静脉表型分子COUP-TFⅡ表达降低对血管内皮细胞衰老的影响  

Effect of venous marker COUP-TFⅡ knockdown on senescence of vascular endothelial cells

作　　者：赖亚宇[1] 周骐[2] 郑微 靳鹏[1] 顾文竹 武晓静[1] LAI Ya-yu;ZHOU Qi;ZHENG Wei;JIN Peng;GU Wen-zhu;WU Xiao-jing(Cardiology Center o f PLA, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China;Cardiovascular Department o f The Second Ajfiliated Hospital o f Chongqing Medical University, Chongqing 400010, China)

机构地区：[1]第三军医大学附属新桥医院全军心血管内科中心,重庆400037 [2]重庆医科大学第二附属医院心内科,重庆400010

出　　处：《中国病理生理杂志》2017年第8期1345-1352,共8页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81370404;No.91539104)

摘　　要：目的:观察静脉表型分子鸡卵清蛋白上游启动子转录因子Ⅱ(COUP-TFⅡ)表达对血管内皮细胞衰老的影响和分子机制。方法:通过RT-qPCR检测比较人冠状动脉内皮细胞(HCAEC)和人脐静脉内皮细胞(HUVEC)中COUP-TFⅡ的表达情况。使用10^(-5)mol/L血管紧张素Ⅱ(AngⅡ)诱导HUVEC衰老,通过COUP-TFⅡ特异性小干扰RNA(siCOUP-TFⅡ)转染HUVEC使其COUP-TFⅡ的表达降低,利用β-半乳糖苷酶染色、Western blot、CCK-8、细胞计数等方法分别观察siCOUP-TFⅡ对AngⅡ诱导的血管内皮细胞衰老及增殖的影响,通过Western blot检测Akt信号分子的表达变化。结果:与HCAEC相比,HUVEC中COUP-TFⅡ呈显著高表达;用siCOUP-TFⅡ抑制HUVEC的COUP-TFⅡ表达时,能显著促进AngⅡ诱导的内皮细胞衰老并抑制内皮细胞增殖和p-Akt蛋白水平;加入Akt激动剂SC79(4 mg/L)能够部分逆转siCOUP-TFⅡ对AngⅡ诱导的HUVEC衰老和增殖的影响。结论:COUP-TFⅡ表达降低可促进血管内皮细胞衰老并抑制内皮细胞增殖,其机制可能与调节Akt信号有关。AIM:To investigate the effect of venous marker chicken ovalbumin upstream promoter-transcriptionfactor II(COUP-TF II)expression on vascular endothelial cell senescence and its molecular mechanism.METHODS:The mRNA expression of COUP-TF II in the human coronary artery endothelial cells(HCAEC)and human umbilical veinendothelial cells(HUVEC)was detected by RT-qPCR.After transfection with a COUP-TF II siRNA(siCOUP-TF II)toinhibit COUP-TF II expression in the HUVEC,the senescence and proliferation of endothelial cells were evaluated by pgalactosidasestaining,Western blot,CCK-8assay and cell counting after treatment with105mol/L angiotensin II(AngII).The protein levels of Akt and p-Akt were determined by Western blot.RESULTS:Compared with the HCAEC,COUP-TF II was significantly highly expressed in the HUVEC.Knockdown of COUP-TF II via siCOUP-TF II significantlyinduced endothelial cell senescence and inhibited endothelial cell proliferation and p-Akt level after treatment with Ang II at105mol/L.Furthermore,an Akt activator SC79at4mg/L partly reversed the effect of siCOUP-TF II on Ang II-inducedendothelial cell senescence and proliferation.CONCLUSION:Knockdown of COUP-TF II promotes endothelial cell senescenceand inhibits endothelial cell proliferation,which might be partly regulated by Akt signaling.

关 键 词：动脉粥样硬化 血管内皮细胞 细胞衰老 细胞增殖 鸡卵清蛋白上游启动子转录因子Ⅱ 

分 类 号：R339.38[医药卫生—人体生理学] R363.21[医药卫生—基础医学]