Role of c-Jun N-terminal kinase signal pathway in sufentanil preconditioning against hepatic ischemia-reperfusion inj ury in rats / 临床麻醉学杂志

ABSTRACT

Objective To detect the protective effect of sufentanil preconditioning on hepatic ischemia-reperfusion injury in rats and the role of c-Jun N-terminal kinase signal pathway in the mech-enism.Methods One hundred and sixty-two SD rats(in either gender,weighing 250-300 g)were ran-domly divided into seven groups:Sham-operated group (group S,n = 30 ),ischemia-reperfusion group (group IR,n =30),sufentanil preconditioning group (group SF1:1 μg/kg,n =30;group SF5:5 μg/kg,n =30;group SF10:10 μg/kg,n =30),SP600125 group (group SP,n =30),and dimethyl sulphoxide control group (group DMSO,n =6),different doses of sufentanil was administered 30 min before hepatic ischemia in group SF1,SF5 and SF10.Blood and liver samples were collected from each group at 0(T1 ),1 (T2 ),2 (T3 ),4 (T4 ),and 6 (T5 )hours after reperfusion.Serum alanine amin-otransferase (ALT)and aspartate aminotransferase (AST)were measured by an automatic biochemi-cal analyzer.Malondialdehyde (MDA)and superoxide dismutase (SOD)in liver tissue was measured. Liver sample was stained with HE to observe the hepatic pathological changes.Immunohistochemical method was used to determine the expression of JNK and western blotting was used to detect the ex-pression of P-JNK.Results Compared with group S,levels of AST,ALT increased significantly in group IR,SF1,SF5,SF10 at T1-T5 and in group SP,DMSO at T3 (P <0.05 ).Compared with group IR,levels of AST,ALT decreased significantly in group SF1,SF5,SF10 at T1-T5 and in group SP at T3 (P <0.05).Compared with group S,levels of MDA,SOD increased significantly in group IR,SF1, SF5,SF10 at T1-T5 and in group SP,DMSO at T3 (P < 0.05 ).Compared with group IR,levels of MDA,SOD decreased significantly in group SF1,SF5,SF10 at T1-T5 and in group SP at T3 (P <0.05).Compared with group SF1 and SF5,levels of MDA,SOD decreased significantly in SF10 at T4 . Compared with T1 ,the expression of p-JNK in group IR increased significantly at T3 (P < 0.05 ). Compared with group S,the expression of p-JNK in groups IR,SF1,SF5,SF10,SP,DMSO increased significantly at T3 (P < 0.05 ).Compared with group IR,the expression of p-JNK in groups SF1, SF5,SF10,SP decreased significantly and that in groups SF5,SF10 were less than that in group SF1 (P <0.05 ).The expression of p-JNK in group SF10 was less than that in group SF5 (P < 0.05 ). Conclusion Sufentanil preconditioning can reduce the hepatic ischemia-reperfusion injury and the dos-age of 10 μg/kg was the most effective.The protective mechanisms may inhibit JNK pathway and re-duce the expression of JNK.