Protective effect of sinomenine on ischemia-reperfusion injury during orthotopic liver transplantation in rats / 第二军医大学学报

ABSTRACT

Objective: To investigate the protective effect of sinomenine on the cold ischemia/reperfusion injury during orthotopic liver transplantation (OLT) in rats. Methods: OLT were performed in normal rats using Kamada's two-cuff technique. The rats were randomly divided into sham operation, control and two sinomenine groups. Animals in sinomenine groups were treated with low (40 mg/kg) or high dose (80 mg/kg) of sinomenine. The serum and tissue samples of rats in each group were collected 2, 6, 12, and 24 h after reperfusion,and the one-week survival rate was observed. The apoptosis index (AI) of liver cells after OLT was detected by TUNEL. The expression of TNF-α and IL-Iβ mRNA in the liver were detected by RTPCR. Results: Compared with the control group, the level of ALT was significantly decreased in the two sinomenine treatment groups at different time points after transplantation, and their one-week survival rates were also significantly increased (75%, 75% vs 12.5%, P<0.01). Compared with the control group, the AI of liver cells was markedly decreased in sinomenine treatment groups (P<0.01). Sinomenine treatment also significantly decreased the expression of TNF-α and IL-1β mRNA (P< 0.01) and greatly ameliorated the focal necrosis of hepatocytes and sinusoidal endothelial cells (SECs). Conclusion: Sinomenine can inhibit hepatocyte apoptosis by inhibiting the synthesis of TNF-α and IL-1β. sinomenine can prevent hepatic cells and SECs from cold ischemia/reperfusion injury during orthotopic liver transplantation in rats.