同型半胱氨酸诱导内皮细胞凋亡caspase3途径作用的机制  

Homocysteine-induced apoptosis of endothelial cells and roles of caspase3

作　　者：徐志红[1] 陆国平[2] 邹琛[2] 吴春芳[2] 

机构地区：[1]上海交通大学医学院瑞金医院老年病科,上海200025 [2]上海交通大学医学院瑞金医院心脏科,上海200025

出　　处：《上海交通大学学报（医学版）》2007年第1期67-71,共5页Journal of Shanghai Jiao tong University:Medical Science

基　　金：上海市科委基金(054119634)~~

摘　　要：目的了解同型半胱氨酸(Hcy)是否通过caspase途径诱导内皮细胞凋亡,以及辛伐他汀是否可以通过调节c-IAP行使其拮抗效应。方法Hcy、辛伐他汀或两者联合处理人脐静脉内皮细胞(HUVEC)24 h后,采用Annexin V染色加流式细胞术及TUNEL观察细胞凋亡状态;RT-PCR和蛋白质印迹技术检测caspase3、c-IAP-1和c-IAP-2的mRNA和蛋白质水平。结果0.5 mmol/L和3 mmol/L的Hcy均导致HUVEC凋亡,Hcy浓度高时凋亡细胞数较高,并伴有caspase3表达和活化增强;c-IAP-1、c-IAP-2的mRNA和蛋白质水平降低;辛伐他汀可以上调c-IAP-1和c-IAP-2的表达。结论Hcy诱导HUVEC凋亡作用可能涉及caspase3相关途径;辛伐他汀可促进c-IAP系统的表达,从而部分拮抗Hcy的作用。Objective To investigate whether homocysteine （Hey） induces apoptosis of endothelial cells via a pathway involving caspases3 and whether simvastatin antagonizes the proapoptotic effects of Hey by regulating c-IAP. Methods Human umbilical vein endothelial cells（HUVEC） were treated with Hey,with or without simvastatin,for 24 h. Cell apoptosis was evaluated by Annexin V staining and flow cytometery, as well as TUNEL. The mRNA and protein levels of caspase3 ,c-IAP-1 and c-IAP-2 were analyzed by RT-PCR and Western blot, respectively. Results Treatment with both low （0.5 mmol/L） and high （3.0 mmol/L） concentrations of Hcyinduced HUVEC apoptosis was accompanied by an increased level of caspase3 expression and activation, together with decreased c-IAP- 1 and c-IAP-2 level. Simvastatin upregulated e-IAP-1 and c-IAP-2 expression while attenuated Hey-induced apoptosis and caspase3 activation. Conclusion Hey may induce HUVEC apoptosis via a pathway involving caspase3,which can be partially antagonized by simvastatin, possibly through upregulated c-IAP-1 and c-IAP-2 expression.

关 键 词：同型半胱氨酸 辛伐他汀 细胞凋亡 CASPASE3 c-IAP 

分 类 号：R543.5[医药卫生—心血管疾病]