摘要
目的 探讨阿托伐他汀预处理对垂体后叶素致冠状动脉痉挛大鼠心肌超微结构及冠状动脉RhoA活性的影响.方法 50只SD大鼠随机分为5组,正常组（无特殊处理）、对照组（生理盐水）、阿托伐他汀组（5 mg·kg^-1·d^-1）、硝苯地平组（5 mg·kg^-1·d^-1）和联合用药组（阿托伐他汀5 mg·kg^-1·d^-1＋硝苯地平5 mg·kg^-1·d^-1）.除正常组外,其余四组连续灌胃15d后,经鼠尾静脉注入垂体后叶素1.5 U/kg,诱发冠状动脉痉挛.应用透射电镜观察大鼠心肌细胞超微结构变化;应用Western Blot方法测定大鼠冠状动脉细胞膜RhoA蛋白表达水平和细胞浆RhoA蛋白表达水平,以细胞膜RhoA与细胞浆RhoA比值表示RhoA活性,比较各组大鼠冠状动脉RhoA活性.结果 ①心肌细胞超微结构：对照组心肌细胞超微结构明显破坏;硝苯地平组及阿托伐他汀组大鼠心肌细胞超微结构的破坏程度较对照组明显减轻;联合用药组大鼠心肌细胞超微结构没有明显破坏.②冠状动脉RhoA活性：与正常组相比,对照组冠状动脉RhoA活性明显升高（2.55±0.15比0.81±0.16,P＜0.01）;与对照组相比,阿托伐他汀组冠状动脉RhoA活性明显减低（0.99±0.34比2.55±0.15,P＜0.01）,硝苯地平组冠状动脉RhoA活性未见明显改变（2.21±0.23比2.55±0.15,P=0.08）,联合用药组冠状动脉RhoA活性明显减低（1.13±0.42比2.55±0.15,P＜0.01）.结论 阿托伐他汀预处理能有效预防垂体后叶素诱发大鼠冠状动脉痉挛,保护心肌细胞,与硝苯地平联合应用具有协同作用.抑制RhoA/Rho激酶信号通路的活性参与阿托伐他汀预防冠状动脉痉挛,保护心肌细胞.
Objective The present study was undertaken to investigate the protective effects and mechanisms of atorvastatin on pituitrin-induced coronary artery spasm in rats. Methods Fifty male SD rats were randomly assigned to five groups （n=10）： normal group（no any intervention）, control group （saline）, atorvastatin group （5mg·kg^-1·d^-1）, nifedipine group （5mg·kg^-1·d^-1）, and combined group （atorvastatin 5mg·kg^-1·d^-1 and nifedipine 5mg·kg^-1·d^-1）. After 15 days of treatment by intragastric administration（except the normal group）, coronary artery spasm was induced by injecting pituitrin（1.5 U？kg-1） through caudal vein. The ultrastrueture of myocardial tissue was observed by electron microscopy. The membrane RhoA protein expression and cytosolic RhoA protein expression of coronary artery tissue was detected by western blot, and RhoA activity was expressed as the ratio of membrane RhoA protein and cytosolic RhoA protein. Results 1. Pituitrin-induced coronary artery spasm caused the acute myocardial ischemic/anoxic injury, which result in myocardial ultrastructure damage. Prophylactic use atorvastatin had a protective role in coronary artery spasm induced myocardial ultrastructure damage, and combined with nifedipine was more effective. 2. Compared with the normal group, coronary artery RhoA activity in the control group was significantly increased （2.55±0.15 vs 0.81±0.16, P〈0.01）. Compared with the control group, coronary artery RhoA activity was significantly decreased in the atorvastatin group（0.99±0.34 vs 2.55±0.15, P〈0.01）, no statistically difference in the nifedipine group （2.21±0.23 vs 2.55±0.15, P=0.08）, and significantly decreased in the combined group（1.13±0.42 vs 2.55±0.15, P〈0.01）. Conclusion Atorvastatin could effectively prevent pituitrin-induced coronary artery spasm, and had protective effect on myocardial ultrastructure in rats. The addition of atorvastatin to nifedipine had synergistic effect. Inhibition of RhoA/Rho-kinase pathway involve in the mechanism of atorvastatin preventing coronary artery spasm.
作者
苏林博
谢莲娜
王凯君
王丽君
党凤强
张一凡
SU Lin-bo XIE Lian-na WANG Kai-jun et al(Department of Circulation, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, China)
出处
《中国心血管病研究》
CAS
2016年第11期1052-1055,F0003,共5页
Chinese Journal of Cardiovascular Research
