槐角苷通过促进AMPK激活抑制肝脏缺血再灌注损伤

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【中图分类号】R285.5 【文献标识码】A

【Abstract】 Objective To investigate the protective effect of the natural compound sophoricoside （SOP） against hepatic ischemia-reperfusion injury （HIRI） and its underlying molecular mechanism，providing evidence for the development of HIRI therapeutics.Methods An in vitro hypoxia/reoxygenation （H/R） model in hepatocytes and an in vivo mouse hepatic ischemiareperfusion injury （HIRI） model were established. In vitro，cell viability was assessed by CCK-8 assy， while inflammatory cytokines and related proteins were analyzed using RT-qPCR and Western blot （WB）.In mice， serum alanine aminotransferase （ALT）and aspartate aminotransferase （AST）activities were measured.Hepatic pathological damage and apoptosis were evaluated by H&E staining and immunofluorescence staining. Molecular docking predicted the interaction between SOP and AMP-activated protein kinase （AMPK）， which was then validated using the AMPK inhibitor Compound C.Results SOP significantly enhanced hepatocyte viability and suppressed inflammatory cytokine production under H/R conditions in vitro.In mice， SOP reduced serum ALT and AST levels，allviated hepatic inflammation，and decreased apoptosis.Mechanistic studies indicated that， SOP promoted AMPK phosphorylation in both in vitro and in vivo. Molecular docking indicated stable binding of SOP to AMPK through hydrogen bonding. The protective efects of SOP were reversed by AMPK inhibition， confirming AMPK as a critical target of SOP action. Conclusion SOP exerts a protective effct against HIRI by targeting and activating AMPK to inhibit inflammation and apoptosis， providing a new strategy for natural product-based drug development and targeted therapy for HIRI

【Keywords】Hepatic ischemia-reperfusion injury; Sophoricoside; AMP-activated protein kinase Inflammation; Apoptosis

肝脏缺血-再灌注损伤（hepatic ischemiareperfusioninjury，HIRI）是部分肝切除与肝移植术中常见的病理生理现象，其机制为缺血器官因血液供应不足导致缺氧、细胞代谢紊乱，而血流恢复后氧与营养供应仍不足，同时伴随代谢副产物蓄积[]。（剩余19872字）