Role of c-Abl in myocardial ischemia-reperfusion injury in diabetic rats / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the role of c-Abl in myocardial ischemia-reperfusion (I/R) injury in diabetic rats.Methods:Sixty male SPF-grade healthy Sprague-Dawley rats, aged 7-9 weeks, weighing 210-230 g, were divided into 6 groups by a random number table method: sham operation group (S group, n=6), myocardial I/R group (IR group, n=12), diabetic sham operation group (DS group, n=6), diabetic myocardial I/R group (DIR group, n=12), diabetic myocardial I/R plus AVV9-siRNA-c-Abl group (DIR+ c-Abl group, n=12), and diabetic myocardial I/R plus AVV9-GFP group (DIR+ GFP group, n=12). One percent streptozotocin 60 mg/kg was intraperitoneally injected to induce type 1 diabetes mellitus.AVV9-siRNA-c-Abl and AVV9-GFP 1×10 12 mg/kg were slowly injected at 4 weeks after establishing the model in DIR+ c-Abl and DIR+ GFP groups.Myocardial ischemia was induced by 30 min occlusion of left anterior descending branch (LAD) of coronary artery followed by 2 h reperfusion at 8 weeks after establishing the model.At the end of reperfusion, left ventricular systolic pressure (LVSP) and the maximum rate of increase and decrease of left ventricular systolic pressure (±dp/dt max) were monitored, and blood samples were collected for determination of the concentrations of serum lactic dehydrogenase (LDH) and creatine kinase-MB (CK-MB) (by enzyme-linked immunosorbent assay)and myocardial infarct size (except group S and group DS). Myocardial tissues were obtained for determination of the apoptosis index of cardiomyocytes(by TUNEL staining), expression of c-Abl, p53 and activated caspase-3 (by Western blot), and binding of c-Abl and p53 (c-Abl/p53) (by co-immunoprecipitation method). Results:LVSP and ±dp/dt max were significantly decreased, serum LDH and CK-MB concentrations were increased, apoptosis index and c-Abl/p53 were increased, and the expression of c-Abl, p53 and activated caspase-3 was up-regulated in group IR when compared with group S and in group DIR as compared with group DS ( P<0.05). Compared with group DIR, the LVSP and ± dp/dt max were significantly increased, serum LDH and CK-MB concentrations were decreased, myocardial infarct size was decreased, apoptosis index and c-Abl/p53 were decreased, and the expression of c-Abl, p53 and activated caspase-3 was down-regulated in group DIR+ c-Abl ( P<0.05), and no significant change was found in the parameters mentioned above in group DIR+ GFP ( P>0.05). Conclusion:c-Abl is involved in the pathophysiological process of myocardial I/R injury probably by activating p53 signaling pathway in diabetic rats.