钩藤碱对APAP诱导的药物性肝损伤的保护作用及对Nrf2/HO-1/NF-κB信号通路的影响OA

Objective:To investigate protective effect of Rhynchophylline on acetaminophen(APAP)-induced acute liver injury(ALI)in mice based on Nrf2/HO-1/NF-κB signaling pathway.Methods:ALI model was established by intraperitoneal injection of APAP 400 mg/kg-in mice.Experimental mice were divided into blank group,model group,positive drug group(N-acetylcysteine,200 mg/kg),low,medium and high-dose Rhynchophylline groups(2,4,8 mg/kg).Activities of ALT,AST and ALP in serum were detected by an automatic biochemical analyzer.TNF-α,IL-6 and IL-1β levels in mouse serum were detected by ELISA.HE and TUNEL staining were used to observe pathological structure and apoptosis of liver.SOD,MDA and GSH-Px levels in liver tissue were measured by kits.Nrf2/HO-1/NF-κB p65 signaling pathway-related protein and mRNA expressions were detected by Western blot and RT-PCR.Nrf2 knockdown was performed using Nrf2 siRNA in AML12 cells,MDA and IL-6 levels in normal and Nrf2 knockout cells were measured.Results:Compared with model group,after Rhynchophylline treatment,activities of AST,ALT,ALP,TNF-α,IL-6 and IL-1β were reduced(P<0.05,P<0.01);liver structure of mice tended to be normal,and number of apoptotic cells were signifi-cantly decreased;MDA content was induced,SOD and GSH-Px contents were increased(P<0.05,P<0.01).Moreover,it promoted expressions of Nrf2,HO-1,IκBα protein and Nrf2,HO-1 mRNA,and inhibited expressions of p-NF-κB p65,p-IκBα protein and NF-κB p65 mRNA(P<0.05,P<0.01).Furthermore,compared with normal AML12 cells,effects of Rhynchophylline on reducing MDA and IL-6 levels were significantly inhibited after Nrf2 knockdown.Conclusion:Rhynchophylline has preventive effects on APAP-induced ALI,whose mechanism may be related to regulation of Nrf2/HO-1/NF-κB signaling pathway.