摘要
目的探讨大王马先蒿对肝纤维化的保护作用。方法将昆明小鼠随机分为正常对照组、模型对照组、秋水仙碱(0.1 mg·kg^(-1))组及大王马先蒿小(200 mg·kg^(-1))、中(400 mg·kg^(-1))、大(800 mg·kg^(-1))剂量组,每组10只;通过腹腔注射四氯化碳(CCl_(4),1 mL·kg^(-1))建立肝纤维化模型,并于第5周开始灌胃给药,每天1次,持续至第12周结束;末次给药后1 h,麻醉眼球取血检测血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原(PCⅢ)及IV型胶原(Ⅳ-C)水平,处死小鼠并取出脏器,计算小鼠脏器系数,Western blotting检测肝组织TGF-β_(1),Smad3,α-SMA及Collagen Ⅰ表达,苏木精-伊红(HE)和马松(Masson)染色观察小鼠肝组织病理形态。结果模型对照组小鼠皮毛竖立,活动减少,反应迟缓,大王马先蒿组小鼠一般状态好于模型对照组,反应较敏捷,皮色白有光泽。与模型对照组比较,大王马先蒿各剂量均能显著改善CCl_(4)所致小鼠肝组织的肝纤维化程度,显著降低血清ALT、AST、HA、LN、PCⅢ及Ⅳ-C水平(P<0.01),显著下调TGF-β_(1),Smad3,α-SMA及Collagen Ⅰ蛋白表达(P<0.01)。结论大王马先蒿对CCl_(4)诱导的肝纤维化小鼠具有较好的保护作用,该作用可能与抑制TGF-β_(1)/Smad信号通路及下调α-SMA和Collagen Ⅰ蛋白的表达有关。
Objective To evaluate the protective effect of Pedicularis rex(P.Rex)on liver fibrosis in mice.Methods Kunming mice were randomly divided into groups(n=10)of normal control group,model control group,colchicine(0.1 mg·kg^(-1))group,low(200 mg·kg^(-1)),medium(400 mg·kg^(-1))and high(800 mg·kg^(-1))doses of P.rex;The liver fibrosis model was established by intraperitoneal injection of CCl_(4)(1 mL·kg^(-1)).At the beginning of the 5th week,drugs were given intragastrically once a day for seven consecutive weeks.One hour after the last administration,all mice were anesthetized and the whole blood samples were collected for the determination of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),hyaluronic acid(HA),laminin(LN),procollagen typeⅢ(PCⅢ),and collagen typeⅣ(Ⅳ-C)levels;organs were then taken out and weighed for the calculation of mouse organ coefficients;liver tissues were tested by Western blotting for TGF-b1,Smad3,α-SMA,and Collagen Ⅰ proteins;HE and Masson staining were used for pathological morphology examination of mouse liver tissue.Results The fur of mice in the model control group was erected,and the mice have reduced activity and slow response.The general status of the mice in the P.rex groups was better than that in the model control group.Compared with those levels in the model group,the serum ALT,AST,HA,LN,PCⅢ,andⅣ-C levels of mice in all P.rex groups were decreased significantly(P<0.01).All doses of P.rex reduced the degree of liver fibrosis induced by CCl_(4) and significantly down-regulated the expressions of TGF-β_(1),Smad3,α-SMA,and collagen I proteins(P<0.01).Conclusion P.rex had a good protective effect on CCl_(4)-induced liver fibrosis in mice,and the effect might be related to its inhibition in TGF-β_(1)/Smad signaling pathway and down-regulation of theα-SMA and collagen I protein expression.
作者
张春雷
吴新玉
王栋
陆倩
董莉
张金娟
廖尚高
ZHANG Chunlei;WU Xinyu;WANG Dong;LU Qian;DONG Li;ZHANG Jinjuan;LIAO Shanggao(School of Pharmacy&State Key Laboratory of Functions and Applications of Medicinal Plants,Guizhou Medical University,Guian New Area 550025,China;Engineering Research Center for the Development and Application of Ethnic Medicine and TCM,Ministry of Education&Guizhou Provincial Key Laboratory of Pharmaceutics,Guizhou Medical University,Guiyang 550004,China;School of Basic Medical Sciences,Guizhou Medical University,Guian New Area 550025,China)
出处
《医药导报》
CAS
北大核心
2022年第4期423-429,共7页
Herald of Medicine
基金
贵州省高层次创新型人才百层次人才项目资助项目(20206011)
贵州省中药、民族药活性物质筛选新技术开发应用创新人才团队资助项目(20205006)
贵州省卫生健康委员会科学技术基金项目(gzwkj2021-452)。