Role of caspase-3 dependent hepatocyte apoptosis in liver ischemia-reperfusion injury in cirrhotic rats / 中国病理生理杂志

ABSTRACT

AIM: To investigate whether hepatocyte apoptosis is contributed to liver ischemia-reperfusion (I/R) injury and the relationship between liver caspase-3 activity and hepatocyte apoptosis in cirrhotic rats. METHODS: Liver ischemia-reperfusion is induced by Pringle maneuver. The cirrhotic rats were randomized into two groups Group A simple hepatic blood inflow occlusion (HBIO); Group B HBIO + inhibitor, before HBIO, ZVAD-fmk 15 mg/kg was injected via dorsal penis vein; Group C healthy rat, simple HBIO. The ischemia time was 30 min in these groups. Serum aspartate aminotransferase(AST), liver caspase-3 activity, and apoptotic hepatocytes were examined in the three groups. RESULTS: After 6 h of reperfusion, the liver caspase-3 activity was markedly elevated and reached its peak, which was statistically higher than that of before I/R ［(18.1±1.8 ) μmol*h-1*g-1 (tissue) vs (6.6±2.0) μmol*h-1*g-1 (tissue), P＜0.01］. The same change occurred in hepatocyte apoptosis between 6 h of reperfusion and before I/R (20.9%±4.9% vs 0.5%±0.3%, P＜0.01). As the reperfusion prolonged, the caspase-3 activity and apoptotic hepatocyte decreased gradually. The 7th-day survival rate was 62.5% in group A. The serum AST, liver caspase-3 activity and apoptotic hepatocytes were significantly higher in group A than those in group B and C, representing the most severe liver injury among the three groups. CONCLUSION: Hepatocyte apoptosis is the major form of cell death in liver ischemia-reperfusion injury in cirrhotic rats. Hepatoctye apoptosis induced by I/R is caspase-3 dependent, and inhibiting caspase-3 can alleviate liver injury. The caspase-3 dependent hepatocyte apoptosis is highly contributed to the pathological phenomenon that the ischemic sensitivity of cirrhotic liver is higher than normal liver.