Modified Mild Heat Shock Modality Attenuates Hepatic Ischemia/Reperfusion Injury

Background Hepatic ischemia/reperfusion (I/R) injury is a pathologic process caused by hepatic surgery and transplantation, and still remains a severe clinical problem. It was shown that preconditioning by hyperthermia might protect tissues against I/R injury. But hyperthermia could be laborious and time-consuming. Alternatively, the application of mild electrical stimulation (MES) has been reported to have positive effects in clinical settings on several medical ailments. Thus, we modified the preconditioning approach by combining short-term mild heat shock (HS) and MES, and evaluated the effect of HS + MES pretreatment on hepatic injury induced by I/R. Materials and Methods C57BL/6 J mice were sham treated or treated three times with HS (42°C) and/or MES (12 V) for 20 min, carried out every other d within 1 wk. After the last treatment, mice were subjected to hepatic ischemia for 30 or 60 min and reperfusion for 6 h. Liver injury was assessed by evaluating the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The expressions of pro-inflammatory cytokines and heat shock protein (Hsp) 72 in liver tissues were also assessed by real-time PCR and Western blotting analyses, respectively. Results HS + MES pretreatment suppressed the hepatic I/R-induced release of serum AST and ALT and the mRNA levels of some pro-inflammatory cytokines. In addition, HS + MES up-regulated the expression of Hsp72 in mice liver. Conclusions HS + MES preconditioning ameliorated hepatic I/R injury possibly through Hsp72 induction, and suppressed pro-inflammatory cytokine expression in mice liver.