| Purpose: To investigate the expression and significance of Sigma-1 receptor in mice liver ischemia reperfusion injury.Methods:1.C57BL/6 mice were divided into control group,ischemia for 1 h and reperfusion for 6 h,12 h,24 h group.RT-PCR and Western blot were used to detect the m RNA and protein expression levels of Sigma-1 receptor in liver tissues of different group 2.C57BL/6 mice were randomly divided into control group,hepatic ischemia reperfusion group,Sigma-1 receptor agonist group,Sigma-1 receptor agonist and antagonist group.The mice were pretreated respectively with 4-PPBP or NE-100 1hour before ischemia.The control group and liver ischemia reperfusion group were received the equal amount of normal saline.The protein expression levels of Sigma-1 receptor in liver tissue of different group were detected by Western-blot.The degree of mice liver function injury was determined by serum AST,ALT content and pathological changes of liver tissue.The m RNA expression levels of TNF-α,IL-6 and IL-10 in liver tissues of mice was detected by RT-PCR.The serum levels of TNF-α,IL-6 and IL-10 were detected by Elisa assay.5.The protein expression levels of p38 and p-p38 in liver tissue of different treatment group were assessed by Western-blot.Results: 1.Compared with the control group,the expression levels of Sigma-1 receptor in the liver tissue of liver ischemia reperfusion group was significantly higher than sham operation group.The expression levels of Sigma-1 receptor were upregulated after ischemia 1 hour and 6 hours,12 hours and 24 hours after reperfusion and peaked at 12 hours after reperfusion.2.Sigma-1 receptor expression levels in the liver tissue of mice pretreated with 4-PPBP were significantly higher than liver ischemia reperfusion group,Compared with Sigma-1 receptor agonist group,The reduced expression levels of Sigma-1 receptor were observed in Sigma-1 receptor agonist and antagonist group.The serum AST and ALT levels in liver ischemia reperfusion group were significantly higher than control group.Sigma-1 receptor agonist pretreatment significantly reduced serum AST and ALT levels compared to the liver ischemia reperfusion group.The serum AST and ALT levels of Sigma-1 receptor agonist and antagonist group were higher than the Sigma-1 receptor agonist group.Compared with the liver ischemiareperfusion group,4-PPBP pretreatment could downregulate the m RNA expression levels of TNF-α and IL-6 and upregulate the m RNA expression levels of IL-10.The serum TNF-α,IL-6 levels were decreased,serum IL-10 levels were elevated by 4-PPBP pretreatment,and Sigma-1 receptor antagonist NE-100 blocked this effect.The protein expression levels of pp38 in the liver ischemia reperfusion group was higher than those in control group.The protein expression levels of p-p38 in Sigma-1 receptor agonist group were higher than the liver ischemia reperfusion group.Conclusion:(1)The expression levels of Sigma-1 receptor in liver tissue of mice with hepatic ischemia-reperfusion were significantly increased.(2)The activation of Sigma-1 receptor could alleviate hepatic ischemia reperfusion induced inflammatory response and down-regulate the expression of pro-inflammatory cytokines,upregulate the expression of anti-inflammatory cytokines by inhibiting the activation of p38 MAPK pathway. |
