白藜芦醇通过Nrf2/Keap1途径减轻类风湿关节炎肝脏炎症和氧化应激  

Resveratrol attenuates hepatic inflammation and oxidative stress in rheumatoid arthritis via Nrf2/Keap1 pathway

作　　者：范学菲 周剑[2] 陈苏环 张梦妍 刘浩淼 苏蕊[3] 陈广祎 邵玉宝 姚涛 陈晓宇[1] FAN Xue-fei;ZHOU Jian;CHEN Su-huan;ZHANG Meng-yan;LIU Hao-miao;SU Rui;CHEN Guang-yi;SHAO Yu-bao;YAO Tao;CHEN Xiao-yu(Dept of Histology and Embryology,Anhui Medical University,Hefei 230032,China;Dept of Orthopedics,the First Affiliated Hospital Anhui Medical University,Hefei 230088,China;Clinical Medical College,Anhui Medical University,Hefei 230032,China;Microscopic Morphological Center Lab,Anhui Medical University,Hefei 230032,China;Dept of Orthopedics,the Third Affiliated Hospital Anhui Medical University,Hefei 230061,China)

机构地区：[1]安徽医科大学组织胚胎学教研室,安徽合肥230032 [2]安徽医科大学第一附属医院骨科,安徽合肥230088 [3]安徽医科大学临床医学系,安徽合肥230032 [4]安徽医科大学形态学实验中心,安徽合肥230032 [5]安徽医科大学第三附属医院骨科,安徽合肥230061

出　　处：《中国药理学通报》2025年第5期861-867,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81373421);安徽医科大学第三附属医院基础与临床合作研究提升计划培育专项(No 2022sfy010);安徽医科大学“早期接触科研”项目(No 2024-ZQKY-078,2023-ZQKY-093);安徽省自然科学基金项目(No 2208085MH212)。

摘　　要：目的探讨白藜芦醇(resveratrol,Res)对类风湿关节炎(rheumatoid arthritis,RA)肝脏炎症和氧化应激的治疗作用,并阐明Nrf2/Keap1信号通路在其中的调控机制关系。方法采用鸡Ⅱ型胶原联合完全弗氏佐剂诱导关节炎小鼠模型,通过管饲法予Res处理。检测小鼠血清肝功能指标和肝脏炎症和氧化应激水平。使用TNF-α(5μg·L^(-1))处理小鼠原代肝细胞(MPHs)建立肝脏炎症和氧化应激体外细胞模型,CCK-8检测细胞增殖抑制率,蛋白质印迹法检测炎症和氧化应激相关指标。通过使用Nrf2抑制剂和Keap1过表达质粒处理MPHs,探究Res减轻类风湿关节炎肝脏炎症和氧化应激的内在机制。结果Res明显降低胶原诱导型关节炎小鼠肝组织以及经TNF-α处理的MPHs的炎症和氧化应激水平,并且激活了Nrf2/Keap1信号通路。使用Nrf2抑制剂和Keap1的过表达加剧了MPHs炎症和氧化应激水平,促进细胞凋亡。结论Res通过Nrf2/Keap1途径减轻类风湿关节炎肝脏炎症和氧化应激。Aim To explore the therapeutic effects of resveratrol(Res)on hepatic inflammation and oxidative stress in rheumatoid arthritis(RA),and to elucidate the relationship of the regulatory mechanism of the Nrf2/Keap1 signaling pathway in it.Methods A mouse model of arthritis was induced using chicken typeⅡcollagen in combination with complete Freund’s adjuvant,and Res was administered by tube feeding for treatment.Serum liver function indices and levels of hepatic inflammation and oxidative stress were detected in mice.An in vitro cellular model of hepatic inflammation and oxidative stress was established by treating mouse primary hepatocytes(MPHs)with TNF-α(5μg·L^(-1)),cell proliferation inhibition was detected by CCK-8,and inflammation and oxidative stress-related indices were detected by protein blotting.The intrinsic mechanisms by which Res attenuated hepatic inflammation and oxidative stress in rheumatoid arthritis were explored by treating MPHs with Nrf2 inhibitor and Keap1 overexpression plasmid.Results Res significantly reduced the levels of inflammation and oxidative stress in hepatic tissues of collagen-induced arthritis mice as well as TNF-α-treated MPHs,and activated the Nrf2/Keap1 signaling pathway.Inflammation and oxidative stress levels in MPHs were exacerbated by the use of Nrf2 inhibitors and Keap1 overexpression,which promoted apoptosis.Conclusion Res attenuates hepatic inflammation and oxidative stress in rheumatoid arthritis via the Nrf2/Keap1 pathway.

关 键 词：类风湿关节炎 肝损伤 白藜芦醇 炎症 氧化应激 Nrf2/Keap1 

分 类 号：R-332[医药卫生] R284.1R349.1R364.5R575.1R593.22