Expression of Rho-kinase in rats with acute myocardial infarction and its relationship to apoptosis

AIM: To analyze the changes of Rho-kinase expression in rats with acute myocardial infarction (AMI) and to study the relationship between cardiac myocyte apoptosis and Rho/Rock signaling pathway and the effect of fasudil, a Rho kinase selective inhibitor, on cardiac protection after AMI. METHODS: Male Wistar rats were subjected to left anterior descending coronary artery (LAD) ligation for 24 h and the surviving rats were randomly divided into two groups: treatment group (n=12) and AMI group (n=12). Another ten rats were randomly selected as the sham-operated group (n=10), with no ligation of LAD. Fasudil (5 mg/kg) was given to rats of the treatment group twice a day by IP injection. Rats of the AMI group and sham-operated group during the same period were given an equivalent normal of saline. Rats were sacrificed 4 weeks after and the infarct size and ischemia size were determined by Evans-blue and NBT double staining. The Rho kinase mRNA expression in the ischemia region was measured by RT-PCR and the apoptotic cardiocytes in the ischemia region were determined by DNA ladder analysis. Bcl-2 and Bax protein expressions were measured by immunohistochemical staining. RESULTS: Infarct size was obviously reduced in treatment group compared with AMI group (P<0.05) and no significant difference was observed in the ischemic area. The expression of Rho kinase increased significantly in AMI group compared with sham group. Expression of apoptosis-related protein and bax increased whereas bcl-2 decreased (P<0.01). Compared with those in AMI group, the expression of Rho kinase significantly attenuated, bax decreased and bcl-2 increased in the treatment group (P<0.01). DNA agarose gel electrophoresis of both AMI group and treatment group formed ladders, but no ladders were observed in sham group. CONCLUSION: In the myocardium of rats with AMI, the expression of Rho kinase and the apoptosis of myocardial cells are increased. Fasudil, a Rho kinase inhibitor, attenuates the expression of Rho kinase and apoptosis of myocardial cells and decreases infarct size, therefore playing an important role in cardiac protection after AMI.