槲皮素通过抑制TGF-β/TAK1/JNK和TGF-β/Smad2信号通路发挥抗肝纤维化的作用  

Effect of quercetin on liver fibrosis by inhibiting TGF-β/TAK1/JNK and TGF-β/Smad2 signaling pathways

作　　者：王绍展[1] 王媛媛[1] 顾妍秋 陈春 李胜男[1] 王蓉[1] 原永芳[1] WANG Shao-zhan;WANG Yuan-yuan;GU Yan-qiu;CHEN Chun;LI Sheng-nan;WANG Rong;YUAN Yong-fang(Department of Pharmacy,Shanghai 9th People’s Hospital,School of Medicine,Shanghai Jiao Tong University,Shanghai 201999)

机构地区：[1]上海交通大学医学院附属第九人民医院药剂科,上海201999

出　　处：《中南药学》2022年第5期965-972,共8页Central South Pharmacy

基　　金：国家自然科学基金项目(No.81703779,No.81803815)。

摘　　要：目的探讨槲皮素抗肝纤维化的潜在作用机制。方法通过腹腔注射10 mg·kg^(-1)二甲基亚硝胺构建大鼠肝纤维化模型,于造模第3周开始灌胃槲皮素(12.5、25、50 mg·kg^(-1))治疗,造模第4周末处死;对肝组织进行HE和胶原染色,检测羟脯氨酸含量;检测肝功能指标和肝纤维化指标的变化;实时定量PCR检测肝星状细胞活化相关因子的表达水平;免疫组织化学法测定肝组织中TGF-β/TAK1/JNK和TGF-β/Smad2信号途径相关蛋白表达水平的变化。采用MTT法和Western blot法检测槲皮素对大鼠肝星状细胞系HSC-T6的增殖的影响以及对TGF-β1诱导的TAK1、JNK、Smad2蛋白磷酸化的抑制作用。结果与模型组相比,槲皮素25和50 mg·kg^(-1)组大鼠肝纤维化程度明显降低;槲皮素(20和40μmol·L^(-1))能显著抑制HSC-T6细胞的增殖,并能有效地降低TGF-β/TAK1/JNK和TGF-β/Smad2信号途径相关蛋白磷酸化程度。结论槲皮素可通过调节TGF-β/TAK1/JNK和TGF-β/Smad2信号通路影响肝星状细胞活化以发挥抗肝纤维化作用。Objective To determine the potential mechanism of quercetin on liver fibrosis.Methods The SD rat model of liver fibrosis was established by intraperitoneal injection of 10 mg·kg^(-1)dimethylnitrosamine.Quercetin(12.5,25,and 50 mg·kg^(-1))was intragastrically used at the third week for 2 weeks.The mRNA levels of the liver were detected by real-time PCR,and the protein expression of TGF-β/TAK1/JNK and TGF-β/Smad2 signaling pathways were determined by immunohistochemistry.The proliferation activity of HSC-T6 cells,the mRNA levels and protein expressing about fibrosis-indexs in HSC-T6 cells were determined by MTT,real-time PCR and Western blot,respectively.Results The quercetin groups(25 and 50 mg·kg^(-1))effectively attenuated the progress of liver fibrosis in the rats.Quercetin(20 and 40μmol·L^(-1))significantly inhibited the activation of HSC-T6 cells,and decreased the phosphorylation of TGF-β/TAK1/JNK and TGF-β/Smad2 signaling pathways.Conclusion Quercetin has significant effect on liver fibrosis,whose mechanism may relate to inhibition of the activation of hepatic stellate cells by regulating TGF-β/TAK1/JNK and TGF-β/Smad2 signaling pathways.

关 键 词：肝纤维化 槲皮素 肝星状细胞 TGF-β/TAK1/JNK信号通路 TGF-β/Smad2信号通路 

分 类 号：R285[医药卫生—中药学]