益气活血解毒法对氧化低密度脂蛋白诱导人脐静脉内皮细胞粘附作用的影响
|
摘要
下肢动脉硬化闭塞症(ASO)是动脉粥样硬化物质不断扩大和继发血栓形成导致的下肢动脉管腔的狭窄、闭塞性病变。患肢表现为发冷、麻木、疼痛、间歇性跛行、动脉搏动消失、营养障碍、趾端、足部甚至小腿发生溃疡或者坏疽。患者生活质量严重下降,甚至失去肢体,严重者甚至危及生命对社会也是很大的负担。随着生活水平的提高、饮食结构的改变以及人均寿命的延长,ASO的发病率显示出上升趋势,成为严重危害人民健康的一种老年常见病和多发病,同时也是当前众多学者研究的重要科题。
近年来多数学者支持“内皮损伤反应学说”。认为本病各种主要危险因素最终都损伤动脉内膜,动脉硬化的始动环节是血管内皮损伤及内皮功能障碍,氧化低密度脂蛋白(OX-LDL)和炎性反应在引起内皮功能障碍和启动动脉粥样硬化(AS)中发挥重要作用。
本研究试图探索益气、活血、解毒法中药对OX-LDL损伤的人脐静脉内皮细胞(HUVEC)时的粘附分子的基因表达、转录调控通路及与单核细胞粘附作用的机制,为中药制剂的联合应用治疗下肢动脉硬化闭塞症提供理论依据,并为中药干预下肢动脉硬化闭塞症的发病机理研究探索新途径和提供一种新的研究思路和方法。
(OX-LDL)诱导的HUVEC与单核细胞黏附率的影响研究
目的：探讨益气、活血、解毒法不同药物组合对单核细胞黏附率的干预作用。
方法：共分6组A、正常对照组B、OX-LDL损伤后的HUVEC C. OX-LDL损伤的HUVEC+益气、活血、解毒组D. OX-LDL损伤的HUVEC+益气、活血组E. OX-LDL损伤的HUVEC+活血、解毒组F. OX-LDL损伤的HUVEC+益气、解毒组。提取健康人外周血单核细胞与各组HUVEC黏附作用1h后,BCA蛋白定量法测定每组单核细胞黏附率。SPSS16.0统计软件包进行数据分析。
结果：(1) OX-LDL能显著增加人脐静脉内皮细胞与单核细胞黏附率(P<0.01)。(2)益气、活血、解毒三法不同药物组合后均能明显降低HUVEC与单核细胞黏附率(P<0.01)。(3)不同治法药物组合组间,单核细胞的粘附率也有显著差异：①益气活血解毒组单核细胞黏附率最低；②益气活血组黏附率较高,数值仅低于不加药的OX-LDL损伤的HUVEC组；③含有解毒治法组的单核细胞黏附率均偏低。
2、OX-LDL诱导的HUVEC的ICAM-1、VCAM-1、NF-κB p65的蛋白表达研究
目的：探讨益气、活血、解毒法不同药物组合对OX-LDL损伤后的HUVEC的ICAM-1、VCAM-1、NF-κB p65的蛋白表达表达的干预作用。
方法：共分10组A、正常对照组B、OX-LDL损伤后的HUVEC C. OX-LDL损伤的HUVEC+益气、活血、解毒组D. OX-LDL损伤的HUVEC+益气、活血组E. OX-LDL损伤的HUVEC+活血、解毒组F. OX-LDL损伤的HUVEC+益气、解毒组。蛋白质的SDS-聚丙烯酰胺凝胶电泳和免疫印记法检测中药干预后OX-LDL诱导的HUVEC的ICAM-1、VCAM-1和NF-κB p65的蛋白表达,SPSS16.0统计软件包进行数据分析。
结果：其中VCAM-1在正常HUVEC组几乎不表达；NF-κB p65蛋白在有单核细胞粘附作用的4、8、9组均有显著表达。
3、OX-LDL诱导的HUVEC的ICAM-1、VCAM-1、NF-κB p65的mRNA表达研究
目的：探讨益气、活血、解毒法不同药物组合对OX-LDL损伤后的HUVEC的ICAM-1、VCAM-1、NF-κB p65的mRNA表达的干预作用。
方法：共分10组A、正常对照组B、OX-LDL损伤后的HUVEC C. OX-LDL损伤的HUVEC+益气、活血、解毒组D. OX-LDL损伤的HUVEC+益气、活血组E. OX-LDL损伤的HUVEC+活血、解毒组F. OX-LDL损伤的HUVEC+益气、解毒组。荧光实时定量PCR法检测中药干预后OX-LDL诱导的HUVEC的ICAM-1、VCAM-1和NF-κBp65的mRNA表达。采用SPSS 16.0统计软件,计量资料用均数士标准差表示,多组间计量资料的比较采用方差分析,组间比较用LSD法,P<0.01统计学上认为具有显著性差异。
结果：益气、活血、解毒法可明显降低ICAM-1和VCAM-1的mRNA和蛋白的表达水平,与ox-LDL组比较差异有统计学意义(P<0.01)。
总结论：益气、活血、解毒法能通过下调内皮细胞表面黏附分子的表达；推测是通过抑制NF-κβ,抑制单核-血管内皮细胞黏附,从而发挥对血管内皮细胞的保护作用,有利于减少或抑制动脉粥样硬化的形成。
Arteriosclerosis obliterans (ASO) is atherosclerotic material expanding and secondary thrombosis of lower extremity due to the narrow arteries, occlusive disease. Limb showed chills, numbness, pain, intermittent claudication, arterial pulse disappeared, Nutrition disorders, toe, foot or leg ulcers or gangrene occur. Serious decline in quality of life of patients, and even loss of limbs, serious and even life-threatening but also a great burden on society. With the improvement of living standards, changes in diet, and longevity, ASO incidence rates showed an upward trend, as serious harm to people's health, a common disease, and frequently-occurring, but also the numerous scholars of the important subjects question.
In recent years, most scholars support the "theory of endothelial injury in response." That the major risk factors for this disease eventually intimal injury, atherosclerosis, is part of the initiating endothelial injury and endothelial dysfunction, oxidation of low density lipoprotein (OX-LDL) in causing endothelial dysfunction and atherosclerosis starts sclerosis (AS) play an important role.
This study attempts to explore the qi, blood, detoxification method of Chinese medicine OX-LDL on human umbilical vein injury in endothelial cells (HUVEC) adhesion molecule during gene expression, transcriptional regulatory pathway and the role of monocyte adhesion mechanism for Combination therapy of Chinese medicine preparation arteriosclerosis obliterans of lower limbs to provide a theoretical basis for Chinese medicine treatment of lower extremity arterial occlusive disease pathogenesis and provide new ways of exploring a new research ideas and methods.
1、OX-LDL-induced HUVEC and monocyte adhesion rates
Objective:Qi, activating blood circulation, detoxification method combination of different drugs on monocyte adhesion in rats.
Methods:divided into 6 groups A, normal control group B, OX-LDL after injury HUVEC C. OX-LDL injury HUVEC+Qi, activating blood circulation, detoxification group D. OX-LDL injury in HUVEC+qi, blood group E. OX-LDL injury in HUVEC+blood, detoxification group F. OX-LDL injury in HUVEC+Qi, detoxification group. Extraction of human peripheral blood mononuclear cells and HUVEC adhesion in each group after 1h, BCA protein determination of each rate of monocyte adhesion. SPSS 16.0 statistical package for data analysis. Results:(1) OX-LDL significantly increased the human umbilical vein endothelial cells and mononuclear cell adhesion rate (P<0.01). (2) Qi, activating blood circulation, detoxify the triple combination of different drugs could reduce the HUVEC and mononuclear cell adhesion rate (P <0.01). (3) of different therapies and drug combinations group, mononuclear cell adhesion rates were significantly different:①Yiqihuoxue detoxification group the lowest rate of monocyte adhesion;②Yiqihuoxue the adhesion rate was higher value than not only Dosing of OX-LDL HUVEC injury group;③with detoxification therapies group low rate of monocyte adhesion.
2, OX-LDL-induced HUVEC of ICAM-1, VCAM-1, NF-κB p65 protein expression
Objective:Qi, activating blood circulation, detoxification method of different drug combinations on the OX-LDL after injury HUVEC of ICAM-1, VCAM-1, NF-κB p65 protein expression in the intervention.
Methods:divided into 10 groups A, normal control group B, OX-LDL after injury HUVEC C. OX-LDL injury HUVEC+Qi, activating blood circulation, detoxification group D. OX-LDL injury in HUVEC+qi, blood group E. OX-LDL injury in HUVEC+blood, detoxification group F. OX-LDL injury in HUVEC+Qi, detoxification group. Protein SDS-polyacrylamide gel electrophoresis and Western blot assay after the intervention of Chinese medicine OX-LDL-induced HUVEC of ICAM-1, VCAM-1 and NF-κB p65 protein expression, SPSS 16.0 statistical package for data analysis.
3, OX-LDL-induced HUVEC of ICAM-1, VCAM-1, NF-κB p65 in mRNA expression Objective:Qi, activating blood circulation, detoxification method of different drug combinations on the OX-LDL after injury HUVEC of ICAM-1, VCAM-1, NF-κB p65 in mRNA expression in rats.
Methods:divided into 10 groups A, normal control group B, OX-LDL after injury HUVEC C. OX-LDL injury HUVEC+Qi, activating blood circulation, detoxification group D. OX-LDL injury in HUVEC+qi, blood group E. OX-LDL injury in HUVEC+blood, detoxification group F. OX-LDL injury in HUVEC+Qi, detoxification group. Real-time fluorescence quantitative PCR, after the Chinese intervention in OX-LDL-induced HUVEC of ICAM-1, VCAM-1 and NF-κB p65 of the mRNA. Using SPSS 16.0 statistical software measurement data with a mean±standard deviation between the measurement of multiple analysis of variance was used to compare data among the groups using LSD method, P＜0.05 considered statistically significant difference.
Results:Qi, activating blood circulation, detoxification method can significantly reduce ICAM-1 and VCAM-1 in mRNA and protein expression levels, and o x-LDL group difference was significant (P<0.05, P<0.01).
General Conclusion:Qi, activating blood circulation, detoxification method through the reduction in endothelial cell adhesion molecules; presumably by inhibiting NF-κβ,inhibition of monocyte-endothelial cell adhesion to vascular endothelial cells play a protective role in helping reduce or inhibit the formation of atherosclerosis.
近年来多数学者支持“内皮损伤反应学说”。认为本病各种主要危险因素最终都损伤动脉内膜,动脉硬化的始动环节是血管内皮损伤及内皮功能障碍,氧化低密度脂蛋白(OX-LDL)和炎性反应在引起内皮功能障碍和启动动脉粥样硬化(AS)中发挥重要作用。
本研究试图探索益气、活血、解毒法中药对OX-LDL损伤的人脐静脉内皮细胞(HUVEC)时的粘附分子的基因表达、转录调控通路及与单核细胞粘附作用的机制,为中药制剂的联合应用治疗下肢动脉硬化闭塞症提供理论依据,并为中药干预下肢动脉硬化闭塞症的发病机理研究探索新途径和提供一种新的研究思路和方法。
(OX-LDL)诱导的HUVEC与单核细胞黏附率的影响研究
目的：探讨益气、活血、解毒法不同药物组合对单核细胞黏附率的干预作用。
方法：共分6组A、正常对照组B、OX-LDL损伤后的HUVEC C. OX-LDL损伤的HUVEC+益气、活血、解毒组D. OX-LDL损伤的HUVEC+益气、活血组E. OX-LDL损伤的HUVEC+活血、解毒组F. OX-LDL损伤的HUVEC+益气、解毒组。提取健康人外周血单核细胞与各组HUVEC黏附作用1h后,BCA蛋白定量法测定每组单核细胞黏附率。SPSS16.0统计软件包进行数据分析。
结果：(1) OX-LDL能显著增加人脐静脉内皮细胞与单核细胞黏附率(P<0.01)。(2)益气、活血、解毒三法不同药物组合后均能明显降低HUVEC与单核细胞黏附率(P<0.01)。(3)不同治法药物组合组间,单核细胞的粘附率也有显著差异：①益气活血解毒组单核细胞黏附率最低；②益气活血组黏附率较高,数值仅低于不加药的OX-LDL损伤的HUVEC组；③含有解毒治法组的单核细胞黏附率均偏低。
2、OX-LDL诱导的HUVEC的ICAM-1、VCAM-1、NF-κB p65的蛋白表达研究
目的：探讨益气、活血、解毒法不同药物组合对OX-LDL损伤后的HUVEC的ICAM-1、VCAM-1、NF-κB p65的蛋白表达表达的干预作用。
方法：共分10组A、正常对照组B、OX-LDL损伤后的HUVEC C. OX-LDL损伤的HUVEC+益气、活血、解毒组D. OX-LDL损伤的HUVEC+益气、活血组E. OX-LDL损伤的HUVEC+活血、解毒组F. OX-LDL损伤的HUVEC+益气、解毒组。蛋白质的SDS-聚丙烯酰胺凝胶电泳和免疫印记法检测中药干预后OX-LDL诱导的HUVEC的ICAM-1、VCAM-1和NF-κB p65的蛋白表达,SPSS16.0统计软件包进行数据分析。
结果：其中VCAM-1在正常HUVEC组几乎不表达；NF-κB p65蛋白在有单核细胞粘附作用的4、8、9组均有显著表达。
3、OX-LDL诱导的HUVEC的ICAM-1、VCAM-1、NF-κB p65的mRNA表达研究
目的：探讨益气、活血、解毒法不同药物组合对OX-LDL损伤后的HUVEC的ICAM-1、VCAM-1、NF-κB p65的mRNA表达的干预作用。
方法：共分10组A、正常对照组B、OX-LDL损伤后的HUVEC C. OX-LDL损伤的HUVEC+益气、活血、解毒组D. OX-LDL损伤的HUVEC+益气、活血组E. OX-LDL损伤的HUVEC+活血、解毒组F. OX-LDL损伤的HUVEC+益气、解毒组。荧光实时定量PCR法检测中药干预后OX-LDL诱导的HUVEC的ICAM-1、VCAM-1和NF-κBp65的mRNA表达。采用SPSS 16.0统计软件,计量资料用均数士标准差表示,多组间计量资料的比较采用方差分析,组间比较用LSD法,P<0.01统计学上认为具有显著性差异。
结果：益气、活血、解毒法可明显降低ICAM-1和VCAM-1的mRNA和蛋白的表达水平,与ox-LDL组比较差异有统计学意义(P<0.01)。
总结论：益气、活血、解毒法能通过下调内皮细胞表面黏附分子的表达；推测是通过抑制NF-κβ,抑制单核-血管内皮细胞黏附,从而发挥对血管内皮细胞的保护作用,有利于减少或抑制动脉粥样硬化的形成。
Arteriosclerosis obliterans (ASO) is atherosclerotic material expanding and secondary thrombosis of lower extremity due to the narrow arteries, occlusive disease. Limb showed chills, numbness, pain, intermittent claudication, arterial pulse disappeared, Nutrition disorders, toe, foot or leg ulcers or gangrene occur. Serious decline in quality of life of patients, and even loss of limbs, serious and even life-threatening but also a great burden on society. With the improvement of living standards, changes in diet, and longevity, ASO incidence rates showed an upward trend, as serious harm to people's health, a common disease, and frequently-occurring, but also the numerous scholars of the important subjects question.
In recent years, most scholars support the "theory of endothelial injury in response." That the major risk factors for this disease eventually intimal injury, atherosclerosis, is part of the initiating endothelial injury and endothelial dysfunction, oxidation of low density lipoprotein (OX-LDL) in causing endothelial dysfunction and atherosclerosis starts sclerosis (AS) play an important role.
This study attempts to explore the qi, blood, detoxification method of Chinese medicine OX-LDL on human umbilical vein injury in endothelial cells (HUVEC) adhesion molecule during gene expression, transcriptional regulatory pathway and the role of monocyte adhesion mechanism for Combination therapy of Chinese medicine preparation arteriosclerosis obliterans of lower limbs to provide a theoretical basis for Chinese medicine treatment of lower extremity arterial occlusive disease pathogenesis and provide new ways of exploring a new research ideas and methods.
1、OX-LDL-induced HUVEC and monocyte adhesion rates
Objective:Qi, activating blood circulation, detoxification method combination of different drugs on monocyte adhesion in rats.
Methods:divided into 6 groups A, normal control group B, OX-LDL after injury HUVEC C. OX-LDL injury HUVEC+Qi, activating blood circulation, detoxification group D. OX-LDL injury in HUVEC+qi, blood group E. OX-LDL injury in HUVEC+blood, detoxification group F. OX-LDL injury in HUVEC+Qi, detoxification group. Extraction of human peripheral blood mononuclear cells and HUVEC adhesion in each group after 1h, BCA protein determination of each rate of monocyte adhesion. SPSS 16.0 statistical package for data analysis. Results:(1) OX-LDL significantly increased the human umbilical vein endothelial cells and mononuclear cell adhesion rate (P<0.01). (2) Qi, activating blood circulation, detoxify the triple combination of different drugs could reduce the HUVEC and mononuclear cell adhesion rate (P <0.01). (3) of different therapies and drug combinations group, mononuclear cell adhesion rates were significantly different:①Yiqihuoxue detoxification group the lowest rate of monocyte adhesion;②Yiqihuoxue the adhesion rate was higher value than not only Dosing of OX-LDL HUVEC injury group;③with detoxification therapies group low rate of monocyte adhesion.
2, OX-LDL-induced HUVEC of ICAM-1, VCAM-1, NF-κB p65 protein expression
Objective:Qi, activating blood circulation, detoxification method of different drug combinations on the OX-LDL after injury HUVEC of ICAM-1, VCAM-1, NF-κB p65 protein expression in the intervention.
Methods:divided into 10 groups A, normal control group B, OX-LDL after injury HUVEC C. OX-LDL injury HUVEC+Qi, activating blood circulation, detoxification group D. OX-LDL injury in HUVEC+qi, blood group E. OX-LDL injury in HUVEC+blood, detoxification group F. OX-LDL injury in HUVEC+Qi, detoxification group. Protein SDS-polyacrylamide gel electrophoresis and Western blot assay after the intervention of Chinese medicine OX-LDL-induced HUVEC of ICAM-1, VCAM-1 and NF-κB p65 protein expression, SPSS 16.0 statistical package for data analysis.
3, OX-LDL-induced HUVEC of ICAM-1, VCAM-1, NF-κB p65 in mRNA expression Objective:Qi, activating blood circulation, detoxification method of different drug combinations on the OX-LDL after injury HUVEC of ICAM-1, VCAM-1, NF-κB p65 in mRNA expression in rats.
Methods:divided into 10 groups A, normal control group B, OX-LDL after injury HUVEC C. OX-LDL injury HUVEC+Qi, activating blood circulation, detoxification group D. OX-LDL injury in HUVEC+qi, blood group E. OX-LDL injury in HUVEC+blood, detoxification group F. OX-LDL injury in HUVEC+Qi, detoxification group. Real-time fluorescence quantitative PCR, after the Chinese intervention in OX-LDL-induced HUVEC of ICAM-1, VCAM-1 and NF-κB p65 of the mRNA. Using SPSS 16.0 statistical software measurement data with a mean±standard deviation between the measurement of multiple analysis of variance was used to compare data among the groups using LSD method, P＜0.05 considered statistically significant difference.
Results:Qi, activating blood circulation, detoxification method can significantly reduce ICAM-1 and VCAM-1 in mRNA and protein expression levels, and o x-LDL group difference was significant (P<0.05, P<0.01).
General Conclusion:Qi, activating blood circulation, detoxification method through the reduction in endothelial cell adhesion molecules; presumably by inhibiting NF-κβ,inhibition of monocyte-endothelial cell adhesion to vascular endothelial cells play a protective role in helping reduce or inhibit the formation of atherosclerosis.
引文
[1]王玉琦,叶建荣.血管外科治疗学[M].上海：上海科学技术出版社2003：136
[2]李小鹰,王洁,何耀,范利.周围动脉硬化闭塞症在老年血脂异常人群中的现患率调查[J].中华老年心脑血管病杂志2005,2.(7)：3-4.
[3]Hansson GK. Inflammation and atherosclerosis, and coronary artery disease [J]. N Engl J Med,2005,352:1685-1695
[4]Wic, Knoflach M, Xu Q. Autoimmune and inflammatory mechanisms in atherosclerosis [J]. Annu Rev Immunol,2004,22:361-403.
[5]李建华,郭志刚,吴平生,杨永红,赖文岩.血管内皮细胞中ABCA1的表达及其在动脉粥样硬化发生中的意义[J].第一军医大学学报,2004,24,(9)：980-983
[6]马丽,朱文云,李宏妹,邢海燕,金永娟.OX-LDL对内皮细胞粘附分子表达及粘附功能影响的研究[J].微循环学杂志,2000.3(10)：49
[7]危当恒,王贵学,黄华,刘录山,王佐,唐朝克.低密度脂蛋白对血管内皮细胞骨架及粘附能力的影响[J].医用生物学,2006,21,(6)：105-110
[8]林秋雄,余细勇,单志新,林曙光.氧化型低密度脂蛋白对血管内皮细胞ICAM-1 mRNA表达的影响[J].岭南心血管志,2003,9,(4)：282-284.
[9]Callow AD. Endothelial dysfunction in atherosclerosis [J]. Vascul Pharm acol,2002,38 (5):257-258.
[10]Golino P, Piscione F, Willerson JT, et al. Divergent effects of serotonin on coronary artery dimensions and blood flow in patients withcoronary atherosclerosis and control patients [J]. N Engl J Med,1991, 324 (10):641-648.
[11]Lerman A, Holmes DR J r, BellMR, et al. Endothelin in coronary endothelial dysfunction and early atherosclerosis in humans[J]. Circulation,1995,92 (9):2426-2431.
[12]Geisler T, Bhatt DL. The role of inflammation in atherothrombosis: current and future strategies of medical treatment [J]. Med SciMonit,2004, 10(12):RA308-316.
[13]Cybulsky M I, Iiyama K, Li H, et al. A major role for VCAM-1, but not ICAM-1, in early atherosclerosis [J]. J Clin Invest,2001,107(10): 1255-1262.
[14]Boring L, Gosling J, Cleary M, et al. Decreased lesion formation inCCR2-/-mice reveals a role for chemokines in the initiation of atherosclerosis [J]. Nature,1998,394 (6696):894-897.
[15]HermanMP, Sukhova GK, Libby P, et al. Exp ression of neutrophil collagenase (matrixmetalloproteinase28) in human atheroma:a novel collagenolytic pathway suggested. by transcriptionalp rofiling[J]. Circulation,2001,104 (16):1899-1904.
[16]Libby P, Geng YJ, AikawaM, et al. Macrophages and atherosclerotic plaque stability[J]. CurrOpin L ipidol,1996,7 (5):330-335.
[17]Chamorro A. Role of inflammation in stroke and atherothrombosis [J]. Cerebrovasc D is,2004,17 (Supp 13):125.
[18]Ridker PM, StampferMJ, Rifai N. Novel risk factors for systemic atherosclerosis:a comparison of C2reactive p rotein, fibrinogen, homocysteine, lipoprotein (a), and standard cholesterol screening as predictors of peripheral arterial disease[J]. JAMA,2001,285 (19):2481-2485.
[19]Ridker PM, Hennekens CH, Buring JE, et al. C2reactive protein and othermarkers of inflammation in the prediction of cardiovascular disease in women[J]. N Engl J Med,2000,342 (12):836-843
[20]KITAGAWAK, MATSUMOTOM, MABUCHI T, et al. Deficiency of intercellular adhesion molecule-1 attenuates microcirculatory disturbance and infarction sizein focal cerebral ischemia [J]. Cereb Blood Flow Betab, 1998,18(12):336-345
[21]STANIMIROVIC DB, WONG J, SHAPIRO A, et al. Increase in surface expression of ICAM-1, VCAM-1 and E-selectin in human cerebromicrovascular endothelial cells subjected to ischemia-like insults [J]. Acta Neurochir Suppl,1997,70:12-16
[22]Brand K, Page S,Rogler G et al. Activiated transcription factor nuclear Factor-kappaB is present in the atherosclerotic lesion. J Clin Invest,1996; 97(7):1715-1722
[23]Baeuerle PA. The inducible transcription activator NF-kappaB: Regulation by distinct protein subunits. Biochim Biophys Act,1991; 1072 (1):63-80
[24]Dagia NM, Harii N, Meli AE, et al. Phenyl methimazole inhibits TNF-alpha induced VCAM-1 expression in an IFN regulatory factor-1-dependent manner and reduces monocytic cell adhesion to endothelial cells J Immunol 2004,173(3):2041-2049
[25]Lin WN, Luo SF, Lee CW, et al. Involvement of MAPKs and NF-kappaB in LPS-induced VCAM-1 expression inhuman tracheal smooth muscle cells. Cell Signal 2007; 19
[26]Chen YH, Lin SJ, Chen JW, et al. Magnolol attenuates VCAM-lexpression in vitro in TNF-alpha-treated human aortic endothelial cells and in vivo in the aorta of choles terol-fed rabbits. Br J Pharmacol 2002; 135(1):37-47
[27]Hall G, Hasday JD, Rogers TB. Regulating the regulator:NF-kappaB signaling in heart. J Mol Cell Cardiol 2006; 41(4):580-591
[28]Zhong C, Zhou Y, Liu H. Nuclear factor kappaB and anesthetic Preconditioning during myocardial ischemia reperfusion. Anesthesiology2004; 100(3):540-546
[29]Tsurumi Y, Takeshita S,Chen D, et al. Direct intramuscular gene transfer of naked DNA encoding vascular endothelial growth factor augments ollateral development and lissueperfusion [J]. circulation,1996,94 (12):3281
[30]尚德俊,王嘉桔,王书桂.中西医结合周围血管疾病学.海口：南海出社,1995：119—223.
[31]郝群,李大金,朱影,等.补肾宁心方对去势高脂血症家兔主动脉血管细胞粘附因子1表达的调节[J].中国动脉硬化杂志,2004,12(3)：301-304.
[32]郝群,李大全,朱影,等.补肾宁心方对单核-内皮细胞在动脉粥样硬化中相互作用的影响[J].中国老年学杂志,2004,24(4)：337-339.
[33]任钧国,邱全瑛,郝钰,等.清解宁对白细胞-血管内皮细胞粘附的影响[J].中国免疫学杂志,2003,19(4)：618.
[34]周沐科,何俐,吴波,等,大川芎丸对血管内皮细胞中血管内皮生长因子分泌水平的影响[J].中国临床康复,2004,8(19)：3842-3843.
[35]喻嵘,陈大舜,梅志刚,等.左归双降方对葡萄糖胰岛素低密度脂蛋白诱导损伤的血管内皮细胞ICAM-1 tPA PAI的影响[J].中医药学刊,2005,23(1)：61-63.
[36]赵建宏,林琳,曹卉,等.益气活血中药防治大鼠血管内皮细胞损伤的实验研究[J].微循环学杂志,2001,11(2)：36-38.
[37]任勇才.中药制剂治疗血脂异常概况.广西中医学院学报,2004,7(4)64～66.
[38]严瑾,沃兴德,范春雷,等.山楂叶总黄酮对PPARγ-PPRE信号调控系统的影响.中国药学杂志,2005,40(8)：625～628.
[39]任钧国,邱全瑛,郝钰,等.清解宁对白细胞-血管内皮细胞粘附的影响[J].中国免疫学杂志,2003,19(4)：618.
[40]周沐科,何俐,吴波,等,大川芎丸对血管内皮细胞中血管内皮生长因子分泌水平的影响[J].中国临床康复,2004,8(19)：3842-3843.
[41]喻嵘,陈大舜,梅志刚,等.左归双降方对葡萄糖胰岛素低密度脂蛋白诱导损伤的血管内皮细胞ICAM-1 tPA PAI的影响[J].中医药学刊,2005,23(1)：61
[42]赵建宏,林琳,曹卉,等.益气活血中药防治大鼠血管内皮细胞损伤的实验研究[J].微循环学杂志,2001,11(2)：36-38.
[43]王保华,欧阳静萍,魏蕾,等.当归及阿魏酸钠对内皮细胞中TGF β1及bFGF表达的影响[J].辽宁中医杂志,2001,28(1)：45-46.
[44]何晓琳,刘志.青蒿琥酯对脂多糖致血管内皮细胞活化及损伤的保护作用[J].中国中西医结合杂志,2004,24(12)：1110-1113.
[45]郝钰,邱全瑛,吴珺,等.小檗碱对淋巴细胞与血管内皮细胞粘附因子的影响[J].中国免疫学杂志,1999,15(11)：523-525.
[46]郝钰,邱全瑛,吴珺,等.黄芪多糖促进中性粒细胞与血管内皮细胞粘附及相关粘附分子表达[J].中国中西医结合志,2004,24(5)：427-430.
[47]李敏杰,刘永,马琳,等.葛根素对内皮细胞增殖及粘附分子表达的影响[J].陕西中医,2002,23(2)：78-79.
[48]朱雄翔,汤朝武,陈璧.烧伤早期及丹参对中性粒细胞化学发光的影响[J].第四军医大学学报,1999,20(10)：924.
[49]Chen Y H, Lin S J,Ku H H,et al. Salvianolic acid B attenuates VCAM-1 and ICAM-1 expression in TNF alpha-treated human aortic endothelial cells [J]. Cell Biochem,2001,82(3):512.
[50]刘春华,钱冠清,刘会齐,等.银杏叶提取物抑制轻度修饰低密度脂蛋白诱导的血管内皮细胞与单核细胞粘附的实验研究[J].中国中西医结合杂志,2000,20(12)：917.
[51]贺兰萍,高建英,昌艳艳,等.穿心莲对兔胸主动脉内膜损伤后血管内皮细胞中PDGF-B蛋白的表达影响[J].中国老年杂志,2005,25(2)：182-183.
[52]接传红,高健生.中药密蒙花抗血管内皮细胞增生作用的研究[J].眼科,2004.13(6)：348-350.
[53]王云开,苏海,程晓曙.茶色素对培养猪离体主动脉内皮细胞功能影响的实验研究[J].高血压杂志,1999,1(7)：56.
[54]吴德芹,张旭.麦冬药血清对静脉内皮细胞直管调解物质的影响[J].中医药学报,2004,32(2)：40-44.
[55]李民,张旭,朱平,等.麦冬、生地药血清对直管内皮细胞增殖的影响[J].国医论坛,2001,16(5)：83-85.
[56]吴勇,等.黄芪多糖对糖尿病大鼠血管内皮细胞的影响[J].辽宁中医杂志,2002,29, (1)：22-23
[57]李萍等.黄芪多糖对细胞增殖及血管内皮细胞与白细胞粘附作用的影响[J].中国病理生理杂志,2004,20(9)：1677-1680
[58]晏庆德,张学颖.补阳还五汤片剂治疗早期动脉硬化性闭塞症临床研究[J].山杂志东中医,2005.3：140-143
[59]柳国斌等。脉健方治疗肢体动脉粥样硬化闭塞症的临床研究[J].河北中医,2002.1(24)：5-7
[60]刘健齐.清会.通脉冲剂治疗动脉粥样硬化闭塞症的实验研究[J].天津医药,2003.5.(31)：304-306
[61]蒋洪庆.股动脉注射脉络宁等药物治疗下肢动脉硬化性闭塞症[J].中国临床医生,2002.12.
[62]吴文元.川芎嗪治疗周围动脉粥样硬化闭塞症疗效观察[J]实用中医药杂志,2002.8.(18)：5
[63]郝群,李大全,朱影,等.补肾宁心方对单核-内皮细胞在动脉粥样硬化中相互作用的影响[J].中国老年学杂志,2004,24(4)：337-339.
[64]钱小奇.试论高脂血症的病因病机[J].天津中医,2002,19(6)：51.
[65]刘春玲,唐蜀华,孙云霞.芦黄颗粒对实验性动脉粥样硬化家兔C反应蛋白和白细胞介素-6水平的影响[J].中国中西医结合急救杂志,2005,12(6)：366-368.
[66]Vladimir R B, Lei Ding, Jeff R, et al. Cyclooxygenase-1 deficien2cy in bone marrow cells increases early atherosclerosisin apolipopro2tein E and low-density lipoprotein receptornullmice[J].Circulation,2006,113:108-117.
[67]Hansson GK. Inflammation and atherosclerosis, and coronary artery disease[J]. N Engl J Med,2005,352:1685-1695
[68]Wic, Knoflach M, Xu Q. Autoimmune and inflammatory mechanisms in atherosclerosis[J]. Annu Rev Immunol,2004,22:361-403
[71]吕志军,梁绪国.三七总皂苷对血管内皮细胞凋亡及凋亡调控基因的影响[J]1中西医结合心脑血管病杂志,2005,3(11)：975-977.
[72]闫彦芳,张壮,孙塑伦,等.三七总皂苷及其主要成分对血管内皮细胞缺氧损伤的保护作用[J]。中国实验方剂学杂志,2002,8(1)：34-37.
[73]曾桂凤,刘建勋,李澎,等.丹参三七不同配比对缺氧损伤人脐静脉内皮细胞的保护作用[J]精细化工,2006,23(2)：126-129。
[74]文川,徐浩,黄启福,等.活血中药对ApoE基因缺陷小鼠血脂及动脉粥样硬化斑块炎症反应的影响[J].中国中西医结合杂志,2005,25(4)：345-349.
[75]贾乘,张林,程嘉艺,等.三七抑制大鼠血栓形成实验研究[J]1中医药学刊,2001,19(2)：172-173.
[76]李家增,贺石林,王鸿利.血栓病学[M].北京：科学出版社,1998.
[77]王阶,许军,衷敬柏,等.三七总苷对高黏血症患者血小板活化分子表达和血小板聚集的影响[J].中国中西医结合杂志,2004,24(4)：312-316.
[78]谢飞,何恩平,张莉,等.黄芪药理研究进展[J]. 中国药理学通报,1994,15(2)：157-159.
[79]尹小川,刘健康,周序珑,等.三七总皂甙对培养的猪主动脉内皮细胞释放一氧化氮的影响[J].中国动脉硬化杂志,1996,4(1)：20-23.
[80]储利胜,施雪筠,席时芳,等.黄芪皂甙提高心脏保存效果的实验研究[J].中国中西医结合杂志,1999,19(8)：481-483.
[81]汪德清,沈文梅.黄芪三种提取成分对氧自由基作用的影响[J].中国药理学通报,1994,10(2)：129-132.
[82]吴志刚. 川芎嗪药理研究[J].武汉化工学院学报,2003,25(1) ：28-32.
[83]梁爱华,陈明伟.热毒与血栓性疾病的临床相关性分析与探讨[J].中国中药杂志,2008,33(4)：476.
[84]张轶英,金为群,蔡峥,等.清开灵注射液治疗中风病动脉硬化性血栓脑梗塞40例临床观察[J].中国实验方剂学杂志,2003,9(2)：64.
[85]陈宜恒.清开灵注射液治疗冠心病不稳定型心绞痛108例临床观察[J].菏泽医专学报,1996,8(4)：19.
[86]候玉芬,刘明.中药结合清开灵静脉滴注治疗下肢深静脉血栓形成30例报告[J].中国中西医结合外科杂志,1996,2(1)：28.
[87]崔存利,译.日本对黄连解毒汤的药理研究与临床应用概况[J].国外医学·中医中药分册,1992,14(5)：1.
[88]林兴栋,彭胜权,史志云.“热毒”在中风发病中的作用与证治探讨[J].中国中医药信息杂志,2002,9(1)：43.
[89]王永炎.关于提高脑血管疾病疗效难点的思考[J].中国中西医结合杂志,1997,17(2)：195.
[90]刘毅,赵虹,李如奎.缺血性中风从毒论治[J].湖北中医杂志,2001,23(1)：15
[91]Sima A V, Stancu C S, Simionescu M. Vascular endothelium in atherosclerosis [J]. Cell Tissue Res,2009,335 (1):191-203.
[92]Vannini N, PfefferU, Lorusso G. Endothelial cell aging and apoptosis in prevention and disease:E2selectin expression and modulation as a model [J]. Curr Pharm Des,2008,14 (3):221-225.
[93]Holvoet P, Jenny N S, Schreiner P J, et al. The relationship between oxidized LDL and other cardiovascular risk factors and subclinical CVD in different ethnic groups:the Multi-Ethnic Study of Atherosclerosis (MESA) [J]. Atherosclerosis,2007,194 (1):245-252.
[94]Young IS, McEneny J. Lipoprotein oxidation and atherosclerosis. Biochem Soc Trans 29:358-362,2001.
[95]Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 320:915-924,1989.
[96]Steinbrecher UP, Zhang HF, Lougheed M. Role of oxidatively modified LDL in atherosclerosis. Free Radic Biol Med 9:155-168,1990.
[97]Berliner JA, Heinecke JW. The role of oxidized lipoproteins in atherogenesis. Free Radic Biol Med 20:707-727,1996.
[98]Ross R. The pathogenesis of atherosclerosis:a perspective for the1990s. Nature 362:801-809,1993.
[99]Steinberg D. Low density lipoprotein oxidation and its pathobiological significance. [J] Biol Chem 272:20963-20966,1997.
[100]Mehta JL, Chen J, Hermonat PL, Romeo F, Novelli G. Lectin-like, oxidized low-density lipoprotein receptor-1 (LOX-1):a critical player in the development of atherosclerosis and related disorders. Cardiovasc Res 69:36-45,2006.
[101]Itagaki K, Hauser CJ. Sphingosine 1-phosphate, a diffusible Ca2 influx factor mediating store-operated Ca2+entry. J Biol Chem278: 27540□27547,2003.
[102]Hessler JR, Morel DW, Lewis LJ, Chisolm GM. Lipoprotein oxidation and lipoprotein-induced cytotoxicity. Arteriosclerosis 3:215□222, 1983.
[103]Skowasch D, Jabs A, Andrie R, et al. Pathogen burden, inflammation, proliferation and apoptosis in human instent restenosis. Tissue characteristics compared to primary atherosclerosis [J]. J Vasc Res,2004, 41 (6):525-534.
[104]王国平,邓仲端,瞿智玲氧化修饰的低密度和极低密度脂蛋白对巨噬细胞单核趋化蛋白表达的影响中国医学杂志,1997,77(3)：212-215.
[105]邓仲端,瞿智玲平滑肌细胞源性趋化因子的研究.中国动脉硬化杂志,1993,1(1)： 9-12.
[106]瞿智玲,阮秋蓉,朱大和天然及氧化低密度和极低密度脂蛋白促进动脉平滑肌细胞表达巨噬细胞炎性蛋白-α mRNA中国病理生理杂志,2005,21(3)：475-478.
[107]于光耀,邓仲端,瞿智玲氧化修饰脂蛋白对内皮细胞的单核细胞趋化蛋白1表达的影响中华病理学杂志,1998,27：174-177.
[108]张旭明,邓仲端,瞿智玲氧化型低密度和极低密度脂蛋白诱导人血单核细胞表达巨噬细胞炎性蛋白α.中国动脉硬化杂志,2001,9(3)：198-201.
[109]高永红,袁拯忠,牛福玲,等.新清开灵注射液对大鼠脑缺血再灌注损伤微血管内皮细胞黏附分子表达的影响.中华中医药杂志,2008,23(3)：197-200.
[110]Han DK, Haudenschild CC, Hong MK, Tinkle BT, Leon MB, Liau G. Evidence for apoptosis in human atherosclerosis and in a rat vascular in jury model[J]. Am J Pathol,1995,147:2672277.
[111]Hegyi L, Skepper JN, Cary NR, Mitchinson MJ. Foam cell apoptosis and the development of the lipid core of human atherosclerosis [J]. Am J Pathol,1996,18 (4):4232429.
[112]Takuya K, Yoshio T, Mayami M, et al. Roles of thromboxane A2 and prostacyclin in the development of atherosclerosis in apoE deficient mice[J]. Clinical Investigation,2004,114 (6):784-794.
[113]Belton O, Byrne D, Kearney D, et al. Cyclooxygenase-1 and dependent prostacyclin formation in patients with atherosclerosis [J].Circulation,2000,102:840-845.
[114]Gerszten RE, Mach F, Sauty A, et al. Chemokines, Leukocyte and atherosclerosis. J Lab Clin Med,2000,136 (2)187-92.
[115]Beehuizen B, Van Furth R. Monocytes adherence to human vascular endothelium. J Leukoc Biol,1993; 54:363-378.
[116]Jonris N, Zand T. Nunnari J, et al. Studies on the pathogenesis of atherosclerosis.I Adhesion and emigration of mononuclear cells in the aorta of hypercholosterolemic rat. Am J Pathol 1983,113:341.
[117]洪伟,陈铁真.内皮细胞脂质过氧化损伤与单核细胞内皮下传入.中国医科大学学报.1994,23(3)189-193.
[118]Butcher EC Leukocye-endothelial cell recognition:three (or more)steps to specificity and diversity Cell,1991,67:1033-1036.
[119]Jonic N, Jilek P, Bernasconi S, et al.Molecules involved in the adhesion and cytotoxincity of activated monocytes on endothelial cells. J Immunok,1992:148:2080-2083.
[120]Elices MJ, Osborn L, Takada Y, et al. VCAM-1 on activated endothelium interacts with the leucocyte integrim VLA 4 at a snedistinct from the VLA-4 Fibronectin binding cite cell.1990:60:577-584.
[121]Kobayashi M, Inoue K, Warabi E, Minami T, Kodama T. A simple method of isolating mouse aortic endothelial cells. [J] Atheroscler Thromb.2005; 12(3):138-42.
[122]Sakai A, Kume N, Nishi E, et al. P-selectin and vascular cell adhesion molecule-1 are focally expressed in aortas of hypercholesterolemic rabbits before internal accumulation of macrophages and T lymphocytes [J]. Arterioscler Thromb Vase Biol,1997,17 (2): 3102316.
[1]王玉琦,叶建荣.血管外科治疗学[M].上海：上海科学技术出版社2003：136
[2]司徒真强,吴军正.细胞培养[M].西安：世界图书出版西安公司 2007.1
[3]陆德明.中医外科学[M].上海：上海科学技术出版社1997：6
[4]方肇勤.分子生物学技术在中医药研究中的应用[M].上海：上海科学技术出版社2008：9
[5]雷载权.中药学[M].上海：上海科学技术出版社1995：6
[6]许济群,王绵之.方剂学[M].上海：上海科学技术出版社1985：6
[2]李小鹰,王洁,何耀,范利.周围动脉硬化闭塞症在老年血脂异常人群中的现患率调查[J].中华老年心脑血管病杂志2005,2.(7)：3-4.
[3]Hansson GK. Inflammation and atherosclerosis, and coronary artery disease [J]. N Engl J Med,2005,352:1685-1695
[4]Wic, Knoflach M, Xu Q. Autoimmune and inflammatory mechanisms in atherosclerosis [J]. Annu Rev Immunol,2004,22:361-403.
[5]李建华,郭志刚,吴平生,杨永红,赖文岩.血管内皮细胞中ABCA1的表达及其在动脉粥样硬化发生中的意义[J].第一军医大学学报,2004,24,(9)：980-983
[6]马丽,朱文云,李宏妹,邢海燕,金永娟.OX-LDL对内皮细胞粘附分子表达及粘附功能影响的研究[J].微循环学杂志,2000.3(10)：49
[7]危当恒,王贵学,黄华,刘录山,王佐,唐朝克.低密度脂蛋白对血管内皮细胞骨架及粘附能力的影响[J].医用生物学,2006,21,(6)：105-110
[8]林秋雄,余细勇,单志新,林曙光.氧化型低密度脂蛋白对血管内皮细胞ICAM-1 mRNA表达的影响[J].岭南心血管志,2003,9,(4)：282-284.
[9]Callow AD. Endothelial dysfunction in atherosclerosis [J]. Vascul Pharm acol,2002,38 (5):257-258.
[10]Golino P, Piscione F, Willerson JT, et al. Divergent effects of serotonin on coronary artery dimensions and blood flow in patients withcoronary atherosclerosis and control patients [J]. N Engl J Med,1991, 324 (10):641-648.
[11]Lerman A, Holmes DR J r, BellMR, et al. Endothelin in coronary endothelial dysfunction and early atherosclerosis in humans[J]. Circulation,1995,92 (9):2426-2431.
[12]Geisler T, Bhatt DL. The role of inflammation in atherothrombosis: current and future strategies of medical treatment [J]. Med SciMonit,2004, 10(12):RA308-316.
[13]Cybulsky M I, Iiyama K, Li H, et al. A major role for VCAM-1, but not ICAM-1, in early atherosclerosis [J]. J Clin Invest,2001,107(10): 1255-1262.
[14]Boring L, Gosling J, Cleary M, et al. Decreased lesion formation inCCR2-/-mice reveals a role for chemokines in the initiation of atherosclerosis [J]. Nature,1998,394 (6696):894-897.
[15]HermanMP, Sukhova GK, Libby P, et al. Exp ression of neutrophil collagenase (matrixmetalloproteinase28) in human atheroma:a novel collagenolytic pathway suggested. by transcriptionalp rofiling[J]. Circulation,2001,104 (16):1899-1904.
[16]Libby P, Geng YJ, AikawaM, et al. Macrophages and atherosclerotic plaque stability[J]. CurrOpin L ipidol,1996,7 (5):330-335.
[17]Chamorro A. Role of inflammation in stroke and atherothrombosis [J]. Cerebrovasc D is,2004,17 (Supp 13):125.
[18]Ridker PM, StampferMJ, Rifai N. Novel risk factors for systemic atherosclerosis:a comparison of C2reactive p rotein, fibrinogen, homocysteine, lipoprotein (a), and standard cholesterol screening as predictors of peripheral arterial disease[J]. JAMA,2001,285 (19):2481-2485.
[19]Ridker PM, Hennekens CH, Buring JE, et al. C2reactive protein and othermarkers of inflammation in the prediction of cardiovascular disease in women[J]. N Engl J Med,2000,342 (12):836-843
[20]KITAGAWAK, MATSUMOTOM, MABUCHI T, et al. Deficiency of intercellular adhesion molecule-1 attenuates microcirculatory disturbance and infarction sizein focal cerebral ischemia [J]. Cereb Blood Flow Betab, 1998,18(12):336-345
[21]STANIMIROVIC DB, WONG J, SHAPIRO A, et al. Increase in surface expression of ICAM-1, VCAM-1 and E-selectin in human cerebromicrovascular endothelial cells subjected to ischemia-like insults [J]. Acta Neurochir Suppl,1997,70:12-16
[22]Brand K, Page S,Rogler G et al. Activiated transcription factor nuclear Factor-kappaB is present in the atherosclerotic lesion. J Clin Invest,1996; 97(7):1715-1722
[23]Baeuerle PA. The inducible transcription activator NF-kappaB: Regulation by distinct protein subunits. Biochim Biophys Act,1991; 1072 (1):63-80
[24]Dagia NM, Harii N, Meli AE, et al. Phenyl methimazole inhibits TNF-alpha induced VCAM-1 expression in an IFN regulatory factor-1-dependent manner and reduces monocytic cell adhesion to endothelial cells J Immunol 2004,173(3):2041-2049
[25]Lin WN, Luo SF, Lee CW, et al. Involvement of MAPKs and NF-kappaB in LPS-induced VCAM-1 expression inhuman tracheal smooth muscle cells. Cell Signal 2007; 19
[26]Chen YH, Lin SJ, Chen JW, et al. Magnolol attenuates VCAM-lexpression in vitro in TNF-alpha-treated human aortic endothelial cells and in vivo in the aorta of choles terol-fed rabbits. Br J Pharmacol 2002; 135(1):37-47
[27]Hall G, Hasday JD, Rogers TB. Regulating the regulator:NF-kappaB signaling in heart. J Mol Cell Cardiol 2006; 41(4):580-591
[28]Zhong C, Zhou Y, Liu H. Nuclear factor kappaB and anesthetic Preconditioning during myocardial ischemia reperfusion. Anesthesiology2004; 100(3):540-546
[29]Tsurumi Y, Takeshita S,Chen D, et al. Direct intramuscular gene transfer of naked DNA encoding vascular endothelial growth factor augments ollateral development and lissueperfusion [J]. circulation,1996,94 (12):3281
[30]尚德俊,王嘉桔,王书桂.中西医结合周围血管疾病学.海口：南海出社,1995：119—223.
[31]郝群,李大金,朱影,等.补肾宁心方对去势高脂血症家兔主动脉血管细胞粘附因子1表达的调节[J].中国动脉硬化杂志,2004,12(3)：301-304.
[32]郝群,李大全,朱影,等.补肾宁心方对单核-内皮细胞在动脉粥样硬化中相互作用的影响[J].中国老年学杂志,2004,24(4)：337-339.
[33]任钧国,邱全瑛,郝钰,等.清解宁对白细胞-血管内皮细胞粘附的影响[J].中国免疫学杂志,2003,19(4)：618.
[34]周沐科,何俐,吴波,等,大川芎丸对血管内皮细胞中血管内皮生长因子分泌水平的影响[J].中国临床康复,2004,8(19)：3842-3843.
[35]喻嵘,陈大舜,梅志刚,等.左归双降方对葡萄糖胰岛素低密度脂蛋白诱导损伤的血管内皮细胞ICAM-1 tPA PAI的影响[J].中医药学刊,2005,23(1)：61-63.
[36]赵建宏,林琳,曹卉,等.益气活血中药防治大鼠血管内皮细胞损伤的实验研究[J].微循环学杂志,2001,11(2)：36-38.
[37]任勇才.中药制剂治疗血脂异常概况.广西中医学院学报,2004,7(4)64～66.
[38]严瑾,沃兴德,范春雷,等.山楂叶总黄酮对PPARγ-PPRE信号调控系统的影响.中国药学杂志,2005,40(8)：625～628.
[39]任钧国,邱全瑛,郝钰,等.清解宁对白细胞-血管内皮细胞粘附的影响[J].中国免疫学杂志,2003,19(4)：618.
[40]周沐科,何俐,吴波,等,大川芎丸对血管内皮细胞中血管内皮生长因子分泌水平的影响[J].中国临床康复,2004,8(19)：3842-3843.
[41]喻嵘,陈大舜,梅志刚,等.左归双降方对葡萄糖胰岛素低密度脂蛋白诱导损伤的血管内皮细胞ICAM-1 tPA PAI的影响[J].中医药学刊,2005,23(1)：61
[42]赵建宏,林琳,曹卉,等.益气活血中药防治大鼠血管内皮细胞损伤的实验研究[J].微循环学杂志,2001,11(2)：36-38.
[43]王保华,欧阳静萍,魏蕾,等.当归及阿魏酸钠对内皮细胞中TGF β1及bFGF表达的影响[J].辽宁中医杂志,2001,28(1)：45-46.
[44]何晓琳,刘志.青蒿琥酯对脂多糖致血管内皮细胞活化及损伤的保护作用[J].中国中西医结合杂志,2004,24(12)：1110-1113.
[45]郝钰,邱全瑛,吴珺,等.小檗碱对淋巴细胞与血管内皮细胞粘附因子的影响[J].中国免疫学杂志,1999,15(11)：523-525.
[46]郝钰,邱全瑛,吴珺,等.黄芪多糖促进中性粒细胞与血管内皮细胞粘附及相关粘附分子表达[J].中国中西医结合志,2004,24(5)：427-430.
[47]李敏杰,刘永,马琳,等.葛根素对内皮细胞增殖及粘附分子表达的影响[J].陕西中医,2002,23(2)：78-79.
[48]朱雄翔,汤朝武,陈璧.烧伤早期及丹参对中性粒细胞化学发光的影响[J].第四军医大学学报,1999,20(10)：924.
[49]Chen Y H, Lin S J,Ku H H,et al. Salvianolic acid B attenuates VCAM-1 and ICAM-1 expression in TNF alpha-treated human aortic endothelial cells [J]. Cell Biochem,2001,82(3):512.
[50]刘春华,钱冠清,刘会齐,等.银杏叶提取物抑制轻度修饰低密度脂蛋白诱导的血管内皮细胞与单核细胞粘附的实验研究[J].中国中西医结合杂志,2000,20(12)：917.
[51]贺兰萍,高建英,昌艳艳,等.穿心莲对兔胸主动脉内膜损伤后血管内皮细胞中PDGF-B蛋白的表达影响[J].中国老年杂志,2005,25(2)：182-183.
[52]接传红,高健生.中药密蒙花抗血管内皮细胞增生作用的研究[J].眼科,2004.13(6)：348-350.
[53]王云开,苏海,程晓曙.茶色素对培养猪离体主动脉内皮细胞功能影响的实验研究[J].高血压杂志,1999,1(7)：56.
[54]吴德芹,张旭.麦冬药血清对静脉内皮细胞直管调解物质的影响[J].中医药学报,2004,32(2)：40-44.
[55]李民,张旭,朱平,等.麦冬、生地药血清对直管内皮细胞增殖的影响[J].国医论坛,2001,16(5)：83-85.
[56]吴勇,等.黄芪多糖对糖尿病大鼠血管内皮细胞的影响[J].辽宁中医杂志,2002,29, (1)：22-23
[57]李萍等.黄芪多糖对细胞增殖及血管内皮细胞与白细胞粘附作用的影响[J].中国病理生理杂志,2004,20(9)：1677-1680
[58]晏庆德,张学颖.补阳还五汤片剂治疗早期动脉硬化性闭塞症临床研究[J].山杂志东中医,2005.3：140-143
[59]柳国斌等。脉健方治疗肢体动脉粥样硬化闭塞症的临床研究[J].河北中医,2002.1(24)：5-7
[60]刘健齐.清会.通脉冲剂治疗动脉粥样硬化闭塞症的实验研究[J].天津医药,2003.5.(31)：304-306
[61]蒋洪庆.股动脉注射脉络宁等药物治疗下肢动脉硬化性闭塞症[J].中国临床医生,2002.12.
[62]吴文元.川芎嗪治疗周围动脉粥样硬化闭塞症疗效观察[J]实用中医药杂志,2002.8.(18)：5
[63]郝群,李大全,朱影,等.补肾宁心方对单核-内皮细胞在动脉粥样硬化中相互作用的影响[J].中国老年学杂志,2004,24(4)：337-339.
[64]钱小奇.试论高脂血症的病因病机[J].天津中医,2002,19(6)：51.
[65]刘春玲,唐蜀华,孙云霞.芦黄颗粒对实验性动脉粥样硬化家兔C反应蛋白和白细胞介素-6水平的影响[J].中国中西医结合急救杂志,2005,12(6)：366-368.
[66]Vladimir R B, Lei Ding, Jeff R, et al. Cyclooxygenase-1 deficien2cy in bone marrow cells increases early atherosclerosisin apolipopro2tein E and low-density lipoprotein receptornullmice[J].Circulation,2006,113:108-117.
[67]Hansson GK. Inflammation and atherosclerosis, and coronary artery disease[J]. N Engl J Med,2005,352:1685-1695
[68]Wic, Knoflach M, Xu Q. Autoimmune and inflammatory mechanisms in atherosclerosis[J]. Annu Rev Immunol,2004,22:361-403
[71]吕志军,梁绪国.三七总皂苷对血管内皮细胞凋亡及凋亡调控基因的影响[J]1中西医结合心脑血管病杂志,2005,3(11)：975-977.
[72]闫彦芳,张壮,孙塑伦,等.三七总皂苷及其主要成分对血管内皮细胞缺氧损伤的保护作用[J]。中国实验方剂学杂志,2002,8(1)：34-37.
[73]曾桂凤,刘建勋,李澎,等.丹参三七不同配比对缺氧损伤人脐静脉内皮细胞的保护作用[J]精细化工,2006,23(2)：126-129。
[74]文川,徐浩,黄启福,等.活血中药对ApoE基因缺陷小鼠血脂及动脉粥样硬化斑块炎症反应的影响[J].中国中西医结合杂志,2005,25(4)：345-349.
[75]贾乘,张林,程嘉艺,等.三七抑制大鼠血栓形成实验研究[J]1中医药学刊,2001,19(2)：172-173.
[76]李家增,贺石林,王鸿利.血栓病学[M].北京：科学出版社,1998.
[77]王阶,许军,衷敬柏,等.三七总苷对高黏血症患者血小板活化分子表达和血小板聚集的影响[J].中国中西医结合杂志,2004,24(4)：312-316.
[78]谢飞,何恩平,张莉,等.黄芪药理研究进展[J]. 中国药理学通报,1994,15(2)：157-159.
[79]尹小川,刘健康,周序珑,等.三七总皂甙对培养的猪主动脉内皮细胞释放一氧化氮的影响[J].中国动脉硬化杂志,1996,4(1)：20-23.
[80]储利胜,施雪筠,席时芳,等.黄芪皂甙提高心脏保存效果的实验研究[J].中国中西医结合杂志,1999,19(8)：481-483.
[81]汪德清,沈文梅.黄芪三种提取成分对氧自由基作用的影响[J].中国药理学通报,1994,10(2)：129-132.
[82]吴志刚. 川芎嗪药理研究[J].武汉化工学院学报,2003,25(1) ：28-32.
[83]梁爱华,陈明伟.热毒与血栓性疾病的临床相关性分析与探讨[J].中国中药杂志,2008,33(4)：476.
[84]张轶英,金为群,蔡峥,等.清开灵注射液治疗中风病动脉硬化性血栓脑梗塞40例临床观察[J].中国实验方剂学杂志,2003,9(2)：64.
[85]陈宜恒.清开灵注射液治疗冠心病不稳定型心绞痛108例临床观察[J].菏泽医专学报,1996,8(4)：19.
[86]候玉芬,刘明.中药结合清开灵静脉滴注治疗下肢深静脉血栓形成30例报告[J].中国中西医结合外科杂志,1996,2(1)：28.
[87]崔存利,译.日本对黄连解毒汤的药理研究与临床应用概况[J].国外医学·中医中药分册,1992,14(5)：1.
[88]林兴栋,彭胜权,史志云.“热毒”在中风发病中的作用与证治探讨[J].中国中医药信息杂志,2002,9(1)：43.
[89]王永炎.关于提高脑血管疾病疗效难点的思考[J].中国中西医结合杂志,1997,17(2)：195.
[90]刘毅,赵虹,李如奎.缺血性中风从毒论治[J].湖北中医杂志,2001,23(1)：15
[91]Sima A V, Stancu C S, Simionescu M. Vascular endothelium in atherosclerosis [J]. Cell Tissue Res,2009,335 (1):191-203.
[92]Vannini N, PfefferU, Lorusso G. Endothelial cell aging and apoptosis in prevention and disease:E2selectin expression and modulation as a model [J]. Curr Pharm Des,2008,14 (3):221-225.
[93]Holvoet P, Jenny N S, Schreiner P J, et al. The relationship between oxidized LDL and other cardiovascular risk factors and subclinical CVD in different ethnic groups:the Multi-Ethnic Study of Atherosclerosis (MESA) [J]. Atherosclerosis,2007,194 (1):245-252.
[94]Young IS, McEneny J. Lipoprotein oxidation and atherosclerosis. Biochem Soc Trans 29:358-362,2001.
[95]Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 320:915-924,1989.
[96]Steinbrecher UP, Zhang HF, Lougheed M. Role of oxidatively modified LDL in atherosclerosis. Free Radic Biol Med 9:155-168,1990.
[97]Berliner JA, Heinecke JW. The role of oxidized lipoproteins in atherogenesis. Free Radic Biol Med 20:707-727,1996.
[98]Ross R. The pathogenesis of atherosclerosis:a perspective for the1990s. Nature 362:801-809,1993.
[99]Steinberg D. Low density lipoprotein oxidation and its pathobiological significance. [J] Biol Chem 272:20963-20966,1997.
[100]Mehta JL, Chen J, Hermonat PL, Romeo F, Novelli G. Lectin-like, oxidized low-density lipoprotein receptor-1 (LOX-1):a critical player in the development of atherosclerosis and related disorders. Cardiovasc Res 69:36-45,2006.
[101]Itagaki K, Hauser CJ. Sphingosine 1-phosphate, a diffusible Ca2 influx factor mediating store-operated Ca2+entry. J Biol Chem278: 27540□27547,2003.
[102]Hessler JR, Morel DW, Lewis LJ, Chisolm GM. Lipoprotein oxidation and lipoprotein-induced cytotoxicity. Arteriosclerosis 3:215□222, 1983.
[103]Skowasch D, Jabs A, Andrie R, et al. Pathogen burden, inflammation, proliferation and apoptosis in human instent restenosis. Tissue characteristics compared to primary atherosclerosis [J]. J Vasc Res,2004, 41 (6):525-534.
[104]王国平,邓仲端,瞿智玲氧化修饰的低密度和极低密度脂蛋白对巨噬细胞单核趋化蛋白表达的影响中国医学杂志,1997,77(3)：212-215.
[105]邓仲端,瞿智玲平滑肌细胞源性趋化因子的研究.中国动脉硬化杂志,1993,1(1)： 9-12.
[106]瞿智玲,阮秋蓉,朱大和天然及氧化低密度和极低密度脂蛋白促进动脉平滑肌细胞表达巨噬细胞炎性蛋白-α mRNA中国病理生理杂志,2005,21(3)：475-478.
[107]于光耀,邓仲端,瞿智玲氧化修饰脂蛋白对内皮细胞的单核细胞趋化蛋白1表达的影响中华病理学杂志,1998,27：174-177.
[108]张旭明,邓仲端,瞿智玲氧化型低密度和极低密度脂蛋白诱导人血单核细胞表达巨噬细胞炎性蛋白α.中国动脉硬化杂志,2001,9(3)：198-201.
[109]高永红,袁拯忠,牛福玲,等.新清开灵注射液对大鼠脑缺血再灌注损伤微血管内皮细胞黏附分子表达的影响.中华中医药杂志,2008,23(3)：197-200.
[110]Han DK, Haudenschild CC, Hong MK, Tinkle BT, Leon MB, Liau G. Evidence for apoptosis in human atherosclerosis and in a rat vascular in jury model[J]. Am J Pathol,1995,147:2672277.
[111]Hegyi L, Skepper JN, Cary NR, Mitchinson MJ. Foam cell apoptosis and the development of the lipid core of human atherosclerosis [J]. Am J Pathol,1996,18 (4):4232429.
[112]Takuya K, Yoshio T, Mayami M, et al. Roles of thromboxane A2 and prostacyclin in the development of atherosclerosis in apoE deficient mice[J]. Clinical Investigation,2004,114 (6):784-794.
[113]Belton O, Byrne D, Kearney D, et al. Cyclooxygenase-1 and dependent prostacyclin formation in patients with atherosclerosis [J].Circulation,2000,102:840-845.
[114]Gerszten RE, Mach F, Sauty A, et al. Chemokines, Leukocyte and atherosclerosis. J Lab Clin Med,2000,136 (2)187-92.
[115]Beehuizen B, Van Furth R. Monocytes adherence to human vascular endothelium. J Leukoc Biol,1993; 54:363-378.
[116]Jonris N, Zand T. Nunnari J, et al. Studies on the pathogenesis of atherosclerosis.I Adhesion and emigration of mononuclear cells in the aorta of hypercholosterolemic rat. Am J Pathol 1983,113:341.
[117]洪伟,陈铁真.内皮细胞脂质过氧化损伤与单核细胞内皮下传入.中国医科大学学报.1994,23(3)189-193.
[118]Butcher EC Leukocye-endothelial cell recognition:three (or more)steps to specificity and diversity Cell,1991,67:1033-1036.
[119]Jonic N, Jilek P, Bernasconi S, et al.Molecules involved in the adhesion and cytotoxincity of activated monocytes on endothelial cells. J Immunok,1992:148:2080-2083.
[120]Elices MJ, Osborn L, Takada Y, et al. VCAM-1 on activated endothelium interacts with the leucocyte integrim VLA 4 at a snedistinct from the VLA-4 Fibronectin binding cite cell.1990:60:577-584.
[121]Kobayashi M, Inoue K, Warabi E, Minami T, Kodama T. A simple method of isolating mouse aortic endothelial cells. [J] Atheroscler Thromb.2005; 12(3):138-42.
[122]Sakai A, Kume N, Nishi E, et al. P-selectin and vascular cell adhesion molecule-1 are focally expressed in aortas of hypercholesterolemic rabbits before internal accumulation of macrophages and T lymphocytes [J]. Arterioscler Thromb Vase Biol,1997,17 (2): 3102316.
[1]王玉琦,叶建荣.血管外科治疗学[M].上海：上海科学技术出版社2003：136
[2]司徒真强,吴军正.细胞培养[M].西安：世界图书出版西安公司 2007.1
[3]陆德明.中医外科学[M].上海：上海科学技术出版社1997：6
[4]方肇勤.分子生物学技术在中医药研究中的应用[M].上海：上海科学技术出版社2008：9
[5]雷载权.中药学[M].上海：上海科学技术出版社1995：6
[6]许济群,王绵之.方剂学[M].上海：上海科学技术出版社1985：6
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |