Expression Of Rho-kinase In Rats With Acute Myocardial Infarction And Its Effect On Apoptosis

Objective:To analyze the changes of Rho-kinase expression in rats with myocardial infracted and to study the relationship between the 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 hours and the survival rats were randomly divided into two groups, treated group and AMI group. Another ten rats were randomly selected as the sham-operated group,with no ligation of LAD. Fasudil 5mg/kg were given into the rats of the treated group twice a day by intraperitoneal injection and the rats of the AMI group and sham-operated group during the same period were given an equivalent normal saline. After 4-weeks treatment, hemodynamic pararmeters(Left ventricular systolic pressure(LVSP), Left ventricular end diastolic pressure (LVEDP), The maximum rising and dropping rates of left ventricular pressure (+dp/dtmax.-dp/dtmax)) were measured with catheterization. The Rho kinase mRNA expression in the ischemia region was measured by RT-PCR. The Bcl-2 and Bax protein expressions were measured by immunohistochemical staining; the apoptotic cardiocytes in the ischemia region were determined by the DNA ladder analysis.Results:(1)Compared with the sham rats, all MI rats showed marked worsening in hemodynamic parameters(LVSP and+dp/dtmax,-dp/dtmax were decreased, LVEDP were increased), and all MI rats showed marked increase in Rho-kinase mRNA and apoptosis-related proteins Bax, and decrease in bcl-2 (P<0.01); DNA agarose gel electrophoresis of all MI rats formed ladders, but no ladders were observed in sham group.(2)Compared with the AMI group, the hemodynamics of treated group improved, and the expression of Rho-kinase mRNA and bax decreased, bcl-2 increased, all the differences were significant (P＜0.05,<0.01).Conclusion:(1) Apoptosis is the main form of cardiac myocyte death in the ischemia and non-ischemic myocardial around the infarct area, and it plays an important role in the continuous loss of myocardial cells and the deterioration of cardiac function; (2) Rho-kinase inhibitor fasudil able to inhibit the expression of Rho-kinase mRNA, and increase the expression of apoptosis-related proteins Bcl-2 and decrease the expression of Bax, thereby reducing cell apoptosis and improving hemodynamic parameters, and to protect the myocardium.