辛伐他汀防治心肌细胞肥大效应及其与钙通道关系的研究  

The effects of simastatin on calcium channels in preventing cardiac hypertrophy

作　　者：耿鹏[1] 吴扬[1] 杨惠超[1] 刘娟[1] 

机构地区：[1]南通大学航海医学研究所,南通226001

出　　处：《南通大学学报（医学版）》2010年第1期24-27,F0002,共5页Journal of Nantong University(Medical sciences)

基　　金：南通市应用基础研究项目(K2006023)

摘　　要：目的:探讨辛伐他汀对心肌细胞肥大的防治作用及其与钙通道活动的关系。方法:采用血管紧张素Ⅱ诱导新生大鼠心肌细胞肥大模型。应用改良Lowry法测定心肌细胞总蛋白含量。相差显微镜测定心肌细胞表面积。CCK-8法检测心肌细胞活力变化。westernblot方法检测心肌细胞L-型钙通道亚单位Cav1.2(α1C)、T-型钙通道亚单位Cav3.1(α1G)、Cav3.2(α1H)蛋白表达的变化。应用激光共聚焦显微镜技术检测[Ca2+]i的变化。结果:(1)辛伐他汀能明显抑制AngⅡ诱导的心肌细胞总蛋白含量及细胞表面积的增加,同时提高心肌细胞活力;(2)辛伐他汀能明显降低心肌细胞T-型钙通道α1G、α1H蛋白表达,但对L-型钙通道α1C蛋白表达无明显影响;(3)辛伐他汀可呈剂量依赖性抑制心肌细胞肥大所致的钙离子超载。结论:辛伐他汀对AngⅡ诱导的心肌细胞肥大具有明显的防治作用,其作用机制可能与辛伐他汀抑制T-型钙通道α1G、α1H蛋白的重新再表达有关,并与其抑制细胞内钙超载密切相关。Objective：To investigate the effects of simvastatin on calcium channels in preventing cardiac hypertrophy.Methods：Total protein content was measured by Lowary,s method and the cell surface area was measured by phase contrast microscope.CCK-8 method was used to observe the viability of myocardiocytes.The expression of α1C、α1G and α1H were detected by western blot.Intracellular Ca2＋ were measured with Fluo-3/AM under confocal laser microscope.Results：The total protein content and cell size of cardiomyocytes increased significantly and the cardiomyocyte viability decreased in Ang Ⅱ treated cells and these effects could be blocked by simvastatin.The protein of α1G and α1H were significantly increased after AngⅡtreatment,which could be inhibited by simvastatin or verpamil hydrochloride.But the protein level of L-type calcium channel α1C was no significant difference between each group.Intracellular calcium overload was remarkably inhibited by simvastatin with a concentration-dependent manner.Conclusions：SIM can inhibit Ang Ⅱ-induced cardiomyocyte hypertrophy,which may be related to the inhibition of the increasing of T-type calcium channel subunit α1G、α1H,and meanwhile to the inhibition of calcium overloading.

关 键 词：心肌细胞肥大 T-型钙通道 L-型钙通道 辛伐他汀 

分 类 号：R541.3[医药卫生—心血管疾病]