叶酸拮抗同型半胱氨酸诱导的内皮细胞凋亡的作用机制

目的： 明确同型半胱氨酸（Hcy）对内皮细胞凋亡的影响以及叶酸的拮抗作用，阐明Bax和Bcl-2在同型半胱氨酸诱导内皮细胞凋亡及叶酸拮抗中的作用。方法: 用不同浓度的Hcy处理内皮细胞后，应用末端转移标记技术（TUNEL）以及Annexin V/PI染色加流式细胞术了解细胞凋亡状态，免疫组化方法检测Bax、Bcl-2的表达。结果: Hcy能促进细胞凋亡，叶酸具有拮抗作用。Hcy能促进细胞Bax、Bcl-2的表达，上调Bax/Bcl-2比值，叶酸能减少细胞表达Bax及Bcl-2，下调Bax/Bcl-2比值。结论: Bax、Bcl-2参与了Hcy诱导内皮细胞凋亡以及叶酸拮抗作用的过程。

Mechanism underlying the antagonistic effect of folic acid on homocysteine-induced apoptosis in endothelial cell

AIM: To investigate the effects of homocysteine(Hcy) on apoptosis in SV40-transformed aortic rat endothelial cell line and the anti-apoptosis effects of folic acid.METHODS: Cells were treated with different concentrations of Hcy and folic acid,apoptosis was detected by TUNEL and annexin-V/ PI staining methods.Immunohistochemical assay was used to examine the expression of Bax and Bcl-2 in all groups.RESULTS: Both annexin-V/PI staining and TUNEL method showed that Hcy increased endothelial apoptosis in a dose-dependent manner,while folic acid reduced cell apoptosis.Hcy increased expression of Bax and Bcl-2 in endothelial cells,and folic acid decreased it.Bax/Bcl-2 ratio in 0.5 mmol/L Hcy and 5.0 mmol/L Hcy group were upregulated compared with control group(P<0.05 and P<0.01,respectively).Addition of 0.1 mmol/L folic acid decreased Bax/Bcl-2 ratio compared with the corresponding group without folic acid(P<0.05).Correlation analysis showed a strong relation between Bax/Bcl-2 ratio and apoptotic rate(P<0.01).CONCLUSION: Folic acid attenuates the apoptosis induced by Hcy in endothelial cells.Hcy may promote endothelial cell apoptosis via upregulation of Bax /Bcl-2 ratio,which can be partially antagonized by folic acid.