时珍国医国药2025，Vol.36Issue(10)：1838-1847,10.DOI:10.70976/j.1008-0805.SZGYGY-2025-1006
黄芪-地龙调节pJNK/pSTAT3/pFOXO1氧化应激通路干预肺纤维化的机制研究
Study on the mechanism of Huangqi-Dilong in intervening pulmonary fibrosis through p-JNK/p-STAT3/p-FOXO1-mediated oxidative stress signaling pathway
摘要
Abstract
Objective To verify the action mechanism of Huangqi(Astragali Radix)-Dilong(earthworm)paired medicine in the treat-ment of pulmonary fibrosis(PF).Methods Active ingredients of Huangqi-Dilong were collected from traditional Chinese medicine da-tabases and the disease targets for PF from disease target databases.The intersection targets were subjected to GO functional and KEGG pathway enrichment analysis.The potential targets of FOXO signal pathway were selected to dock with the main active components,and an animal model was made to verify it.C57BL/6 male mice were randomly divided into the normal group(n=10),the model group(n=10),the treatment group(n=10)and the positive control group(n=10)to establish the PF model by endotracheal infusion of bleo-mycin(BLM).The lung tissues of mice in each group were stained with HE and Masson,and the levels of serum inflammatory factors,hydroxyproline(HYP)and oxidative stress were detected by ELISA and UV/spectrophotometry.The expressions of ROS and mitochon-drial membrane potential were detected by flow cytometry,and the protein expressions of FOXO1/p-FOXO1,JNK/p-JNK and STAT3/p-STAT3 were detected by Western blot(WB).Results Through data analysis,a total of 60 active chemical components of Huangqi-Dilong were screened.The main target proteins in the potential signaling pathway FOXO include FOXO,JNK,STAT3,and MST1.The results of molecular docking experiments showed that a variety of active chemical components in the paired medicine could bind well to the above targets.The animal experiments showed that the mice model of PF was successfully induced by intratracheal instil-lation of BLM,destruction of lung tissue structure and infiltration of inflammatory cells.Masson staining showed that there were typical characteristics of PF.After treatment with Huangqi-Dilong,the damage of pulmonary structure and the characteristics of PF were allevi-ated.ELISA results showed that Huangqi-Dilong could significantly alleviate oxidative stress injury,decrease MDA levels,and increase SOD and POD expressions,and ATP synthase activity and ATP content were increased.WB assay showed that the levels of p-JNK/p-STAT3/p-FOXO1 in the treatment group were decreased.Conclusion Huangqi-Dilong relieves FOXO1 inactivation by regulating the p-JNK/p-STAT3/p-FOXO 1 signaling pathway,exerting anti-oxidative stress,improving mitochondrial function,decreasing inflam-matory response,and inhibiting extracellular matrix deposition,thereby treating PF.关键词
黄芪-地龙/肺纤维化/p-JNK/p-STAT3/p-FOXO1/氧化应激Key words
Huangqi-Dilong paired medicine/Pulmonary fibrosis/p-JNK/p-STAT3/p-FOXO1/Oxidative stress分类
医药卫生引用本文复制引用
胡艾悦,张珍珍,胡诗维,刘珊,柯孟婷,夏慧,陈龙云,陈会敏..黄芪-地龙调节pJNK/pSTAT3/pFOXO1氧化应激通路干预肺纤维化的机制研究[J].时珍国医国药,2025,36(10):1838-1847,10.基金项目
湖北省自然科学联合发展基金重点项目(2024AFD258) （2024AFD258）
