Protective Effect And Mechanism Of Sufentanil Preconditioning On Hepatic Ischemia-reperfusion Injury: By Activating P38Mitogen-activated Protein Kinases Signal Pathway

Objective: To study the protective effect of sufentanil preconditioning on hepatic ischemiareperfu-sion injury in rats.Methods: One hundred and fifty SD rats(in either gender, weighing250-300g) were randomly dividedinto five groups: Sham-operated group（S）, ischemia-reperfusion group（I/R）; sufentanil preconditioninggroups（SF1:1μg/kg; SF5:5μg/kg; SF10:10μg/kg）. In sufentanil preconditioning groups, different dosesof sufentanil were injected30minutes before ischemia-reperfusion, group S and group I/R were givenequal volume of saline. Sample specimens were collected from group I/R and group SF at0h,1h,2h,4hand6h after reperfusion. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST)were measured by an automatic biochemical analyzer. Malondialdehyde (MDA) and superoxide dismutase(SOD) in liver tissue was measured. HE staining was used to observe the hepatic pathological changes.Liver sample specimens at2h after reperfusion from each group above were selected. In group SB (SB203580, an inhibitor of p38MAPK) and DMSO (dimethyl sulphoxidecontrol), liver sample specimenswere collected at2h. Examined the expression of phosphor-p38mitogen-activated protein kinases（p-p38MAPK）of liver sample specimens by western blotting．Results: Except group S, the levels of serum ALT and AST in other groups were significantly increasedwith the extension of ischemia-reperfusion time, and reached a peak at4hours, then decreased gradually.Compared with group I/R, levels of AST and ALT showed significantly decreased in group SF(p<0.05);Compared with group SF1, levels of AST and ALT showed significantly decreased in group SF5(p<0.05). Compared with group SF5, levels of AST and ALT showed significantly decreased in groupSF10(p<0.05).Compared with group I/R, levels of MDA in liver tissue decreased significantly in group SF, while levelsof SOD increased (p<0.05); Compared with group SF1, levels of MDA showed significantly decreased andlevels of SOD increased in group SF5(p<0.05),Compared with group SF5, levels of MDA showedsignificantly decreased and levels of SOD increased in group SF10(p<0.05).In the group I/R, obvious pathological changes were observed in the liver: swelling and necrosis of livercells, inflammatory cell infiltration and hepatic venous congestion; Compared with group I/R, group SFdecreased liver congestion gently, the structure of hepatic lobule was normal, liver cells had no obviousdegeneration, hepatic venous congestion was reduced.The expression of p-P38MAPK protein: group S only expressed trace. In group I/R, the visible traceexpression of p-p38MAPK increased with the extension of ischemia-reperfusion time, reached the peak at2hours. In the sufentanil preconditioning groups and SB203580groups, the expression of p-p38MAPKdecreased obviously (p<0.05). There was no significant difference between group DMSO and group I/R(p>0.05).Conclusion: Sufentanil preconditioning can reduce the hepatic ischemia-reperfusion injury. The protectivemechanisms may be by Inhibitting p38MAPK signal pathway to promote p38MAPK phosphorylation sothat to reduce the expression of inflammatory factors.