中成药2025，Vol.47Issue(5)：1477-1486,10.DOI:10.3969/j.issn.1001-1528.2025.05.010
基于NF-κB/TGF-β1信号通路探讨大黄灵仙方对胆汁淤积性肝纤维化大鼠Th1/Th2细胞免疫失衡的调节作用
Regulatory effects of Dahuang Lingxian Recipe on Th1/Th2 cell immune imbalance in a rat model of cholestatic liver fibrosis via NF-κB/TGF-β1 signaling pathway
摘要
Abstract
AIM To explore the effects of Dahuang Lingxian Recipe on Th1/Th2 cell immune imbalance in a rat model of cholestatic liver fibrosis(CLF).METHODS 20 SD rats were randomly divided into the normal group,the model group,the ursodeoxycholic acid group(0.063 g/kg)and the Dahuang Lingxian Recipe group(4.8 g/kg),with 5 rats in each group.Except for those of the normal group,the rats of all other groups had open surgery of common bile duct ligation,followed by the gavage of corresponding drug two days later,and the procurement of the samples after gavage in the third week.The rats had their degree of liver fibrosis observed by HE and Masson stainings;their levels of serum total bile acid(TBA),alkaline phosphatase(AKP),γ-glutamyltransferase(γ-GT),alanine aminotransferase(ALT),aspartate aminotransferase(AST)and total bilirubin(TBil)measured by the kit;their hepatic percentage of TGF-β1,p-Smad2 and p-Smad3 positive cells detected by immunofluorescence and immunohistochemical staining;their.hepatic expressions of TGF-β1,Smad4,NF-κB p65,Collagen Ⅰ and Collagen Ⅲ protein and mRNA detected by Western blot and RT-qPCR;their levels of helper T cell 1(Th1)and helper T cell 2(Th2)in peripheral blood detected by flow cytometry,and their ratio of Th1/Th2 calculated as well.RESULTS Compared with the model group,the groups intervened with either ursodeoxycholic acid or Dahuang Lingxian Recipe displayed well-ordered liver cells,hepatic lobules and hepatic cords;a small amount of fatty degeneration;significantly reduced connective hyperplasia of hepatic fibers;significantly narrowed fibrous cords;a small amount of blue fibrous septa;greatly improved pathological injuries including inflammatory infiltration of central vein and portal area;decreased levels of serum TBA,TBil,AKP,γ-GT,ALT and AST(P＜0.05);decreased hepatic expressions of TGF-β1,p-Smad2 and p-Smad3(P＜0.05);decreased hepatic expressions of TGF-β1,Smad4,NF-κB p65,Collagen Ⅰ and Collagen Ⅲ protein and mRNA(P＜0.05);and increased counts of Th1 cells in peripheral blood,decreased counts of Th2 cells,resultsing increased Th1/Th2 ratio(P＜0.05).And an even better effect was observed in the Dahuang Lingxian Recipe group.CONCLUSION Dahuang Lingxian Recipe can reduce or reverse CLF by inhibiting hepatic stellate cell activation through maintaining Th1/Th2 cell immune balance via the NF-κB/TGF-β1 signaling pathway.关键词
大黄灵仙方/胆汁淤积性肝纤维化/NF-κB/TGF-β1信号通路/Th1/Th2细胞/免疫平衡Key words
Dahuang Lingxian Recipe/cholestatic liver fibrosis/NF-κB/TGF-β1 signaling pathway/Th1/Th2 cells/immunologic balance分类
中医学引用本文复制引用
宁曹,庞浇安,谭熙,罗艳萍,韦慧怡,黄波,王家冠..基于NF-κB/TGF-β1信号通路探讨大黄灵仙方对胆汁淤积性肝纤维化大鼠Th1/Th2细胞免疫失衡的调节作用[J].中成药,2025,47(5):1477-1486,10.基金项目
广西高校中青年教师科研基础能力项目(2022KY1668) （2022KY1668）
广西中医药大学校级科研项目青年基金项目(2023MS022,2023QN008) （2023MS022,2023QN008）
广西中医药大研究生教育创新计划项目(YCSY2023035) （YCSY2023035）
广西中医药大学第一附属医院院级科研项目(2021QN001) （2021QN001）
