福建中医药2025，Vol.56Issue(4)：16-23,8.DOI:10.13260/j.cnki.jfjtcm.2025.04004
基于Nrf2/HO-1信号通路探究清解扶正颗粒对奥沙利铂导致小鼠肝损伤的疗效及作用机制
Efficacy and Mechanism of Qingjie Fuzheng Granule on Liver Damage Induced by Oxaliplatin in Mice Based on the Nrf2/HO-1 Signaling Pathway
摘要
Abstract
Objective:To observe the therapeutic effect of Qingjie Fuzheng Granule(QFG)on a murine model of oxaliplatin(OXA)-induced liver injury and elucidate the underlying mechanisms,potentially offering a novel theoretical foundation for clinical application.Methods:A total of 18 healthy male BALB/c mice aged 3 to 5 weeks were divided into the control,model(OXA)and treatment(OXA+QFG)groups with 6 mice in each group according to random number table method.The OXA and OXA+QFG groups received intraperitoneal injections of a 1 mg/mL OXA solution at a volume of 10 mL/kg based on body weight of mice,while the con-trol group received an equivalent volume of sterile normal saline.Injections were administered once a week for 4 weeks to establish the the liver injury model.At the same time,the OXA+QFG group received gastric lavage with a 125 mg/mL QFG solution at a vol-ume of 8 mL/kg based on body weight of mice.Both the control and OXA groups received gastric lavage with the same volume of sterile normal saline.These treatments were administered once a day for 4 weeks.After the intervention,changes in body mass in 3 groups were detected,the liver tissue morphology and lipid droplet changes were observed by hematoxylin-eosin(HE)and oil red O staining.Biochemical methods were used to measure the contents of malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT),triglyceride(TG),total cholesterol(TC),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in liver tissue.The contents of ALT and AST in serum were also detected.The content of reactive oxygen species(ROS)in liver was detected by flow cytometry.The mRNA transcription levels of Nrf2,HO-1 and Keap1 in the Nrf2/HO-1 signaling pathway were analyzed by RT-qPCR.Western blot and immunofluorescence were used to evaluate the relative protein expression.Results:Compared with the con-trol group,the OXA group showed a significant decrease in body mass(P<0.05),disruption of liver lobule structure,and increased lip-id droplets in hepatocytes.The contents of MDA,TG,TC and ROS in liver tissues increased(P<0.05),the contents of SOD and CAT in liver tissues decreased(P<0.05),and the contents of ALT and AST in liver and serum increased(P<0.05),the mRNA transcription levels,relative protein expressions and fluorescence intensity of Nrf2 and HO-1 decreased(P<0.05),while the mRNA transcription level,relative protein expression and fluorescence intensity of Keap1 increased(P<0.05).Compared with the OXA group,the changes of body mass in OXA+QFG group had no statistical significance(P>0.05),but the morphological damage of liver tissue alleviated,the number of lipid droplets in liver tissue decreased,the contents of MDA,TG,TC and ROS in liver tissue decreased(P<0.05),and the content of SOD and CAT in liver tissue increased(P<0.05),ALT and AST contents in liver tissue and serum decreased(P<0.05),the mRNA transcription levels,relative protein expressions and fluorescence intensity of Nrf2 and HO-1 increased(P<0.05),the mRNA transcription level,relative protein expressions and fluorescence intensity of Keap1 decreased(P<0.05).Conclusion:QFG may exert a protective effect on oxaliplatin-induced liver injury by modulating oxidative stress levels and activating the Nrf2/HO-1 signaling pathway,thereby improving oxaliplatin-induced liver injury.关键词
肝损伤/清解扶正颗粒/奥沙利铂/氧化应激/Nrf2/HO-1信号通路Key words
liver injury/Qingjie Fuzheng Granule/oxaliplatin/oxidative stress/Nrf2/HO-1 signaling pathway引用本文复制引用
叶丽芳,贾沛芝,刘锦洪,林久茂..基于Nrf2/HO-1信号通路探究清解扶正颗粒对奥沙利铂导致小鼠肝损伤的疗效及作用机制[J].福建中医药,2025,56(4):16-23,8.基金项目
福建省自然科学基金项目(2022J01368) （2022J01368）
