摘要
目的探讨芹黄素(apigenin,API)对肝纤维化模型小鼠的抗纤维化作用及其机制。方法C57小鼠每周2次用四氯化碳(CCl_(4))灌胃,连续12周,从第5周开始,每天给药API(10、20或40 mg·kg^(-1))。小鼠随机分为6组(每组6只):对照组、CCl_(4)组、CCl_(4)+Colchicine(秋水仙碱,0.2 mg·kg^(-1))组、CCl_(4)+API(10 mg·kg^(-1))组、CCl_(4)+API(20 mg·kg^(-1))组和CCl_(4)+API(40 mg·kg^(-1))组。评估小鼠肝功能、组织病理学以及肝组织纤维化的血清标志物,并测定炎症因子和NF-κB/TGF-β/Smad通路蛋白的表达情况。结果API可显著改善CCl_(4)诱导的小鼠肝损伤,包括转氨酶[谷丙转氨酶(ALT)、谷草转氨酶(AST)]活性降低和病理改变。API抑制α-SMA、Vimentin和Desmin的表达。API逆转了CCl_(4)诱导的p-P65/P65比值升高、IκB降解以及促炎细胞因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死子因子-α(TNF-α)的升高,显著下调TGF-β1和p-Smad3的表达。结论API通过调节NF-κB/TGF-β/Smad通路抑制炎症和ECM沉积,从而减轻小鼠肝纤维化。
Objective To investigate the anti-fibrotic effect and mechanism of apigenin(API)in a mouse model of liver fibrosis.Methods C57 mice were intragastrically administered with carbon tetrachloride(CCl_(4))twice a week for 12 consecutive weeks.From the 5th week,API(10,20,or 40 mg·kg^(-1))was administered daily.The mice were randomly divided into 6 groups(6 mice in each group):the control group,the CCl_(4)group,the CCl_(4)+Colchicine(0.2 mg·kg^(-1))group,the CCl_(4)+API(10 mg·kg^(-1))group,the CCl_(4)+API(20 mg·kg^(-1))group,and the CCl_(4)+API(40 mg·kg^(-1))group.The liver function,histopathology,and serum markers of liver tissue fibrosis in the mice were evaluated,and the expressions of inflammatory factors and proteins in the NF-κB/TGF-β/Smad pathway were determined.Results API significantly improved CCl_(4)-induced liver injury in mice,including a decrease in the activities of transaminases[alanine aminotransferase(ALT)and aspartate aminotransferase(AST)]and pathological changes.API inhibited the expressions ofα-SMA,Vimentin,and Desmin.API reversed the increase in the p-P65/P65 ratio,the degradation of IκB,and the elevation of pro-inflammatory cytokines interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)induced by CCl_(4),and significantly down-regulated the expressions of TGF-β1 and p-Smad3.Conclusion API alleviates liver fibrosis by regulating the NF-κB/TGF-β/Smad pathway to inhibit inflammation and extracellular matrix(ECM)deposition.
作者
李晓英
李宁宁
李赛菲
刘湘花
孙韬
LI Xiaoying;LI Ningning;LI Saifei;LIU Xianghua;SUN Tao(Department of Basic Medicine,Henan Medical College,Zhengzhou Henan 451191,China;Medical Research Experimental Center,Henan Medical College,Zhengzhou Henan 451191,China;School of Traditional Chinese Medicine,Henan University of Chinese Medicine,Zhengzhou Henan 450046,China)
出处
《河南医学高等专科学校学报》
2025年第2期128-135,共8页
Journal of Henan Medical College
基金
河南省科技攻关项目(222102310373,242102310250)
河南省高等学校重点科研计划项目(22B360003)。
