人参皂苷Rb2通过激活Keap1-Nrf2/HO-1信号通路改善对乙酰氨基酚诱导的肝损伤OA

Aim To investigate the protective effect of ginsenoside Rb2(Rb2)against acetaminophen(APAP)-induced liver injury and its underlying mo-lecular mechanism.Methods A model of APAP-induced liver injury was constructed by using C57BL/6J mice and AML-12 cells.Serum levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)were measured.Pathological changes in mouse liver tissues were assessed by HE staining and F4/80 immunohistochemical staining.The contents of inter-leukin-1β(IL-1β),IL-6,and tumor necrosis factor α(TNF-α)in the serum of mice and the supernatant of AML-12 cells were detected by ELISA.Superoxide dismutase(SOD),glutathione(GSH)and malondial-dehyde(MDA)levels were detected in liver tissues and AML-12 cells by biochemical methods.The ex-pression levels of Keap1,Nrf2,and HO-1 were de-tected by Western blot and RT-qPCR.The importance of Nrf2 and HO-1 in the hepatoprotective effect of Rb2 was verified by using ML385(Nrf2 inhibitor)and SnPP(HO-1 inhibitor).Results Rb2 reduced the levels of ALT and AST in the serum of APAP-induced mice,improved liver injury in mice,and decreased the levels of IL-1β,IL-6 and TNF-α in the serum of mice and the supernatant of AML-12 cells.Compared with the model group,the levels of MDA in liver tis-sues and AML-12 cells decreased,while GSH and SOD levels increased in the Rb2 administration group.Western blot and RT-qPCR results indicated that Rb2 was involved in the regulation of the Keap1-Nrf2/HO-1 signaling pathway.Conclusion Rb2 inhibits APAP-induced inflammatory response and oxidative stress through the Keap1-Nrf2/HO-1 signaling pathway,and has an ameliorative effect on APAP-induced liver in-jury.