多种病理因素对血管内皮细胞增殖与凋亡的影响及VEGF的干预作用  

Inhibitory Effect of Vascular Endothelial Growth Factor on Proliferation and Apoptosis of Vascular Endothelial Cells Induced by Pathological Factors

作　　者：刘佳妮[1] 程燕子[1] 廖德荣[1] 曾艳[1] 叶珊[1] 刘启功[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院心内科,武汉430030

出　　处：《华中科技大学学报（医学版）》2009年第5期608-611,共4页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：湖北省自然科学基金资助项目(No.2003ABA135)

摘　　要：目的研究缺氧、H2O2、氧化型低密度脂蛋白(OX-LDL)和肿瘤坏死因子-α(TNF-α)对血管内皮细胞(VEC)增殖、凋亡和凋亡相关基因表达的影响及血管内皮生长因子(VEGF)的干预作用,探讨VEGF预防经皮冠状动脉介入治疗(PCI)后再狭窄和支架内血栓形成的机制。方法将VEC分成对照组、缺氧处理组、缺氧+VEGF处理组、H2O2处理组、H2O2+VEGF处理组、OX-LDL处理组、OX-LDL+VEGF处理组、TNF-α处理组和TNF-α+VEGF处理组。利用四氮唑盐比色法检测各组细胞吸光度值,观察VEC增殖情况,采用原位末端标记法和流式细胞术观察各组细胞凋亡情况,通过RT-PCR法了解各组细胞凋亡相关基因Bcl-2与Apo-1/Fas mRNA表达情况。结果缺氧、H2O2、OX-LDL和TNF-α处理组凋亡细胞和Apo-1/Fas mRNA表达明显多于对照组和相应VEGF处理组,而细胞增殖和Bcl-2 mRNA表达则明显低于对照组和相应VEGF处理组(均P<0.01)。结论缺氧、H2O2、OX-LDL和TNF-α能抑制VEC增殖,诱导VEC凋亡,而VEGF能部分拮抗上述作用,其抗凋亡作用可能与Bcl-2 mRNA表达上调和Apo-1/Fas mRNA表达下调有关,为VEGF用于预防PCI后再狭窄和支架内血栓形成进一步提供了理论依据。Objective To evaluate the mechanisms of vascular endothelial growth factor（VEGF）on prevention of restenosis and stent thrombosis after percutaneous coronary intervention（PCI）by observing the effect of VEGF on the proliferation and apoptosis of vascular endothelial cells（VEC）induced by hypoxia,H2O2,OX-LDL and TNF-α.Methods VEC were divided into control group,hypoxia-treated group,hypoxia ＋VEGF-treated group,H2O2-treated group,H2O2＋VEGF-treated group,OX-LDL-treated group,OX-LDL＋VEGF-treated group,TNF-α-treated group,and TNF-α＋VEGF-treated group.The absorbance（A）value of VEC was examined by WST-1 method,the apoptosis of VEC measured by in situ terminal deoxynucleotidyl transferase（TdT）-mediated deoxyuridine triphosphate（dUTP）-biotin nick end-labeling（TUNEL）and flow cytometry（FCM）,and the expression of Bcl-2 mRNA and Apo-1/Fas mRNA detected by reverse transcription polymerase chain reaction（RT-PCR）.Results As compared with control group and VEGF-treated group,the apoptosis cells and the expression of Apo-1/Fas mRNA were significantly increased in hypoxia-,H2O2-,OX-LDL-and TNF-α-treated groups,but the A value of VEC and the expression of Bcl-2 mRNA were markedly decreased.Conclusion VEGF could inhibit the proliferation and apoptosis of VEC induced by hypoxia,H2O2,OX-LDL and TNF-α,which might be correlated with up-regulation of Bcl-2 mRNA expression and down-regulation of the Apo-1/Fas mRNA expression.

关 键 词：血管内皮生长因子 血管内皮细胞 细胞增殖 细胞凋亡 凋亡相关基因 

分 类 号：R543.31[医药卫生—心血管疾病]