. Ovarian immune cells expressgranulocyte-macrophage colony-stimulating factor (GM-CSF) duringfollicular growth and luteinization in gonadotropin-primed immaturerodents[J]. Mol Cell Endocrinol.,1998,142:153-163.
[25]Cohen PE, Zhu L, Pollard JW. Absence of colony stimulating factor-1inosteopetrotic (csfmop/csfmop) mice disrupts estrous cycles andovulation[J]. Biol ReProd.,1997,56:110-118.
[26]Salnassi A, Zhang L. Expression Pattetns of GM-CSF in human ovarianfollicular fluid and serum[J]. Hum Reprod.,2001,16:203.
[27]王喜艳,徐邦生,高银峰,等. BMP-6对卵巢功能和生殖能力作用的研究进展[J].生殖与避孕,2009,11:621.
[28]Mery L, Lefevre A, Benchaib M, et al. Follicular growth in vitro:detection of growth differentiation factor9(GDF9) and bonemorphogenetic protein15(BMP15) during in vitro culture of ovinecortical slices[J]. Mol Reprod Dev.,2007,74(6):767-774.
[29]Liu L, Rajareddy S, Reddy P, et al. Infertility caused by retardation offollicular development in mice with oocyte-specific expression ofFoxo3a[J]. Development,2007,134(1):199-209.
[30]Nilsson EE, Skinner MK. Kit ligand and basic fibroblast growth factorinteractions in the induction of ovarian primordial to primary follicletransition[J]. Mol Cell Endocrinol.,2004,214(1-2):19-25.
[31]Dong J, Albertini DF, Nishimori K, et al.Growth differentiation factor-9isrequired during early ovarian folliculogenesis[J]. Nature,1996,383:485-486.
[32]Hreinsson JG, Scott JE, Rasmussen C, et al. Growth differentiationfactor-9promotes the growth, development，and survival of human ovarianfollicles in organ culture[J]. J Clin Endocrinol Metab.,2002,87:316-321.
[33]Galloway SM, Gregan SM, Wilson T, et al. Bmp15mutations and ovarianfunction[J]. Mol Cell Endocrino.,2002,191:15-18.
[34]Matzuk MM. Revelations of ovarian follicle biology from gene knockoutmice[J]. Mol Cell Endocrinol.,2000,163(1-2):61-62.
[35]苗竹林,王自能,郑佩娥,等.生长分化因子-9在大鼠卵巢中的表达[J].暨南大学学报(医学版),2005:195-198.
[36]李爽,夏阳,夏天.补肾调冲方对半乳糖致POF大鼠始基卵泡募集及卵泡闭锁相关因子GDF-9表达的影响[J].辽宁中医杂志,2011,38(11):2267-2270.
[37]曲中玉.生长分化因子-9与FOXL2在卵巢组织中的表达与调控研究[D].济南:山东大学,2006.
[38]Cocquet J, Pailhoux E, Jaubert F, et al. Evolution and expression ofFOXL2[J]. J Med Genet.,2002,39(12):916-921.
[39]Weenen C, Laven JS, Von Bergh AR, et al. Anti-Müllerian hormoneexpression pattern in the human ovary: potential implications for initialand cyclic follicle recruitment[J]. Mol Hum Reprod.,2004,10(2):77-83.
[40]Durlinger AL, Gruijters MJ, Kramer P, et al. Anti-Müllerian hormoneinhibits initiation of primordial follicle growth in the mouse ovary[J].Endocrinology,2002,143(3):1076-1084.
[41]李键,乔杰.抗苗勒氏管激素在卵泡形成中的作用[J].中国优生与遗传杂志,2007,15(10):1.
[42]Mather JP, Moore A, Li RH.Activins, inhibins，and follistatins: furtherthoughts on a growing family of regulators[J]. Proc Soc Exp Biol Med.,1997,215(3):209.
[43]夏天.补肾调冲方对大鼠卵巢颗粒细胞增殖与分泌及其相关基因表达的影响[D].天津:天津中医药大学,2005.
[44]Ling N, Ying SY, Ueno N, et al. Isolation and partial characterization of aMr32,000protein with inhibin activity from porcine follicular fluid[J].Proc Natl Acad Sci USA.,1985,82(21):7217-7221.
[45]Roy SK, Greenwald GS. Immunohistochemical localization of epidermalgrowth factor-like activity in the hamster ovary with a polyclonalantibody[J]. Endoerinology,1990,126:1309-1317.
[46]赵明,方芳. EGF对大鼠卵巢颗粒细胞增殖与分化影响的研究[J].生理学报,1993,45(3):207-214.
[47]Procházka R, Srsen V, Nagyová E, et al. Developmental regulation ofeffect of epidermal growth factor on porcine oocyte-cumulus cellcomplexes: nuclear maturation, expansion, and F-actin remodeling[J]. MolReprod Dev.,2000,56:63-73.
[48]Wu J, Zhang L, Liu P. A new source of human oocytes: preliminary reporton the identification and maturation of human preantral follicles fromfollicular aspirates[J]. Hum Reprod.,1998,13:2561-2563.
[49]Reeka N, Berg FD, Brucker C. Presence of transforming growth factoralpha and epidermal growth factor in human ovarian tissue and follicularfluid[J]. Hum Reprod.,1998,13(8):2199-2205.
[50]许程洁,王鑫泉,陈毅斐,等.卵巢颗粒细胞激素与成纤维细胞生长因子的信号交流[J].四川生理科学杂志,2011,33(3):123-124.
[51]于元松,谭景和.卵巢中的胰岛素样生长因子系统[J].生理科学进展,2002,33(2):31.
[52]Spicer LJ, Santiago CA, Davidson TR, et al. Follicular fluidconcentrations of free insulin-like growth factor (IGF)-I during folliculardevelopment in mares[J]. Domest Anim Endocrinol.,2005,29(4):573-581.
[53]陈丹清,石一复.胰岛素样生长因子-I及其结合蛋白-I对促超排卵周期卵泡发育的影响[J].中华妇产科杂志,2000,35:719-721.
[54]Nilsson EE, Kezele P, Skinner MK. Leukemia inhibitory factor (LIF)promotes the primordial to primary follicle transition in rat ovaries[J]. MolCell Endocrinol.,2002,188(1-2):65-73.
[55]洪俊君,王子玉,王锋.干细胞因子在卵泡发育过程中的作用[J].细胞生物学杂志,2006,28:667-670.
[56]Sette C, Dolci S, Geremia R, et al. The role of stem cell factor and ofalternative c-kit gene products in the establishment, maintenance andfunction of germ cells[J]. Int J Dev Biol.,2000,44(6):599-608.
[57]Wang J, Roy SK. Growth differentiation factor-9and stem cell factorpromote primordial follicle formation in the hamster: modulation byfollicle-stimulating hormone[J]. Biol Reprod.,2004,20(3):577-585.
[58]Klinger FG, De Felici M. In vitro development of growing oocytes fromfetal mouse oocytes: stage-specific regulation by stem cell factor andgranulosa cells[J]. Dev Biol.,2002,244(1):85-95.
[59]严杰,乔杰.干细胞因子及其受体在卵泡早期发育中的作用[J].生殖与避孕,2008,12(12):739-743.
[60]董艳敏.干细胞因子与生殖医学的关系[J].中国性科学,2008,17(4):18-22.
[61]王桂红.干细胞因子在女性生殖过程中作用的初步研究[D].西安:第四军医大学,2003.
[62]Anasti JN, Kalantaridou SN, Kimzey LM, et al. Human follicle fluidvascular endothelial growth factor concentrations are correlated withluteinization in spontaneously developing follicles[J]. Hum Reprod.,1998,13(5):1144-1147.
[63]邢福旗,梁卫华,陈士岭.血管内皮生长因子在人卵巢和子宫内膜上的表达[J].第一军医大学学报,2000,20(5):453-455.
[64]Hornung D, Lebovic DI, Shifren JL, et al. Vectorial secretion of vascularendothelial growth factor by polarized human endometrial epithelialcells[J]. Fertil Steril.,1998,69(5):909-915.
[65]Sugino N, Kashida S, Takiguehi S, et al. Expression of vascularendothelial growth factor and its receptors in the human corpus luteumduring the menstrual cycle and in early pregnancy[J]. Clin EndoerinolMetab.,2000,85(10):3919-3924.