Effect of ischemia-reperfusion induced HMGB1 release on P38 MAPK signaling pathway in mouse liver

Objective To explore the effect of HMGB1 release on P38 MAPK signaling pathway induced by ischemia-reperfusion (IR) in mouse liver. Methods C57BL/6 mice included sham operation group (Sham), IR group (IR) and HMGB1 release inhibitor group (GA). The serum AST, TNF-α and HMGB1 level of the mice were determined using a commercial assay kit. Histopathological changes were observed in mice livers by HE staining. HMGB1, p-P38, P38 and Caspase-3 expression were detected by immunohistochemistry and Western blot, while cell apoptosis was detected by TUNEL assay. Results Compared with Sham group, serum ALT (423.4±99.6), TNF-α (84.3±21.4) and HMGB1 (0.79±0.04) levels were increased in IR group, but decreased in GA group (P<0.05). The histological changes in the livers of the IR group included hepatocyte swelling, hepatic sinusoids narrowing and hepatocyte necrosis, which were alleviated in GA group. Compared with Sham and GA groups, there was a significant increase on HMGB1 transposition and release, and cell apoptosis [(59.3±9.1)%] in IR group (P<0.05), but GA decreased the HMGB1 level in hepatocyte. The expression of HMGB1, p-P38 and Caspase-3 were up-regulated in IR group compared with those in Sham and GA groups (P<0.05). Conclusion The release of HMGB1 induced by IR can cause hepatic cell damage probably by stimulating P38 MAPK signaling pathway. Key words: Ischemia-reperfusion; Hepatocyte; Protein kinases, P38 MAPK; High mobility group, HMGB1