中国中医药信息杂志2024，Vol.31Issue(5)：61-67,7.DOI:10.19879/j.cnki.1005-5304.202310283
肝豆汤Ⅱ号调控TGF-β1/Smad通路抑制肝豆状核变性小鼠肝纤维化的机制研究
Study on the Mechanism of Gandou Decoction Ⅱ in Regulating TGF-β1/Smad Pathway to Inhibit Hepatic Fibrosis in Wilson Disease Mice
摘要
Abstract
Objective To study the effects and mechanism of Gandou Decoction Ⅱ in regulating TGF-β1/Smad pathway for hepatic fibrosis in Wilson disease mice.Methods DL mice were set as the control group,while TX mice were randomly divided into the model group,TCM low-and high-dosage groups.TCM groups were given routine dosage and high-dosage Gandou Decoction Ⅱ by gavage respectively,while the control group and model group were administered distilled water by gavage for 30 consecutive days.ELISA was used to detect the contents of alanine aminotransferase(ALT),aspartate aminotransferase(AST),collagen type Ⅳ(ColⅣ),hyaluronic acid(HA),procollagen type Ⅲ(HPCⅢ),and laminin(LN)in serum,Masson staining was used to observe the degree of liver tissue fibrosis,while immunofluorescence staining was used to detect α-SMA expression in liver tissue,inductively coupled plasma mass spectrometry was used to detect copper and iron ion content in liver tissue,and RT-qPCR was used to detect the expressions of α-SMA,collagen type Ⅰ(ColⅠ),transforming growth factor-β1(TGF-β1),and Smad2/3 mRNA in liver tissue,Western blot was used to detect of protein expressions of α-SMA,ColⅠ,TGF-β1,p-Smad2/3 and Smad2/3 in liver tissue.Results Compared with the control group,the contents of serum ALT,AST,ColⅣ,HA,HPCⅢ and LN significantly increased in the model group(P<0.05,P<0.01),the collagen volume fraction of liver tissue significantly increased,the expression of α-SMA significantly increased(P<0.01),the iron ion content in liver tissue significantly increased(P<0.01),α-SMA,ColⅠ,TGF-β1,Smad2/3 mRNA and protein expressions significantly increased,and the expression of p-Smad2/3 protein significantly increased(P<0.05,P<0.01).Compared with the model group,the contents of serum ALT,AST,ColⅣ,HA,HPCⅢ and LN significantly decreased in TCM low-and high-dosage groups(P<0.05,P<0.01),the collagen volume fraction of liver tissue significantly decreased,the expression of α-SMA significantly decreased(P<0.01),and the copper and iron ion content in liver tissue significantly increased(P<0.01),α-SMA,ColⅠ,TGF-β1,Smad2/3 mRNA and protein expressions were significantly decreased,and p-Smad2/3 protein expression significantly decreased(P<0.05,P<0.01).Conclusion Gandou Decoction Ⅱ can regulate TGF-β1/Smad pathway to down-regulate the expressions of ColⅠ,α-SMA,and TGF-β1,inhibit hepatic fibrosis in Wilson disease mice and alleviate copper accumulation induced liver pathological damage.关键词
肝豆状核变性/肝豆汤Ⅱ号/肝纤维化/TGF-β1/Smad通路/小鼠Key words
Wilson disease/Gandou Decoction Ⅱ/liver fibrosis/TGF-β1/Smad pathway/mice分类
医药卫生引用本文复制引用
周丹,董健健,程楠,韩咏竹..肝豆汤Ⅱ号调控TGF-β1/Smad通路抑制肝豆状核变性小鼠肝纤维化的机制研究[J].中国中医药信息杂志,2024,31(5):61-67,7.基金项目
安徽省自然科学基金(2208085MH226) （2208085MH226）
安徽省高等学校科学研究项目(2023AH050778) （2023AH050778）
合肥综合性国家科学中心大健康研究院新安医学与中医药现代化研究所"揭榜挂帅"项目(2023CXMMTCM002) （2023CXMMTCM002）
