Stachydrine Activates the AMPK/SIRT1 Signaling Pathway to Promote Autophagy and Alleviate Sepsis-induced Acute Kidney Injury
Objective:To investigate the role and potential mechanism of STA in sepsis-induced acute kidney injury(AKI),and to provide new ideas for clinical treatment.Methods:At the cellular level,HEK293 cells were treated with lipopolysac-charide(LPS)and STA.Detected the level of ROS,inflammatory factors tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1 β),interleukin-6(IL-6),and autophagy markers LC3B Ⅱ and LC3B The protein levels of p-AMPKα/AMPKα and SIRT1 were detected.At the animal level,C57BL/6 male mice were intraperitoneally injected with LPS to establish a sepsis induced AKI model.The treatment group was given STA 30 mg/kg daily by gavage from 7 days before LPS injection.Hematoxylin-eosin(HE)staining,Western blotting,and RT-qPCR were used to detect the levels of inflammatory factors,autophagy markers,and ac-tivation of AMPK/SIRT1 signaling pathway in kidney tissue.Results:At the cellular level,ROS was significantly increased in HEK293 cells after LPS treatment,the levels of inflammatory factors TNF-α,IL-1β and IL-6 were significantly increased,the LC3B Ⅱ/LC3B Ⅰ ratio was decreased,p62 protein level was up-regulated,and p-AMPKα and SIRT1 protein levels were de-creased(P＜0.05).STA treatment significantly reduced LPS-induced ROS and inflammatory cytokines levels,increased LC3B Ⅱ/LC3B Ⅰ ratio,decreased p62 level,and increased p-AMPKα and SIRT1 expression levels(P＜0.05).At the animal level,West-ern blot and RT-qPCR results showed that the levels of inflammatory factors TNFα,IL-1β and IL-6 were increased,the protein levels of LC3B Ⅱ/LC3B Ⅰ,p-AMPKα/AMPKα and SIRT1 were decreased,and the level of p62 was increased in the kidney tissue of mice induced by LPS.The STA+LPS group had significantly decreased expression of inflammatory factors in kidney tissue,signifi-cantly increased expression of LC3BⅡ/LC3B Ⅰ,p-AMPKα/AMPKα,and SIRT1,and a significantly decreased expression of p62(P＜0.05).Conclusion:STA can alleviate sepsis-induced acute kidney injury by activating AMPK/SIRT1 signaling pathway to promote autophagy.
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维普
