Liver ischemic preconditioning in mice-implications of HSP27 induction to ameliorate ischemiareperfusion injury / 中华器官移植杂志

ABSTRACT

ObjectiveTo explore the role of HSP27 in hepatic ischemia-reperfusion (IR) injury and hepatic ischemic preconditioning (IP).MethodsMale C57BL/6 mice were randomly divided into 3 groups:control group (sham operation),IR group (only hepatic IR),rHSP27 + IR group (rHSP27 injection before IR).The extent of liver injury was evaluated among these 3 groups.Murine HSP27 was silenced by short hairpin RNA and mice were subjected to IR with or without IP after interfering succeeded.Serum ALT and AST levels,hepatic histological damages and mRNA expression levels of pro-inflammatory mediators (TNF-α,IL-1β and IL-6) were measured.Results Silencing hepatic HSP27 aggravated IR injury indicated by higher concentration of serum ALT and AST (P＜0.05),reinforced by severer histological damage and more expression of pro-inflammatory mediators (P＜0.05),while injection of rHSP27 or IP ameliorated hepatic IR injury.Western-blot showed HSP27 expression was significantly higher in IP group than sham group.Silencing HSP27 largely removed the IP-induced hepatoprotection,indicated by restoration of caspase-3 induction.ConclusionHSP27 is an essential endogenous defense of liver against IR injury.Hepatic ischemic preconditioning can improve subsequent IR injury via up-regulation of HSP27,which is related to HSP27-mediated reduction of apoptosis.