Role of mPTP in hepatocytes in reduction of hepatic ischemia-reperfusion injury by limb ischemic postconditioning in rats

Abstract

Objective To evaluate the role of mitochondrial permeability transition pore (mPTP) in hepatocytes in reduction of hepatic ischemia-reperfusion (I/R) injury by limb ischemic postconditioning in rats. Methods Forty-eight healthy male Sprague-Dawley rats, weighing 240-280 g, were randomly divided into 4 groups (n=12 each) using a random number table: sham operation group (group S); I/R group; limb ischemic postconditioning group (group LIPC); limb ischemic postconditioning and atractyloside group (group LIPC + APC). In I/R, LIPC and LIPC + APC groups, I/R injury was induced by 30 min occlusion of the hepatic artery and portal vein entering the left and middle lobes of the liver, followed by 120 min of reperfusion. The animals underwent 10 min of bilateral limb ischemia starting from 20 min after liver ischemia in group LIPC. In group LIPC+ APC, the animals underwent 10 min of bilateral limb ischemia starting from 20 min after liver ischemia, and atractyloside 5 mg/kg was infused simultaneously via the penile vein. Blood samples were collected from inferior vena cava at the end of reperfusion to detect plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. The rats were sacrificed, and the left lobe of the liver was removed to detect the degree of mPTP opening and to examine the ultrastructure of hepatocytes under electron microscope. Results Compared with group S, the plasma ALT and AST activities and degree of mPTP opening were significantly increased, and the damage to the ultrastructure of hepatocytes was obvious in the other three groups. Compared with group I/R, the plasma ALT and AST activities and degree of mPTP opening were significantly decreased, and the damage to the ultrastructure of hepatocytes was reduced in LIPC and LIPC+ APC groups. Compared with group LIPC, the plasma ALT and AST activities and degree of mPTP opening were significantly increased in group LIPC+ APC. Conclusion Limb ischemic postconditioning reduces hepatic I/R injury through inhibiting mPTP opening in hepatocytes of rats. Key words: Mitochondrial membrane transport proteins; Ischemic postconditioning; Reperfusion injury; Liver