雌激素对肿瘤坏死因子诱导的内皮细胞凋亡的影响

Influence of estrogen on TNFα induced apoptosis of endothelial cells

观察 17β 雌二醇 (E2 )及肿瘤坏死因子 (TNFα)对培养的人脐静脉内皮细胞 (HUVEC)凋亡的影响。方法 将HUVEC分为 4组 ,空白对照组、TNFα(4 0 μg L)组、TNFα(4 0 μg L)加E2 (1μmol L)和E2 (10 μmol L)组 ,各组细胞经维持液培养 48h使细胞生长同步 ,加入相应药物培养 2 4h后收获细胞。采用免疫组化方法测定bcl 2蛋白表达及流式细胞仪测定细胞凋亡发生百分率。结果 TNFα诱导的细胞凋亡发生率较正常对照组明显增多 (P <0 .0 0 1) ,bcl 2蛋白表达少 ,DNA直方图上可见高大的凋亡峰 ,而雌激素干预后凋亡发生率明显降低 (P <0 .0 0 1) ,bcl 2蛋白表达增加。结论 E2 可增加bcl 2蛋白的表达 ,抑制TNFα诱导的人内皮细胞细胞凋亡的发生率 ,维持内皮细胞结构和功能的完整 ,可能为其抗动脉粥样硬化的机制之一。

Obsjective To investigate the effects of 17β estradiol(E 2) and tumour necrosis factor alpha (TNFα)on the apoptosis of cultured human umbilical vein endothelial cells(HUVEC).Methods HUVEC were divided into four groups:control group,TNFα(40 μg/L) group,TNFα(40 μg/L) with E 2(1 μmol/L) group and E 2(10 μmol/L) group.Cells were gained after all groups were cultured for 24 hours.The apoptosis was assessed by flow cytometry and the expression of bcl 2 protein was measured by immunohistochemical method.Results Compared with control,HUVEC apoptosis increased significantly (P<0.01) and bcl 2 protein expression decreased in TNFα (40 μg/L) group.17β estradiol (1 μmol/L,10 μmol/L) reduced the apoptosis induced by TNFα(P<0.001) and dincreased the expression of bcl 2 protein.Conclusions 17β Estradiol could downregulate the TNFα induced apoptosis of HUVEC and maintain integrity of endothelium,suggesting that estrogen may possess antiatherosclerotic ability.