Effect of metformin on liver injury induced by intestinal ischemia-reperfusion in mice and its relationship with Akt
Objective:To evaluate the effect of metformin on liver injury induced by intestinal ischemia-re-perfusion in mice and its relationship with protein kinase B(Akt).Methods:Twenty-four SPF-grade healthy male C57BL/6 mice were randomly divided into four groups(n=6):sham operation group(S group),intestinal ischemia-reperfusion group(I/R group),metformin+ischemia-reperfusion group(M group),and metformin+ischemia-reperfusion+protein kinase B inhibitor Triciribine(TCN)group(MT group).The mouse model of intestinal ischemia-reperfusion injury was established by clamping the superior mesenteric artery for 45 minutes followed by reperfusion for 120 minutes.Orbital venous blood samples were collected at the end of reperfusion for determination of serum alanine aminotrans-ferase(ALT)and aspartate aminotransferase(AST)levels,then the mice were sacrificed,and liver tissue samples were obtained for microscope examination of the pathological changes and determina-tion of glutathione(GSH)activity,malondialdehyde(MDA)content,the expression of interleukin-6(IL-6)mRNA(by fluorescence quantitative polymerase chain reaction),the expression of protein ki-nase B(Akt)and its phosphorylated protein(p-Akt),glutathione peroxidase 4(GPX4),and Acly-CoA synthetase long-chain family 4(ACSL4)(by Western Blot).The degree of liver injury was assessed using the Eckhoff scoring method.Results:Compared with those in the S group,the Eckhoff score,serum ALT and AST levels increased,GSH activity decreased,MDA content increased,the expres-sion of IL-6 mRNA was up-regulated(P<0.05),the expression of GPX4 was down-regulated,and the expression of p-Akt and ACSL4 were up-regulated in the I/R group(P<0.05).Compared with those in the I/R group,the Eckhoff score,serum ALT and AST levels decreased,GSH activity in-creased,MDA content decreased,the expression of IL-6 mRNA was down-regulated(P<0.05),the expression of GPX4 and p-Akt were up-regulated,and the expression of ACSL4 was down-regulated in M group(P<0.05).Compared with those in the M group,the Eckhoff score,serum ALT and AST levels increased,GSH activity decreased,MDA content increased,the expression of IL-6 mRNA was up-regulated,the expression of GPX4 was down-regulated,and the expression of p-Akt and ACSL4 were up-regulated in the MT group(P<0.05).Conclusion:Metformin exerts a protec-tive effect on liver injury induced by intestinal ischemia-reperfusion in mice by inhibiting ferroptosis,and the mechanism may be related to the activation of Akt.
MetforminFerroptosisIntestinal Ischemia-ReperfusionLiver InjuryProtein Kinase B
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