苦参碱对伴刀豆球蛋白A诱导的免疫性肝损伤的保护作用及潜在机制研究OA

Objective:To explore the protective effects of matrine on ConA-induced immune liver injury and underlying mechanism,thus providing an alternative drug for the treatment of autoimmune hepatitis(AIH).Methods:Immune liver injury model was established by ConA.After pretreatment with matrine,the transaminase activities were detected using AST and ALT assay kits.H&E staining was used to assess tissue pathological damage.The oxidative stress levels were detected by malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT),and total antioxidant capacity(TAC)assay kits.The infiltration of CD4+T cells and macrophages were evaluated by immunofluorescence staining.The inflammatory cytokine levels were measured by ELISA.TUNEL staining was used to assess the hepatocyte apoptosis.Western blot was used to analyze the expression and phosphorylation levels of key proteins in the JAK1/STAT3 and PI3K/Akt signaling pathways.Results:Matrine could reduce AST and ALT levels in plasma,and alleviate hepatocyte apoptosis/necrosis and inflammatory infiltration.Meanwhile,matrine could inhibit the infiltration of CD4+T cells and macrophages in the liver,and reduce the expression of inflammatory factors.In addition,matrine could increase the activities of SOD and CAT in the liver and decrease MDA content,thereby improving TAC level.Western blot results showed that matrine could inhibit JAK1 expression and STAT3 phosphorylation,while promoting PI3K expression and Akt phosphorylation.Conclusion:Matrine can inhibit ConA-induced inflammatory responses and oxidative stress,and alleviate hepatocyte apoptosis by regulating the JAK1/STAT3 and PI3K/Akt pathways.It can serve as a natural candidate for the development of drugs for AIH treatment.