湖南中医药大学学报2025，Vol.45Issue(1)：15-22,8.DOI:10.3969/j.issn.1674-070X.2025.01.003
壮药牛大力醇提物对四氯化碳诱导肝纤维化大鼠的改善作用研究
Improvement effects of ethanol extract from Zhuang medicine Millettia speciosa Champ.on carbon tetrachloride-induced hepatic fibrosis in rats
摘要
Abstract
Objective To investigate the therapeutic effects and mechanism of Millettia speciosa Champ.ethanol extract(MCEE)on carbon tetrachloride(CCl4)-induced hepatic fibrosis(HF)in rats.Methods An SD rat model with HF was established by intraperitoneal injection of 40％CCl4 olive oil solution(0.1 mL/100 g)twice a week for 12 consecutive weeks.HF rats were randomly divided into model group,low-,medium-,and high-dose MCEE(3.5,7,14 g/kg)groups,positive control colchicine(0.12 mg/kg)group,and normal group,with eight rats in each group.Each medication group was given the corresponding drug intervention by gavage at the set dose since the 9th week of modeling,once a day for four consecutive weeks.The normal group and model group were given an equal volume of normal saline by gavage every day.The liver and spleen indexes of rats were measured 24 hours after the last administration;serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),malondialdehyde(MDA),superoxide dismutase(SOD),hyaluronic acid(HA),laminin(LN),type Ⅲ procollagen(PC Ⅲ),collagen Ⅳ(Ⅳ-C),transforming growth factor-β1(TGF-β1),interleukin-1β(IL-1β),interleukin-8(IL-8),and interleukin-6(IL-6)were determined;HE staining and Masson staining were used to observe the pathological changes in liver tissue;Western blot was used to measure the protein levels of Kelch-like ECH-associated protein-1(Keap1),nuclear factor-erythroid 2-related factor 2(Nrf2),heme oxygenase-1(HO-1),and quinone oxidoreductase 1(NQO1)in rat liver.Results Compared with the normal group,rats in the model group showed delayed response,significantly increased liver and spleen indexes,and serum levels of ALT,AST,MDA,LN,HA,PC Ⅲ,Ⅳ-C,TGF-β1,IL-1β,IL-8,and IL-6(P<0.01),as well as significantly decreased SOD levels(P<0.01);they also exhibited obvious fibrosis in liver tissue,significantly increased Keap1 protein content in liver tissue(P<0.01),and significantly decreased protein levels of Nrf2,HO-1,and NQO1(P<0.01).Compared with the model group,the condition of rats in MCEE groups with all doses was significantly improved,with significant reductions in the liver and spleen indexes and serum levels of ALT,AST,MDA,LN,HA,PCⅢ,Ⅳ-C,TGF-β1,IL-1β,IL-8,and IL-6(P<0.05,P<0.01),and a significant increase in SOD expression(P<0.01);the pathological damage and fibrosis in rat liver tissue were effectively alleviated;the expression of Keap1 in liver tissue was significantly inhibited(P<0.01),while the protein content of Nrf2,HO-1,and NQO1 significantly increased(P<0.05,P<0.01).Compared with the colchicine group,the high-dose MCEE group had a stronger regulatory effect on the above indicators,and the improvement effects were enhanced with increasing MCEE dosage.Conclusion MCEE has a significant anti-HF effect,and its mechanism of action may be related to antioxidant activity,inhibition of inflammatory cytokine expression,and regulation of the Keap1/Nrf2 signaling pathway.关键词
牛大力/醇提物/肝纤维化/抗氧化/炎症因子/Keap1/Nrf2信号通路Key words
Millettia speciosa Champ./ethanol extract/hepatic fibrosis/antioxidation/inflammatory factors/Keap1/Nrf2 signaling pathway分类
医药卫生引用本文复制引用
侯玲,覃妮,陆世银,陈秋贵,磨奕玲,徐敏丽,卢鲜云,何烨,张洪平..壮药牛大力醇提物对四氯化碳诱导肝纤维化大鼠的改善作用研究[J].湖南中医药大学学报,2025,45(1):15-22,8.基金项目
广西中医药大学自然科学基金面上项目(2020MS055) （2020MS055）
柳州市科技攻关与新产品试制(2020NBAA0802). （2020NBAA0802）
