| Objective: The ventricular remodeling after acute myocardial infarction (AMI), and then the heart failure (HF), eventually lead to death. Currently, there is no effective treatment to prevent it, so the prevention of ventricular remodeling is essential. Recent studies have shown that cardiomyocyte apoptosis is an imperative form of death and it play an important role in ventricular remodeling after acute myocardial infarction. Rho-kinase mediated a series of behavior of cell biology, including cell apoptosis.In this study,myocardial infarction area,cardiomyocyte apoptosis and the expression of Bcl-2 and Bax were obtained after acute myocardial infarction(AMI) in rats,and to study the protection effects of different doses fasudil,a Rho-kinase inhibitor ,on the myocardium of rats with AMI.Methods: Fifty-four healthy male SD rats were subjected to left anterior descending coronary artery(LAD) ligation and were divided randomly into five groups:Sham operation group(not ligation of LAD) ,AMI group, high dose fasudil treated(HDFT) group, intermediate dose fasudil treated(IDFT) group and Low dose fasudil treated (LDFT)group. 1h before surgery the rats received intraperitoneal injection normal saline 0.5ml ( sham group and AMI group) ,30mg/kg fasudil (HDFT group), 10mg/kg fasudil(IDFT group) and 1mg/kg fasudil(LDFT group). At 24 hours after coronary ligation,the rats were sacrificed.The myocardial infarction area and ischemia area were determined by evans-bule and TTC double staining.The cardiocyte apoptosis in the ischemia region was determined by TUNEL assay and the apoptotic index(AI) were calculated.The Bcl-2 and Bax protein expressions were measured by immunohistochemical staining.Results: 1 Compared with the AMI group, the myocardial infarction area reduced obviously in HDF group and IDF group(P <0.01);There was not statistically significant between LDF group and AMI group(P >0.05);Compared with the LDF group, the myocardial infarction area reduced obviously in IDF group(P<0.01).2 Compared with the Sham group, the expression of Bcl-2 reduced obviously in AMI group, LDF group, IDF group and HDF group(P <0.01);Compared with the AMI group, the expression of Bcl-2 increased obviously in HDF group and IDF group(P <0.01);There was not statistically significant between AMI group and LDF group(P >0.05);Compared with the IDF group, the expression of Bcl-2 increased obviously in HDF group(P<0.01). Compared with the LDF group, the expression of Bcl-2 increased obviously in LDF group(P<0.01).3 Compared with the Sham group, the expression of Bax increased obviously in AMI group, LDF group, IDF group and HDF group(P <0.01);Compared with the AMI group, the expression of Bax reduced obviously in LDF group, IDF group and HDF group(P <0.01);Compared with the IDF group, the expression of Bax reduced obviously in HDF group(P<0.01). Compared with the LDF group, the expression of Bax reduced obviously in IDF group(P<0.01).4 Compared with the Sham group, the cardiomyocyte apoptotic index increased obviously in AMI group, LDF group, IDF group and HDF group(P <0.01);Compared with the AMI group, the cardiomyocyte apoptotic index reduced obviously in LDF group, IDF group and HDF group(P <0.01);Compared with the IDF group, the cardiomyocyte apoptotic index reduced obviously in HDF group(P<0.01). Compared with the LDF group, the cardiomyocyte apoptotic index reduced obviously in IDF group(P<0.01).Conclusion: Different Doses Fasudil intervention after AMI in rats can be illustnated as follows, (1) increase the expression of Bcl-2.(2) reduce the expression of Bax.(3) reduce the Cardiocyte apoptosis.(4) reduce the myocardial infarction area. These effects has dose-dependently, and the higer dose the better results. |
