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Telmisartan延缓血管内皮细胞衰老及p21INK4a表达变化的作用

发表时间:2015-06-15  浏览量:1616  下载量:538
全部作者: 单海燕,韦晓洁,何旖旎,祁慧萌,于凯,于晓松
作者单位: 中国医科大学附属第一医院全科医学科
摘 要: 目的:探讨替米沙坦(Telmisartan)对血管紧张素Ⅱ(angiotensin Ⅱ,AngⅡ)诱导的人脐血管内皮细胞衰老与p21INK4a表达变化的影响,为寻求延缓内皮细胞衰老途径提供理论和实验依据。方法:体外培养人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVECs),予AngⅡ及Telmisartan干预。实验分为空白对照组、AngⅡ诱导组及Telmisartan组,采用β-半乳糖苷酶(β-gal)染色鉴定细胞衰老;流式细胞术分析细胞周期变化;免疫细胞化学染色法分析各组细胞p21INK4a 的阳性染色率,Western blotting分析各组细胞p21INK4a蛋白的表达。结果:与对照组比较,AngⅡ诱导组β-gal阳性染色率显著增多(82.04±6.58)%,细胞周期停滞于G0-G1期(89.20±6.52)%,p21INK4a蛋白表达水平上调(P<0.05);予以Telmisartan干预后,β-gal阳性细胞染色率减少,G0-G1细胞减少,p21INK4a蛋白表达水平下调(P<0.05)。结论:血管内皮细胞衰老分子机制可能通过下调p21INK4a的表达,使细胞周期停滞于G1期,Telmisartan对血管内皮细胞衰老有一定保护作用,可能通过调控p21INK4a的表达发挥其延缓血管内皮细胞衰老的作用。
关 键 词: 医学细胞生物学;血管紧张素Ⅱ;内皮细胞;血管衰老;细胞周期;p21INK4a
Title: Study on Telmisartan delaying endothelial cell senescence and gene expression of p21INK4a
Author: SHAN Haiyan, WEI Xiaojie, HE Yini, QI Huimeng, YU Kai, YU Xiaosong
Organization: Department of General Practice, First Affiliated Hospital, China Medical University
Abstract: Objective: To investigate the role of Telmisartan on angiotensin Ⅱ (AngⅡ)-induced sene瑂cence of human umbilical endothelial cell senescence and gene expression of p21INK4a and to provide theoretical and experimental foundation on delaying endothelial cell senescence. Methods: Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and intervened by AngⅡ (10"6 mol/L) and Telmisartan. HUVECs were divided into 3 groups, which are called control group, AngⅡ group and Telmisartan group. β-gal staining was used to identify cell aging status. Flow cytometry was used for analyzing the cell cycle changes. The positive cell rate of p21INK4a was detected by immunocytochemical staining and the expressions of p21INK4a protein were determined by Western blotting. Results: Compared with the control group, the positive cell number of β-gal staining is significantly higher in AngⅡ-induced cells (82.04±6.58)%; the cell cycle blocked at G0-G1 (89.20±6.52)%, p21INK4a protein expression increases evidently (P<0.05). In Telmisartan group, the positive cell number of β-gal staining is decreased and the cells of G0-G1 is reduced while p21INK4a protein expression decreases evidently (P<0.05) compared to that in the AngⅡ group. Conclusion: Cell endothelial cell senescence is induced by AngⅡ. One of its molecular mechanisms might be associated with increasing the expression level of p21INK4a in aging cell, and then up-regulating the amount of cells blocking in G1 phase of cell cycle. Telmisartan can antagonize the process effectively and delay endothelial cell aging significantly.
Key words: medical cell biology; angiotensinⅡ; endothelial cell; vascular aging; cell cycle; p21INK4a
发表期数: 2015年6月第11期
引用格式: 单海燕,韦晓洁,何旖旎,等. Telmisartan延缓血管内皮细胞衰老及p21INK4a表达变化的作用[J]. 中国科技论文在线精品论文,2015,8(11):1136-1140.
 
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