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雷公藤及其提取物治疗自身免疫性甲状腺炎的实验研究
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摘要
目的:
     观察雷公藤及其提取物对实验性自身免疫性甲状腺炎的作用效果及机理。
     方法:
     1.高碘水配制
     称取碘化钾0.64g溶于1L蒸馏水中,避光储存。
     2.分组造模及给药
     所有小鼠随机分为5组:即正常对照组(等量NS)、EAT模型组(等量NS)、雷公藤组(3.3g/kg)、雷公藤多甙片组(10mg/kg)、雷公藤甲素组(50μg/kg),每组10只。采用皮下多点注射TG抗原加高碘的方法制作EAT小鼠模型。除正常对照组外,各组小鼠于皮下多点注射含PTg(0.25mg/ml)完全弗氏佐剂抗原共0.2ml,连续2周,每周一次。第3周起每只小鼠皮下注射PTg(0.25mg/ml)不完全弗氏佐剂抗原0.2ml,连续3周,每周一次。同时,各给药组按0.1ml/10g体重灌胃给药,正常对照组与模型对照组给予等体积生理盐水,末次给药后禁食24h。
     3.取材
     实验结束后小鼠眼眶取血,室温放置20min,2500r/min离心10min,取血清。采用放射免疫法测定T3、T4、FT3、FT4,TGAb、TMAb;甲状腺病理改变情况的影响;CD4+、 CD8+T淋巴细胞的比值的影响;甲状腺中Fas、Fas L改变情况的影响;甲状腺中caspase3改变情况的影响
     结果:
     1. EAT小鼠模型对照组血清T3、T4、FT3、FT4水平都高于正常组,差异有统计学意义(P<0.01)。与模型组比较,雷公藤、雷公藤多甙、雷公藤甲素三组的血清甲状腺激素都下降。雷公藤与雷公藤多甙两组的FT3,FT4,T3,T4下降存在显着性差异;雷公藤甲素组FT3,FT4,T4的下降存在显着性差异,T3差异性不显着。雷公藤、雷公藤多甙、雷公藤甲素三组的血清甲状腺激素都下降。雷公藤多甙组的TMAb、TGAb数值最低,下降最显着。
     2.模型组CD4+高于正常组、CD8+低于正常组,有显着性差异(p<0.01); CD4+/CD8+高于正常组,有显着性差异(p<0.01)。与模型组比较,雷公藤、雷公藤多甙、雷公藤甲素三组的CD4+比例下降、CD8+比例上升、CD4+/CD8+下降,且存在显着性差异。
     3.EAT小鼠模型组甲状腺中Fas、Fas-L表达水平都高于正常组,与正常组相比,差异有统计学意义(P<0.01)。与模型组比较,雷公藤、雷公藤多甙、雷公藤甲素三组的Fas、Fas-L都公藤多甙组的Fas、Fas-L数值最低,下降最显着。
     4.EAT小鼠模型组甲状腺中caspase3表达水平都高于正常组,与正常组相比,差异有统计学意义(P<0.01)。与模型组比较,雷公藤、雷公藤多甙、雷公藤甲素三组的caspase3都下降,存在显着性差异。雷公藤多甙组的caspase3数值最低,下降最显着。
     结论:
     本课题为雷公藤及其提取物临床应用于AT的治疗提供了实验依据,同时也为丰富治疗免疫性疾病中药的认识,扩展其应用提供了指导。随着人们对于AT的认识的不断深入以及中医药科学的不断发展,中药治疗AT将具有很大的发展空间和应用前景。
Purpose
     Investigate the effect and mechanism of Tripterygium and its extracts on experimental autoimmune thyroiditis.
     Method
     1. Preparation of Periodate water
     0.64g Potassium iodide dissolved in1L of distilled water, then storage it without sunlight reached.
     2. Group modeling and medicine administration
     All the small mice will separate into five groups randomly:Normal control group (striped NS), EAT model group (striped NS), Tripterygium group (3.3g/kg), Tripterygium Glycosides piece group (10mg/kg), Triptolide group (50μg/kg), n=10. Injected subcutaneously TG antigen plus periodate produced EAT mouse model. In addition to the normal control group, the mice in each group at the multiple sites subcutaneous injection of complete Freund's adjuvant containing PTg (0.25mg/ml) antigen of0.2ml, two weeks in a row, once a week. The first three weeks of each mice were injected subcutaneously PTg (0.25mg/ml) incomplete Freund's adjuvant antigen0.2ml, for three consecutive weeks, once a week. At the same time, each dose group0.1ml/10g weight is normal control group and model control group was given an equal volume of saline, fasted for24h after the last administration.
     3. Coverage
     After the end of the experiment, mice orbital blood will take out at room temperature for20min,2500r/min centrifugal10min, then take out the blood serum. Measured by radioimmunoassay T3, T4, FT3, FT4, TGAb, TMAb; thyroid pathological changes in the situation; CD4+, CD8+T lymphocyte ratio impact; thyroid in Fas, Fas L change the situation; thyroid caspase3change the impact of the situation.
     Result
     1. EAT mice model control group, blood serum T3, T4, FT3, FT4is higher than the normal group, the difference was statistically significant (P<0.01). Compared with model group, Tripterygium, Tripterygium glycosides, Tripterygium triptolide blood serum thyroid hormone are declined. Tripterygium and Tripterygium Glucosides two groups of FT3, FT4, T3, T4decline with a significant difference; Tripterygium Triptolide group FT3, FT4, the decline in the presence of T4significant difference, however the difference of T3was not significant. Wilfordii, Tripterygium glycosides, Tripterygium triptolide three groups of blood serum thyroid hormone declined. Tripterygium glycosides group TMAb, TGAb has the lowest value, which dropped the most significant.
     2. Model group, CD4+is higher than the normal group, CD8+is lower than the normal group, there is a significant difference (p<0.01); CD4+/CD8+is higher than the normal group, a significant difference (p<0.01). Group compared with the model group, Tripterygium, Tripterygium glycosides, Tripterygium Triptolide prime CD4+decline in the proportion, CD8+risen, CD4+/CD8+decreased, and there are significant differences.
     3. EAT mice model group thyroid Fas, Fas-L expression levels are higher than the normal group, compared with the normal group, the difference was statistically significant (P<0.01). Group compared with the model group, Tripterygium, Tripterygium glycosides, Tripterygium Triptolide prime Fas, Fas-L are public rattan polyglycoside group Fas, Fas-L lowest value, dropped the most significant.
     4. EAT mice model of thyroid caspase3expression levels are higher than the normal group, compared with the normal group, the difference was statistically significant (P<0.01). Group compared with the model group, Tripterygium, Tripterygium glycosides, Tripterygium Triptolide prime caspase3are down, there is a significant difference. Tripterygium glycosides the group caspase3numerical minimum, dropped the most significant.
     Conclusion
     The subject is applied to the Tripterygium and its extract on clinical AT treatment to provide an experimental basis, as well as a rich understanding of Chinese medicine treatment of autoimmune diseases, extend its application to provide guidance. With the continuous development for people to further understand the AT as well as in pharmaceutical science, Chinese medicine treatment of AT will have more development spaces and application prospects.
引文
[1].Eber O,Langsteger W.Clinical aspects of autoimmune thyroid disease.Acta MedAustriaca(Abstract),1994, 21(1):1-7
    [2]Singer PA. Thyroiditis:acute, subacute, and chronic.Med Clin North Am,1991,75:61.
    [3]Lyerly HK. Thyroiditis. In:Sabiston DC, Lyerly HK,eds. Textbook of surgery.15th ed. Philadelphia: WBSaunders Company,1997,623
    [4]Feldt-Rasmussen U. Analytical and clinical perfor-mance goals for testing autoantibodies to thyropero-xidase, thyroglobulin, and thyrotropin receptor. ClinChem,1996,42:160.
    [5]殷志强,沈义琴,邝耀麟320例甲状腺细针细胞学检查的临床分析.上海第二医科大学学报,1998,18:51.
    [6]Volpe R.Etiology,pathogenesis,and clinical aspects ofthyroiditis.Pathol Annu,1978,13:399-413
    [7]Nguyen GK,Ginsherg J,Crockford PM,et al.Hashimoto's thyroiditis:cytodiagnostic accuracy and pitfalls.Diagn cytopathol,1997,16(6):531.
    [8]徐惠琴,杨桂芳,林利.桥本甲状腺炎的细针吸取细胞学诊断及鉴别.湖北医科大学学报,1998,5(1):19-21
    [9]任玉波,梁凤泉.细针活检细胞学检查对桥本氏病的诊断意义[J].诊断病理学杂志,1998,8(6):505
    [10]刘新民,潘长玉,张达青,等.实用内分泌学.北京:人民军医出版社,2004,第三版:269.
    [11]白耀.自身免疫性甲状腺炎的研究进展.国外医学内分泌学分册,2003;23(6)367-369.
    [12].Brix TH,Kyvik KO,Hegedus L.A population-based study of chronic autoimmune hypothyroidism inDanish twins.J Clin Endocrinol Metab,2000,85(2):536-539
    [13]徐烷白.自身免疫性甲状腺病的遗传及易感性研究进展.国际内科学杂2007:34(7):422-425.
    [14]朱本章,浦丹.桥本病及其边缘疾病的再认识和处理.中国医师进修杂志,2007;30(8):1-3.
    [15]Mosmann TR,Cherwinski H,Bond MW,et al.Two Types of Murine helper T Cell Clone.I.Definition According to Profiles of Lymphokine Activities and Secreted Proteins.[J]J Immunol 1986; 136:2348-2357.
    [16]Mosmann TR,Coffman RL.TH1 and TH2 Cells:Different patterns of Lymphokine SecretionLead to Different Functional Properties.[J]Annu Rev Immunol 1989;7:145-173.
    [17]Chen KM,Wei YZ,Sharp GC,et al.Decreasing TNFaResults in Less Fibrosis and EarlierResolution of Granulomatous Experimental Autoimmune Thyroiditis.[J]Leukoc Biol.2007;81(1):306-314.
    [18]Chen RH,Chang CT.Proinflammatory Cytokine Gene Polymorphisms among Hashimoto'sThyroiditis Patients.[J]Clin Lab Anal.2006;20(6):260-265.
    [19]Ito C,Watanabe M,Okuda N,et al.Association Between the Severity of Hashimoto'sdisease andtheFunctional+874AA/PolymorphismintheInterferon-γ Gene.[J]EndocrineJournal.2006;53(4),473-478.
    [20]Phelps E,Wu P,Bretz J,et al.Thyroid cell apoptosis.A new understanding of thyroid autoimmunity. Endocrinol Metab Clin North Am,2000,29(2):375-388
    [21]Okamura K,Sato K,Jkenoue Jl.et al.Ptunary hypothyroidism manifestated in childhood with specialreferencetovarioustypesreversiblehypothyroidism.EurJEndocrinoI.1994,131(2):131-137
    [22]Nagata S.Golstein P.The Fas death factorlJ2.Science,1995,267:1449-1456.
    [23]Peng SL,Robert ME,Hayday AC,et al.A tumor2suppressorfunction for Fas (CD95)revealed inTcell2deficientmicel [J].J Exp Med,1996,184:1149-1154.
    [24]Badley AD,Dockrell D,Simpson M,et al.Macrophage2depen2dent apoptosis of CD4+Tlymphocytes fromHIV2infected indi2viduals is mediated by FasL and tumor necrosis factorl [J].JExp Med,1997,185: 55-64.
    [25]ThornberryNA,Lazebnik Y Caspases:enemieswithinl[J].Science,1998,281:1312-1316.
    [26]Giordano C,Stassi G,Maria RD,et al.Potential involvement ofFas and its ligand in the pathogenesis ofHashimoto.s thyroid2itisl [J].Scinece,1997,275:960-963.
    [27]StrokesTA,Rymaszewski M,Arscott PL,et al.Constitutive ex2pression of FasL in thyrocytesl[J].Science, 1998,279:2015-2025.
    [28]Kotani T,Aratake Y,Hirai K,et al.Apoptosis in thyroid tissuefrom patientswith Hashimoto.s thyroiditisl [J]. Autoimmunity,1995,20:231-236.
    [29]Hall R. Changing iodine intake and the effect on thyroid disease [J]. British Med J,1987,294:720-722
    [30]Laurberg P, Iodine intake-what are we aiming at? (editorial; comment) [J]. Endocridol Metab,1994,79: 17-19
    [31]Berg G and Ekholm R. Electron microscopy of low iodinated thyroglobulin molecules.Biochim Biophys Acta 1975,386:422
    [32]Many MC, Maniratunga S, Varis 1, et al. Two-step development of Hashimoto-like thyroiditisin genetically autoimmune prone non-obese diabetic mice:effects of iodine induced cell necrosis. J Endocrinol,1995,147:311-320
    [33]徐春,白耀,崔莲仙,等.慢性淋巴细胞性甲状腺炎与HLA-DQ位点基因的相关性分析.中华内科杂志,1998,37(6):393-396
    [34].Rose NR,Rasody L,Saboori AM,et al.Linking iodine autoimmune thyroiditis.Environ HealthPerspect (Abstract),1999,107 suppl5:749-752
    [35]Palazzo FF,Hammond LJ,Goode AW,et al.Death of the autoimmune thyrocyte:it is pushed or does itjump?Thyroid,2000,10(7):561-572
    [36]龚益,施秉银,崔燕,等.自身免疫性甲状腺病的病因探讨.西安交通大学学报(医学版),2005;26(3):297-299.
    [37]Brix TH, Hansen PS, Kyvik K0, et al. Cigarette smoking and risk ofclinically overt thyroid disease [J].Arch Intern Med,2000,160(5):661-666.
    [38]Winsa B, Adami HO, Bergstrom R, et al.Stressful life events andGraves'disease [J].Lancet,1991,338 (8781):1475-1479.
    [39]Fardella C, Gloger S, Figueroa R, et al.High prevalence of thyroidabnormalities in a children psychiatric out patient population[J].JEndocrinol Invest,2000,23(2):102-106.
    [40]Gyory F.Lukaes G.Juhasz F,et al.Surgically treated Hashimoto's thyroiditis Acta Chillung(Abstract). 1999,38(3-4)243-247
    [41]Scopsi L,Colhni P,Sampretro G,et al.Prognostic impact of thyroid lymphocytic infiltration in patients with medullary thyroid carcinoma.Thyroid,1996,6(6):613-617
    [42]Canton A,de Fabregas O,Tintore M,et al.Encephalopathy associated to autoimmune thyroid disease:amore appropriate term for an underrestumated condition?J Neurol Sci.2000.176(1):65-69
    [43]Guimareas VC,Qumtans J,Fisfalen ME,et al.Suppression of development of experimental autoimmunethyroiditis by oral administration of thyroglobulin.Endocrinology,1995,138(8):3353-3359
    [44]Prud'hommeGJ.Gene therapy of autoimmune disease with vectors encoding regulatory cytokines orinflammatory cytokine inhibitors.J Gene Med,2000,2(4):222-232
    [45]Heufelder AE,Goellner JR,Bahn RS,et al,Tissue cosinophilia and cosinophil degranulation in Riedel's invasive fibrous thyroiditis J Clin Endocrinol Metab,1996,81(3);977-984
    [46]朱霞,黄道中.桥本甲状腺炎的超声表现及其病理学基础.中国临床医学影像杂志,2006;17(11):647-649.
    [47]中华医学会.临床诊疗指南内分泌及代谢性疾病分册.北京:人民卫生出版社,2005,第一版:24-25.
    [48]顾明君,吴文雅,方瑾,等.甲状腺素及甲状腺内注射地塞米松治疗伴亚临床甲减的桥本甲状腺炎.第二军医大学学报,2004,25(9):977-980.
    [49]赵文娟,闰胜利,王颜刚,等.利美达松局部注射辅助治疗桥本甲状腺炎的效果.青岛大学医学院学报,2004,40(3):214-215.
    [50]吴庆强,窦连军,杜振玲等,超声引导下经甲状腺介入氟美松治疗桥本甲状腺炎.临床荟萃,2006,21(3):195-196.
    [51]段学宁.甲状腺全切除术治疗顽固性桥本甲状腺炎的效果探讨[J].中国临床医生,2003,31(1):26-28
    [52]邓万凯,孙学华.甲状腺桥本病诊断与治疗体会[J].河南肿瘤学杂志,2001,14(4):282-283
    [53]张仕益,等.慢性淋巴细胞性甲状腺炎19例分析[J].美国中华临床医学杂志,2005,7(3)251-252
    [54]谭新.中医外科学,北京:人民卫生出版社,1999,10月,第一版:302-308
    [55]华川,许芝银.温瘦消治疗桥本氏甲状腺炎的实验研究.江苏中医药2003;24(8):52-54
    [56]唐汉钧.唐汉钧谈外科病[M].上海:上海科技教育出版社,2004:82
    [57]陈贵延,杨思澎.实用中西医结合诊断治疗学[M].北京中国医药科技出版社,1995,5:135
    [58]刘巧格.中药甲宁方联合甲状腺片治疗桥本氏甲状腺炎临床疗效分析[J].中华实用中西医杂志.2004,38(10):30-32
    [59]马德权.桥本氏甲状腺炎继发甲状腺功能减退的中医治疗[J].天津中医药.2005,18(20):1299-1300
    [60]伍锐敏.中医辨证为主治疗儿童桥本氏病例临床观察[J].中医杂志.2003,44(11):843-845
    [61]庞洁.中药加小剂量甲状腺片治疗桥本氏甲状腺炎例临床观察[J].中医杂志.2001,42(9):543-545
    [62]谢培凤.中西医结合治疗桥本甲状腺肿的临床研究[J].中国临床保健杂志.2005,78(3):198-200
    [63]聂有智,王春勇.小柴胡汤加味治疗桥本氏甲状腺炎50例[J].山东中医药大学学报.2005,29(6):451452
    [64]方邦江等.陈如泉运用活血消痹汤治疗慢性淋巴细胞性甲状腺炎经验[J].中医杂志.2002)43(6):419
    [65]高国宇.中医药诊治桥本氏甲状腺炎理念探讨[J].河北中医,2006,28(3):191-192
    [66]许芝银.甲状腺疾病中医治疗[J].江苏:江苏科学技术出版社.2002,10:167
    [67]陈如泉.慢性淋巴性甲状腺炎30例临床分析及辨证治疗.现代中医杂志[J]1993,7:1
    [68]伍税敏等.桥本氏病56临床治疗报告.中医杂志[J],1992;5:30-33
    [69]卑其新.试论桥本氏病的辨证论治.全国第三届中医甲状腺病学术交流会论文集,1993:69
    [70]]黄庆仪.五加双参片对自身免疫性甲状腺炎TGA,TMA的影响[[J].甘肃中医,2001,14(3):86-88
    [71]熊曼琪,邓兆智.内分泌科专病与风湿病中医临床诊治[M].北京:人民卫生出版社,2000,9:92
    [72]堪剑飞.现代中医内分泌学[M].上海:上海医科大学出社,1995:261
    [73]陶冬青,杨家耀.浅谈桥本氏病发生发展与中医肝肾的关系[J].江苏中医药,2005126(6):5-6
    [74]吴凤霞.甲状腺疾病中西医诊疗学[M].北京中国中医药出版社,2000,5:82
    [75]吴晓霞,贾红声.许芝银教授治疗甲状腺疾病经验[J].河北中医,2001,23(11):131-133
    [76]张阎珍.80例甲状腺结节的中西医结合治疗.福建中医药[J].1988:1:19
    [77]刘晓轩.益气养阴消瘤法治疗桥本氏甲状腺22例.新中医[J].1999;(10):56
    [78]贾喜花.唐汉钧运用健脾化痰法治疗颈部炎性肿块经验[J]辽宁中医杂志,2002,29(3):127-128.
    [79]陈志才,许芝银.扶正消瘿法治疗自身免疫性甲状腺炎38例临床观察[J].中国中西医结合杂志,1992,12(10):611.
    [80]黄铮,唐汉钧.扶正清瘿法治疗桥本氏甲状腺炎52例[J].上海中医药杂志,2003,37(11):34.
    [81]周长泉.桂枝茯苓丸治疗桥本病疗效观察[J].河北中医,2001,23(9):691.
    [82]王孜优,张海发.理气滋肾法治疗慢性淋巴细胞性甲状腺炎133例[J].辽宁中医杂志,1989,11:17.
    [83]赵佐文,卢锦楣.中西医结合治疗桥本甲亢17例[J].实用中西医结合杂志,1996,9(8):467.
    [84]孔德明,刑玫,詹继红,等.中西医结合治疗桥本氏甲状腺炎的疗效观察[J].中国医药学报,1998,13(3):35.
    [85]胡国胜,陈汉平,侯永健,等.艾灸对桥本氏甲状腺炎患者外周血ADCC活性的作用.中国中西医结合杂志,1991,11(7):403.
    [86]胡国胜,陈汉平,侯水健,等.隔药灸治疗桥本氏甲状腺炎临床观察.中医杂志,1992,33(5):30.
    [87]王永炎.今日中医外科[M].北京:北京人民卫生出版社,2000,8:186
    [88]Mussa GC, Corrias A, Mostert M, et al.Patients with Hashimoto' sdisease treated with L-thyroxine and followed up for threeyears.J Pediatr Endocrinol Metab,1998; 11 (1):59
    [89]黄铮.从络病理论角度治疗桥本氏甲状腺炎的体会和思考.临床报道与体会杂志,2000,32(1):258
    [90]许芝银.试论桥本氏病的辨证论治.全国第三届中医甲状腺病学术交流会论文集,1993:1
    [91]程如林,高银香,叶芷宝,等.雷公藤多贰片和甲状腺片治疗慢性淋巴细胞性甲状腺炎疗效观察中国中西医结合杂志,1988,8(11):676.
    [92]孟凡江,冯莉.昆明山海棠降低桥本氏甲状腺炎患者血清TMAb和TGAb水平研究.陕西中医杂 志,1992,(5):261.
    [93]段学宁.甲状腺全切除术治疗顽固性桥本甲状腺炎的效果探讨[J].中国临床医生,2003,31(1):26-28
    [94]邓万凯,孙学华.甲状腺桥本病诊断与治疗体会[J].河南肿瘤学杂志,2001,14(4):282-283
    [95]张仕益,等.慢性淋巴细胞性甲状腺炎19例分析[J].美国中华临床医学杂志,2005,7(3)251-252
    [96]杨裕国,盛宏光.雷公藤多甙对桥本甲状腺炎的治疗作用.上海医学,1997,20(11):667-668
    [97]沈鸣,等.雷公藤多甙片治疗慢性淋巴细胞性甲状腺炎.上海医药,1996,10:21-22
    [98]李世俊,方旭.雷公藤多甙治疗慢性淋巴细胞性甲状腺炎40例[J].中国医学理论与实践2005,15(4):520
    [99]方德龄,傅冬芹.雷公藤和甲状腺片治疗桥本氏甲状腺炎[J].实用中西医结合杂志,1998,11(3):281
    [100]牟丽平.雷公藤片佐治慢性淋巴细胞性甲状腺炎25例[J].蚌埠医学院学报,2000,25(4):254-255
    [101]Kong YC, David CS. New revelations in susceptibility to autoimmune thyroiditis by the use of HZ and HLA class Ⅱ transgenic models[J].Int Rev Immunol 2000.19(6):573-585.
    [102]Carayanniotis G, Kongy C. Pathogenic thyroglobulin peptides as model antigens:insights On the induction and maintenance Of autoimmune thyroiditis[J].Int RevImmunel 2000,19(6):557-572.
    [103]Watanabe H, Inaba M, Adachi Y, et al. Experimental autoimmune thyroiditisinduced by thyroglobulin-pulsed dendritic cells[J].Autoimmunity 1999,31(4):273-282.
    [104]Nakashima M, Kong, Davies TF.The role of T cells expressing TcR V beta 13 in autoimmune thyroiditis induced by transfer of mouse thyroglobul in-activated lymphocytes:identification of two common CDR3 motifs[J].Clin Immuno Immunopathel 1996 Aug,80(2):204-210.
    [105]Wnliams WV, Kyriakos M, Sharp GC, et al. The role of cellular proliferation inthe induction of experimental autoimmune thyroiditis(EAT)in mice[J].Cell Immunol1986 Nov,103(1):96-104.
    [106]Chen K, Wei Y, Sharp GC, et al. Characterization of thyroid fibrosisin a murine model of granulomatous experimental autoimmune thyroiditis[J].J Leukoc Biol 2000Dec,68(6):828-835.
    [107]陆凤先,戴承凯,王伟,等.甲状腺抗原诱导大鼠实验性自身免疫性甲状腺炎的研究[J].中华内分泌代谢杂志,1998,14(4):252-256.
    [108]王胜军,许化溪,刘恭植,等.树突状细胞对小鼠实验性自身免疫性甲状腺炎的作用[J].中国免疫学杂志,1999,15(7):294-295.298.
    [109]丁黎,张正行,徐坚,等.昆明山海棠茎中化合物的分离及其抗炎活性[J].植物资源与环境,1992,1(4);50-53.
    [110]田荻,辛红,泰建中.雷公藤甲素对人外周血白细胞分泌促炎症性细胞因子的影响[J].上海免疫学杂志,1997,17(1);55
    [111]盛冬云,涂胜豪,陈红波.雷公藤甲素对外周血单个核细胞分泌促炎、抑炎细胞因子的影响[J].广州中医药大学学报,2006,23(6);484-486.
    [112]张欣.雷公藤甲素与雷公藤多甙治疗类风湿关节炎临床疗效对比观察[J].时珍国药研究,1994,5(3);31.
    [113]李瑞林,舒达夫主编.雷公藤的研究与临床应用[M].北京:中国科学技术出版社,1989:193-195
    [114]秦风华,谢蜀生,龙振洲.雷公藤总甙免疫抑制作用的机制[J].中国药理学通报,1991,7(6):433.
    [115].曹敏,孙荣奇,吴达俊.中药雷公藤的研究进展[J],中成药,1996,18(4):41.
    [116]田荻,辛红,秦建中.雷公藤甲素对人外周血白细胞分泌促炎症性细胞因子的影响[J],上海免疫学杂志,1997,17(1):55.
    [117]吴俊,梁晓燕,杨奕,等.雷公藤Ly-22.2'细胞的激活作用[J]。中国病理生理杂志,1996,12(1):30-31.
    [118]范祖森,曹荣华,张庆殷,等.雷公藤多甙对大鼠佐剂性关节炎治疗作用和免疫机制研究[J].中国药理学通报,1996(6):527.
    [1]Chen WLin H,Wang M. Immune intervention effects on the induction of experimental autoimmunethyroiditis[J].J Huazhong Univ Sci Technol Med Sci,2002,22 (4):343.
    [2]Barbesino G.Chiovato I.The genetics of Hashimoto S disease[J].Endocrinol Metab Clin North Am2000 Jun,29(2):357-374.
    [3]李瑞林,舒达夫主编.雷公藤的研究与临床应用[[J].北京:中国科学技术出版社出版,1989.
    [4]严士海,朱萱萱,孟达理等.麻黄多糖对EAT小鼠甲状腺激素及相关抗体水平的影响.江苏中医药,2008,40(10):111—113.
    [5]卞卫和,许芝银.扶正法在治疗甲状腺疾病中的应用[J].山西中医,1997 13(3):54.
    [6]吴晓霞,贾红声.许芝银教授治疗甲状腺疾病经验[J].河北中医,2001 23(11):813.
    [7]Leslie J. Hashimoto's thyroiditis:A disease of autoimmunity. The thyroid and its disease[M].5 th edition 1984:497-546.
    [8]Buchanan W Wet al.Association of thyrotoxicosis and autoimmune thyroiditis.Brit Med J,1961,5229(3):843.
    [9]Chen WLin H,Wang M. Immune intervention effects on the induction of experimental autoimmunethyroiditis[J].J Huazhong Univ Sci Technol Med Sci,2002,22 (4):343.
    [10]孟达理,朱萱萱,刘志辉,等.麻黄多糖对绵羊红细胞所致免疫功能低下模型小鼠溶血素抗体生成的影响(比色法).实用中医内科杂志,2007,21(1):36.
    [11]Barbesino G.Chiovato I.The genetics of Hashimoto S disease [J].Endocrinol Metab Clin North Am2000 Jun,29(2):357-374.
    [12]李瑞林,舒达夫主编.雷公藤的研究与临床应用[[J].北京:中国科学技术出版社出版,1989.
    [13].朱立平,陈学清.免疫学常用实验方法[M].北京:人民军医出版社,2000.26-28.
    [14]罗敏.分子内分泌学(基础与临床)[M].北京:人民军医出版社.2003.197-198.
    [15]张志远,郑武飞.Graves病和桥本氏甲状腺炎患者的T淋巴细胞亚群异常[J].国外医学·内分泌学分册,1984,9(3):134.
    [16].王云峰,魏枫.桥本甲状腺炎治疗前后淋巴细胞亚群及细胞学的变化[J].内蒙古医学杂志,2007,39(4):426-428.
    [16].钟述酞,董晖,张宝泉,等.自身免疫性甲状腺疾病患者淋巴细胞亚群和自身抗体的检测及其临床意义[J].天津医药,1994,22(7):391.
    [17]南京中医药大学编着.中药大辞典(M].上海:上海科学技术出版社,2006,3459-3465
    [18]李瑞琳,舒达夫.雷公藤的研究与临床应用[M].北京:中国科学技术出版社,1989,3-5
    [19]赵承暇,梅斌夫.中国雷公藤之研究[[J].中国生理学杂志,1936,10:529-534
    [20]吴大刚.昆明山海棠生物碱的鉴定[J].云南植物研究,1986,8(3):545-554
    [21]林绥,李援朝,等.雷公藤倍半菇生物碱的研究(Ⅳ)[J].植物学报,2001,43(6):647-69
    [22]何直升,洪山海.新生物碱雷公藤碱戊的结构[J].化学学报,1985,43(6)593-596
    [23]何直升,李亚,方圣鼎,洪山海.雷公藤碱乙、碱庚和碱己的结构[[J].化学学报,1987,45,510-513
    [24]Beroza M. Alkaloids from Triptcrygium wi 晌 rdii Hook.Isolation and Structure of Wilforzine[J].MORTONBEROZA,1953,75,2136-2138
    [24]邓福孝,夏志林,等.雷藤内酷四醇和雷公藤精碱的结构[J].植物学报,1992,34(8):618-621
    [25]Horiuch M, Murakami C, Fukamiya N, Yu D et al. Tripfordines A-C, Sesquiterpene Pyridine Alkaloids from Tripterygium wilfordii,and Structure Anti-HIV Activity Relationships of TripterygiumAlkaloids[J]. J.Nat.Prod.2006,69:1271-1274
    [26]Duan HQ, Yoshihisa T, et al. Immunosuppressive Sesquiterpene Alkaloids from Tripterygium wilfordii[J]. J.Nat.Prod,2001,64:582-587
    [27]龚苏晓,江纪武.雷公藤中新的倍半菇类生物碱和二菇类[[J].国外医学中医中药分册.2000,22(6):330-331
    [28]Li Y, George M, et al. Isowilfordine:An alkaloid from Tripterygium wilfordii Strunza[J]. Phytochemistry. 1991,30(2):719-721
    [29]Duan HQ, Kawazoe K, Yoshihisa T. Sesquiterpene alkaloids from Tripterygium hypoglaucum[J]. Phytochemistry.1997,45(3):617-621
    [30]Duan HQ, Takaishi Y. Sesquiterpene evoninate alkaloids from Tripterygium hypoglaucum[J]. Rhytochemistry.1999,52(8):1735-1738
    [31]Cheng CQ, Liu J k, Wu DG. An alkaloid from Tripterygium forresti.Phytochemistry[J]. 1992.31(12):4391-4392
    [1]白耀.甲状腺病学[M].北京:科学技术文献出版社,145-161.
    [2]Leslie J. Hashimoto's thyroiditis:A disease of autoimmunity. The thyroid and its disease [M].5 th edition1984:497-546.
    [3]Buchanan W Wet al. Association of thyrotoxicosis and autoimmune thyroiditis.Brit Med J,1961,5229(3):843.
    [4].张均田.现代药理实验方法[M].北京:北京医科大学中国协和医科大学联合出版社,1999:680-688.
    [5].朱立平,陈学清.免疫学常用实验方法[M].北京:人民军医出版社,2000.26-28.
    [1]Tanaka S,IsodaF,IshiharaYet al.T lymphopenia in relation to body mass index and TNF-a in humanobesity: adequate weight reduction can be corrective[J]. Clin Endoerino,2001,54(3):347.
    [2]陆福履。王胜军。许化溪.等,地塞米松治疗小鼠实验性自身免疫性甲状腺炎的研究[J].上海免疫学杂志。1998018(1):41.
    [3]Schwartz R. et al.Drug-induced immunological tolerance. Nature,1959,183:1682
    [4]Schwartz R, et al.The effects of 6-mercaptopurine on homograft reactions. J. Clin. Invest 196039:952
    [5]Davids S J. et al。The nature of molecular recognition by T cells. Nat Immunol,2003,4:217 [6]Gonzalez S,et al.Comparison of and isolated T cells afterinterferon-and interleukin-4 production by peripheral blood mononuclear cellsactivation with polyclonal T cell activators. J. Clin. Lab. Anal 1994.8:277
    [7]Pulendran B.Modulation TH 1/TH2 responses with microbes dendritic cells and pathogen recognition receptors. Immunol Res.2004.29:187
    [8]Estienne V, Duthoit C, Costanzo VD, et al.M ulticenter study on TGPO autoantibody prevalence in various thyroid and non thyroid diseases; relationships with thyroglobulin
    [9]Sridama V, et al. J Clin Endoerjnol etah,1982,54(2):316.
    [10]Wall JR, et al. J Clin Endocrinol Metab,1983,56(1):164.
    [11]Misaki T. et al. Acta EndocrInol,1984,105(2):200.
    [12]Ishikawa N, et al J Clin Endocrinol Metab,1987,85 (1):17.
    [13]Uekly. et al.J Clin Endocrinol Metab,1987,65(5):922.
    [141毕爱华.医学免疫学[M].北京:人民军医出版社,1997:7-15.
    [15]朱立平,陈学清.免疫学常用实验方法[M].北京:人民军医出版社,2000.26-28
    [16]Sloan-Lancaster J, Allen PM. Altered peptide ligand-induced partial T cell activation:molecular mechanisms and role in T cell biology[J]. Ann Rev Immunol,1996,14:1-27.
    [17]张剑宇.彭岚,刘定华.雷公藤对重症肌无力外周血T淋巴细胞亚群的影响.中国医药导报,2008,5(6):80-81
    [18]严士海,朱萱萱,孟达理.麻黄多糖对EAT小鼠外周血淋巴细胞亚群的影响.中华中医药学刊.2008,26(5):1069-1071
    [19].朱立平,陈学清.免疫学常用实验方法[M].北京:人民军医出版社,2000.26-28.
    [20].罗敏.分子内分泌学(基础与临床)[M].北京:人民军医出版社.2003.197-198.
    [21].张志远,郑武飞.Graves病和桥本氏甲状腺炎患者的T淋巴细胞亚群异常[J].国外医学·内分泌学分册,1984,9(3):134.
    [22].王云峰,魏枫.桥本甲状腺炎治疗前后淋巴细胞亚群及细胞学的变化[J].内蒙古医学杂志,2007,39(4):426-428.
    [23].钟述酞,董晖,张宝泉,等.自身免疫性甲状腺疾病患者淋巴细胞亚群和自身抗体的检测及其临床意义[J]天津医药,1994,22(7):391.
    [1]Hanabushi S, Koyangy M. Kauasaki A, et al. Fas and its ligand in a general mechanism of T-cell mediated cytotoxicity[J].PNAS LSA,1994,19:493.
    [2]Nagata S, Golstein P. The Fas death factor[J].Science,1995; 267:1449.
    [3]Arscott PL, Knapp J, Rymaszewski M, et al.Fas (APO-1CD95)-mediated apoptosis in thyroid cell is regulated by a labile protein inhibitor[J].Endocrinology,1997,138:5019
    [4]Motyka B, Korbutt G, et al·Mannose 6-phosphate/insulin-link groth factor lireceptor is a death receptor for gmnzyme B during cytotoxic T cell-induced apoptosis [J]. Cell,2000,103:491-500
    [5]Giordano C. Stassi G, De Mafia R, et al.Potential involvement of Fas and its ligand in the pathogcnesis of Hashimoto'sthyroiditis in MRL-lpr/Ipr mice[J].science,1997,275:960-963
    [6]张均田.现代药理实验方法[M].北京:北京医科大学中国协和医科大学联合出版社,1999:680-688.
    [7]朱立平,陈学清.免疫学常用实验方法[M].北京:人民军医出版社,2000.26-28.
    [8]张雅萍,姬秋如,张万会,等.桥本甲状腺炎中Fas和Fas-L的表达[J].第四军医大学学报,2000;21(2):223-225.
    [9]高福智,陈晓梅,赵文革,等.Fas系统介导的细胞凋亡与大鼠白体免疫性甲状腺炎的研究[J].内分泌外科杂志,2008,3(2):76-78.
    [1]田英娟.细胞凋亡与自身免疫性甲状腺疾病[J].齐鲁医学杂志,2005,20(6):557-558.
    [2]林来祥,叶振坤.碘对大鼠甲状腺细胞凋亡及Bax, Bcl-2基因mRNA表达的影响[J].中国地方病学杂志,2005,24(3)245-247.
    [3]SRINIVASULA S M, SALEH A, AHMAD M, et al. Isola-tion and assay of caspases[J].Methods Gell Biol,2001,66:1-27.
    [4]TANG R, LIU H, WANG T, et al. Mechanisms of seleniuminhibition of cell apoptosis induced by oxysterols in ratvascular
    [5]smoothmuscle cells[J].Arch Biochem Biophys,2005,441(1):16-24.
    [6]黄英如,蒋电明.雷公藤促细胞凋亡的分子机理概述.实用中医药杂志,2007,23(12):809-811.49
    [7]Bretz J D, Baker J D. Apoptosis and autoimmune thyroid disease:following a TRAIL to thyroid destruction[J].Glin Dndocrinol,2001,55:1-11.
    [8]Ehrlich S, Infante-Duarte C, Seeger B, et al. Regulation of soluble and surface-bound TRAIL in human T cells, B cells, and monocytes[J].cytokine,2003,24(6):244 253.
    [9]Daniels R A, Turley H, Kimberley F C, et al. Expression of TRAIL and TRAIL receptors in normal and malignant tissues[J].Gell Res,2005,15(6):430-438.
    [10]Wang Q, Wang X, Hernandez A, et al. Regulation of TRAIL expression by the phosphatidylinositol 13-kinase/A kt/GSK-3 pathway in human colon cancer cells[J].J Biol Chem,2002,277(39):36602-36610.
    [11]Srinivasula S M, Saleh A, Ahmad M, et al. Isolation and assay of caspases[J].Methods Gell Biol,2001,66: 1-27.
    [12]Xu S Q, EI-Deiry W S. P21(WAF1/ CIP1) inhibits initiator caspase cleavage by TRAIL death receptor DR4[J].Biophys Res Commnn,2000,269(1):1791.
    [13]Hao C, Beguinot F, Condorelli G, et al. Induction and intracel- lular regulation of tumor necrosis factorrelated apoptosis indu-cing ligand(TRAIL) mediated apoptosis in human malignant glioma cells[J].Gancer Res,2001,61(3):1162.
    [14]Kim H S, Chang I, Kim J Y, et al. Caspase-mediated p65 cleav- age promotes TRAIL-induced apoptosis[J].Cancer Res,2005,65(14):6111-6119.

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