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|本期目录/Table of Contents|

辛伐他汀对缺氧/复氧诱导的心肌细胞凋亡的拮抗作用及其作用机制

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2011年第2期
页码:
189-192,213
栏目:
基础研究
出版日期:
2010-12-10

文章信息/Info

Title:
Protective effects and mechanism of simvastatin on hypoxia/reoxygenation-induced apoptosis in rat cardiomyocyte
作者:
张申伟; 高好考; 陈江红; 李聪叶; 潘云虎; 曹丰; 郭文怡
第四军医大学西京医院心内科，陕西 西安 710032
Author(s):
ZHANG Shen-wei;  GAO Hao-kao;  CHEN Jiang-hong;  LI Cong-ye;  PAN Yun-hu;  CAO Feng;  Guo Wen-yi
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China
关键词:
辛伐他汀; 缺氧/复氧; 凋亡; TLR4; 心肌细胞
Keywords:
simvastatin;  hypoxia/reoxygenation;  apoptosis;  TLR4;  cardiac myocytes
分类号:
R972.6
DOI:
-
文献标识码:
A
摘要:
目的: 探讨辛伐他汀对缺氧/复氧诱导的心肌细胞损伤的拮抗作用及潜在机制。方法： 分离培养 Sprague-Dawley(SD)大鼠(乳鼠)心肌细胞,随机分为对照组、缺氧2h/复氧4h(H/R4h)组、不同浓度(0.1、1.0及10 μmol/L)的辛伐他汀干预组及Toll样受体4(TLR4)中和性抗体MTS510组(浓度为10 μg/L)。H/R4h组给予缺氧2 h后，随即复氧4 h。细胞处理后，进行PI-AnnexinV染色用流式细胞仪检测心肌细胞的凋亡率，用ELISA法检测心肌乳酸脱氢酶(LDH)的活性；用免疫印迹法测TLR4蛋白的含量。结果:与H/R4h组相比,辛伐他汀干预组可显著降低心肌细胞的凋亡率(16.0% vs. 28.6%,P<0.01)及LDH 的活性(P<0.01)，并呈剂量依赖性。中浓度的辛伐他汀组开始出现拮抗作用，峰值出现在高浓度辛伐他汀组, 加入MTS510阻断剂可降低心肌细胞的凋亡率及LDH的活性(P<0.01)。结论:辛伐他汀对H/R造成的心肌细胞损伤具有拮抗作用,并呈剂量依赖性,其作用机制可能与TLR4信号通路有关。
Abstract:
AIM: To explore the protective effects and mechanism of simvastatin on hypoxia/reoxygenation-induced cardiac injury. METHODS: Cultured cardiomyocytes from neonatal rats subjected to hypoxia for 2 h and reoxygenation for 4 h were divided randomly into four groups: control group, hypoxia 2h/reoxygenation 4 h group (H/R4h), simvastatin (SIM) pretreated group (concentration: 0.1 μmol/L, 1 μmol/L, 10 μmol/L), and neutralizing antibody group of TLR4: MTS510 (10 μg/L). Cardiomyocyte apoptosis was detected by flow cytometry, concentration of LDH was measured by ELISA and expression of TLR4 protein was measured by Western blot. RESULTS: Compared with that in control and H/R4h groups, H/R-induced apoptosis was markedly attenuated in SIM group in a dose-dependent manner. Protective effects of simvastatin began at 0.1 μmol/L and the maximal effects reached at 10 μmol/L. After the addition of neutralizing antibody of TLR4, cardiocyte apoptosis and activities of LDH decreased. CONCLUSION: Simvastatin protects hypoxia/reoxygenation-induced cardiac injury in a dose-dependent manner, and the protective effects are in association with TLR4 signalling pathway.

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备注/Memo

备注/Memo:
收稿日期：2010-04-13.通讯作者：郭文怡，主任医师， 主要从事冠心病介入治疗研究Email:guowenyi@tom.com 共同通讯作者：曹丰，教授，主要从事分子影像及干细胞治疗的研究Email:wind8828@gmail.com 作者简介：张申伟，硕士生Email:free214@sina.com
更新日期/Last Update: 2010-12-10