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钙通道阻滞剂改善内质网应激抑制压力过负荷高血压大鼠的心肌重构

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2012年第6期
页码:
686-690,701
栏目:
基础研究
出版日期:
2012-12-25

文章信息/Info

Title:
Protective effect of calcium channel blocker on hypertensive rat myocardial remodeling of pressure overload induced by endoplasmic reticulum stress
作者:
槐 勇; 赵连友; 李 炜; 郑强荪; 刘 静; 郭 丽; 丁 璐
(第四军医大学唐都医院心血管内科，陕西 西安 710038)
Author(s):
HUAI Yong;  ZHAO Lian-you;  LI Wei;  ZHENG Qiang-sun;  LIU Jing;  GUO Li;  DING Lu
(Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, Shaanxi, China)
关键词:
拉西地平; 内质网应激; 心肌重构; 高血压; 细胞凋亡; 大鼠
Keywords:
lacidipine;  endoplasmic reticulum stress;  myocardium hypertrophy;  CRT;  caspase-12;  apoptosis
分类号:
R972.3
DOI:
-
文献标识码:
A
摘要:
目的:研究在压力过负荷应激状态下钙通道阻滞剂拉西地平对内质网应激（endoplasmic reticulum stress，ERS）分子钙网蛋白（calreticulin，CRT）和细胞凋亡效应分子-12(caspase-12)在大鼠心肌组织中的表达及对心肌重构的影响。方法： 将30只雄性Sprague-Dawly(SD)大鼠随机分为3组，即假手术组(Sham组)、腹主动脉缩窄组（TAC组）及TAC＋拉西地平干预组（简称拉西地平组），每组10只。通过颈动脉插管测定各组大鼠的血流动力学，心脏超声心动图检查左心室的形态结构。采用免疫组化染色法检测大鼠心肌中CRT及caspase-12蛋白的表达水平，TUNEL荧光染色法检测心肌细胞的凋亡率。结果： 与Sham组相比较，TAC组大鼠的平均动脉压(MAP)、室间隔厚度(IVST)、左室后壁厚度(LVPWT)、左室质量指数(LVWI)、CRT和caspase-12蛋白表达水平及心肌细胞的凋亡率比较，均有显著升高(P<0.01)。拉西地平组大鼠MAP、IVST、LVPWT、LVWI、CRT和caspase-12蛋白的表达水平及心肌细胞的凋亡率较TAC组明显下降(P<0.05)。结论： 内质网应激可能参与了压力过负荷高血压大鼠心肌重构的过程。钙通道阻滞剂拉西地平可能通过降低CRT及caspase-12的表达及减少心肌细胞的凋亡干预ERS介导的压力负荷所致高血压大鼠心肌肥厚的信号通路，从而通过改善内质网应激发挥对心脏的保护作用。
Abstract:
AIM:To investigate the influence of calcium channel blocker lacidipine on the expression of calreticulin (CRT) and caspase-12 in rat cardiac myocytes and the effects of lacidipine against myocardium remodeling under pressure overload conditions. METHODS: Thirty male Sprague Dawley rats were randomly divided into TAC group (transverse aortic constriction), control group (sham group) and TAC+lacidipine group with ten rats in each group. Invasive hemodynamics were measured through carotid cannulation and left ventricular morphology was monitored by echocardiography. Expressions of CRT and caspase-12 in rat cardiac myocytes were examined by immunohistochemistry, and cardiac myocyte apoptosis was detected by TUNEL fluorescent staining. RESULTS: Compared with those in control group, MAP (mean arterial pressure), IVST (interventricular septal thickness), LVPWT (left ventricular posterior wall thickness), LVWI (left ventricular weight index), expressions of CRT and caspase-12 in cardiac myocytes, and incidence of cardiac myocyte apoptosis remarkably increased in TAC group (P<0.01). Compared with those in TAC group, MAP, IVST, LVPWT, LVWI and incidence of cardiac myocyte apoptosis in TAC+lacidipine group decreased significantly, whereas expressions of CRT and caspase-12 in cardiac myocytes were significantly downregulated (P<0.05). CONCLUSION: The endoplasmic reticulum stress may be involved in the process of myocardium remodeling caused by pressure overload induced-hypertension. Lacidipine may exert a protective effect on the heart by ameliorating the endoplasmic reticulum stress via downregulating the expression of CRT and caspase-12 and decreasing the incidence of cardiac myocyte apoptosis.

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备注/Memo

备注/Memo:
收稿日期：2012-02-22.通讯作者：赵连友，主任医师，主要从事高血压发病机制及相关疾病防治的研究 Email:zhaolyfmmu@yahoo.com.cn 作者简介：槐勇，主治医师，博士生 Email:huaiyong0926@yahoo.com.cn
更新日期/Last Update: 2012-12-30