辛伐他汀对血管紧张素Ⅱ诱导心肌成纤维细胞增殖及胶原合成的作用及机制  

The Effects and Mechanism of Simvastatin on Angiotensin Ⅱ Induced Myocardial Fibroblasts Proliferation and Collagen Synthesis

作　　者：王海鹏[1] 

机构地区：[1]苏州大学附属第一医院心内科,江苏苏州215006

出　　处：《中国血液流变学杂志》2011年第4期573-575,578,共4页Chinese Journal of Hemorheology

摘　　要：目的探讨辛伐他汀对血管紧张素Ⅱ诱导的新生大鼠心肌成纤维细胞增生、胶原合成的影响。方法用消化法对新生SD大鼠心肌成纤维细胞做传代培养，实验均采用第二代或第三代细胞。在10^-6mol／L血管紧张素Ⅱ刺激的基础上用辛伐他汀（10^-7、10r6、10^-5Smmol／L）及辛伐他汀（10。、10“mol／L）＋甲羟戊酸（2×10。mol／L）共育，对各组用MTTIZ色法测成纤维细胞增殖能力，应用羟脯氨酸比色法测定羟脯氨酸含量。结果1．AngII刺激乳鼠心肌细胞48h后应用MTT法测得吸光度值、羟脯氨酸含量较正常对照组明显升高（P〈0．05）；而辛伐他汀各浓度之间差别不明显。3．血管紧张素Ⅱ、10^-5mol／L或10^-44mol／L辛伐他汀与甲羟戊酸共同刺激成纤维细胞后，上述指标均与AngII刺激组无统计学差异（P〉0．05）。结论1．AnglI刺激乳鼠心肌成纤维细胞增殖和胶原分泌。2．辛伐他汀可以抑制AngⅡ诱导的心肌成纤维细胞增殖和胶原分泌，其作用可能通过甲羟戊酸途径和下调TGF．BlmRNA表达实现。Objective To investigate the effects and mechanism of simvastatin on angiotensin Ⅱ induced myocardial fibroblasts proliferation in newborn rats and explore the potential molecular mechanism.Methods The neonatal rat myocardial fibroblasts were extracted by enzymatic digestion and anchorage velocity-depen- dent separation method.CFs were divided into seven groups：control group,Ang Ⅱ group,different concentration simvastatin（10Tmol/L,106mol/L,10＂Smol/L）＋Ang Ⅱ group,different concentration simvastatin（10Smol/L,10＂4mol/ L）＋ Ang lI ＋ mevalonic acid（MVA）group.After 48 hours treatment,the cells of each group were collected and the flowing measures were carried out：CFs proliferation was measured by thiazolyl blue（MTT） assay;Collagen syn- thesis in the CFs was assessed with hydroxyproline.Result 1.Compared with control group,MTT values of CFs were increased in Ang Ⅱ group.Hydroxyproline content was up-regulated.2.Compared with Ang Ⅱ group,MTT values of CFs were decreased in a dose-dependent manner in simvastatin ＋ Ang Ⅱ group;Hydroxyproline content was significantly down-regulated,however there were no significant differences among simvastatin groups.3.There were no significant differences in the following index including MTT values,hydroxyproline content of CFs be- tween Ang Ⅱ group and MVA＋simvastatin＋Ang Ⅱ group.Conclusion 1.Ang II stimulate the proliferation of CFs and collagen synthesis.2.Simvastatin can suppress Ang Ⅱ induced proliferation of CFs,3.Mevalonate can reverse the effect of simvastatin, it may suggest that simvastatin work by suppressing mevalonate pathway.

关 键 词：血管紧张素Ⅱ 辛伐他汀 新生大鼠心脏成纤维细胞 甲羟戊酸 

分 类 号：R542.23[医药卫生—心血管疾病]