湖南中医药大学学报2025，Vol.45Issue(11)：2063-2071,9.DOI:10.3969/j.issn.1674-070X.2025.11.006
基于"肝病实脾"理论探讨黄连温胆汤通过修复肠屏障及抑制TLR4/NF-κB通路抗肝纤维化的作用机制
Mechanism of action of Huanglian Wendan Decoction against hepatic fibrosis via intestinal barrier repair and inhibition of TLR4/NF-κB pathway based on the theory of"fortifying the spleen to treat liver disease"
摘要
Abstract
Objective To investigate the mechanism of action of Huanglian Wendan Decoction(HLWDD)in repairing the intestinal mucosal barrier and ameliorating hepatic fibrosis(HF)based on the TCM theory of"fortifying the spleen to treat liver disease".Methods SD rats were randomly divided into four groups using a random number table method:the control group,model group,colchicine group,and HLWDD group,with eight rats in each group.Except the blank group,the other three groups were induced to develop liver fibrosis models using 40%carbon tetrachloride(CCl4),with injections administered once every 3 days for a duration of eight weeks.At week 5 of modelling,the HLWDD group was gavaged with HLWDD at a dose of 12 g/kg,the colchicine group was gavaged with a colchicine solution at a dose of 0.2 mg/kg,while the blank and model groups were gavaged with physiological saline solution once daily for 8 weeks.HE and Masson staining were used to evaluate the histopathological changes in hepatic and intestinal tissues.ELISA was employed to measure the levels of tumor necrosis factor-α(TNF-α)and lipopolysaccharide(LPS)in the serum.Western blot was performed to determine the protein expression levels of α-smooth muscle actin(α-SMA)and collagen type I(CollagenⅠ)in hepatic tissues,as well as Occludin,zonula occludens-1(ZO-1),Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),and nuclear factor-κB(NF-κB)p65 in intestinal tissues.Results Compared with the blank group,the model group exhibited severe hepatic damage as demonstrated by HE staining of hepatic tissues;Masson staining revealed typical fibrosis with an increased collagen fiber area ratio(P＜0.01).Protein expression levels of CollagenⅠ and α-SMA in hepatic tissues were elevated(P＜0.01).HE staining of intestinal tissues revealed severe mucosal structural damage,accompanied by decreased protein expression levels of Occludin and ZO-1(P＜0.01)and increased protein expression levels of TLR4,MyD88,and NF-κB p65 in intestinal tissues(P＜0.05,P＜0.01).Serum levels of TNF-α and LPS were significantly elevated(P＜0.01).Compared with the model group,both the HLWDD and colchicine groups showed alleviated hepatic damage in HE staining,improved fibrosis degree in Masson staining,and significantly reduced collagen fiber area ratio(P＜0.01).Protein expression levels of CollagenⅠ and α-SMA in hepatic tissues decreased(P＜0.05,P＜0.01).The HLWDD group demonstrated significant restoration of the intestinal mucosal structure in HE staining,increased protein expression levels of Occludin and ZO-1(P＜0.01),decreased protein expression levels of TLR4,MyD88,and NF-κB p65(P＜0.05,P＜0.01),and reduced serum levels of TNF-α and LPS(P＜0.01).The colchicine group showed decreased serum TNF-α level(P＜0.01).Compared with the colchicine group,the HLWDD group exhibited higher protein expression levels of Occludin and ZO-1(P＜0.05,P＜0.01)while lower protein expression levels of TLR4 and MyD88(P＜0.01)in intestinal tissues,as well as reduced LPS levels in serum(P＜0.01).Conclusion HLWDD ameliorates HF by restoring intestinal mucosal barrier structure,reducing permeability,and inhibiting gut-derived inflammation mediated by the TLR4/NF-κB pathway.This mechanism of"gut-liver co-treatment"provides molecular biological evidence for the TCM theory of"fortifying the spleen to treat liver disease.".关键词
肝纤维化/黄连温胆汤/肠黏膜屏障/TLR4/NF-κB通路/肝病实脾Key words
hepatic fibrosis/Huanglian Wendan Decoction/intestinal mucosal barrier/TLR4/NF-κB pathway/fortifying the spleen to treat liver disease分类
医药卫生引用本文复制引用
唐博翔,陈美丽,廖小妹,王玺舜,余家乐,李涵宇,何文智..基于"肝病实脾"理论探讨黄连温胆汤通过修复肠屏障及抑制TLR4/NF-κB通路抗肝纤维化的作用机制[J].湖南中医药大学学报,2025,45(11):2063-2071,9.基金项目
湖南省自然科学基金项目(2025JJ90044) （2025JJ90044）
湖南省卫生健康委员会项目(D202308018795). （D202308018795）
