摘要
目的探讨Beta-谷甾醇对四氯化碳(carbon tetrachloride,CCL 4)诱导的小鼠肝纤维的作用与机制。方法50只C57BL/6♂小鼠随机分成5组:正常组、CCL 4组、Beta-谷甾醇低中高剂量组(BS-L/M/H),每组10只。腹腔注射CCL 4制肝纤维化模型,共30 d,于前15 d灌胃不同剂量Beta-谷甾醇。处死后,观察大体形态,测量肝指数,HE和Masson染色观察肝组织和胶原纤维,Elisa测血清(ALT)、(AST)变化,免疫组化和Western blot检测α-SMA、CollagenⅠ的表达,Elisa和Western blot检测信号通路TNF-α-NF-κB和TβR1-Smad2/3的变化。结果与正常组比,BS各组显著性地抑制了CCL 4引起的肝指数、ALT、AST、α-SMA、collagenⅠ的增高,该作用呈量效依赖性(P<0.05或P<0.01),BS各组肝形态、炎症细胞浸润与胶原纤维变化也呈剂量依赖性优于模型组,同时,BS-M降低了信号通路中TβR1、Smad2/3、TNF-α和p-NF-κB因子的表达(P<0.05)。结论Beta-谷甾醇呈剂量依赖抑制CCL 4诱导的小鼠肝纤维化,且其作用机制与抑制TNF-α-NF-κB和TβR1-Smad2/3信号通路相关。
Aim To explore the effect of beta-sitosterol(BS)on liver fibrosis induced by CCL 4 in mice and the mechanisms.Methods Fifty C57BL/6 male mice were randomly divided into five groups:control group(CG),carbon tetrachloride group(CTG),low/medium/high dose of BS group(BS-L/M/H),with 10 mice in each group.The model of hepatic fibrosis was established by injecting CCL 4 in peritoneal cavity,the study lasted 30 days,and different doses of BS were given from 1st day to 15th day.All mice were sacrificed for the observation of morphological changes and the measurement of liver index.Liver collagenous fibers were observed by HE and Masson staining,the changes of serum(ALT and AST)were assessed by Elisa,the expressions ofα-SMA and Collagen I were detected by Western blot and immunohistochemistry,and the changes of TβR1-Smad2/3 and TNF-α-NF-κB were detected by Elisa and Western blot.Results Compared to control group,different doses of BS markedly inhibited the increase of liver index,ALT,AST,α-SMA and Collagen I in a dose-dependent manner(P<0.05 or P<0.01).Liver morphology,inflammatory cell infiltration and collagenous fiber in BS groups were better than those in CCL 4 group,meanwhile BS-M decreased the expression of TβR1,Smad2/3,TNF-αand p-NF-κB(P<0.01).Conclusions BS dose-dependently inhibits mouse liver fibrosis induced by CCL 4,and its mechanism may be related to inhibiting TβR1-Smad2/3 and TNF-α-NF-κB signaling pathways.
作者
万星
李相国
李修贤
吕慧芬
黄德斌
胡泽华
WAN Xing;LI Xiang-guo;LI Xiu-xian;LYU Hui-fen;HUANG De-bin;HU Ze-hua(Dept of Functional Sciences,Medical College,Hubei Minzu University,Enshi Hubei 445000,China;Medical College,Science and Technology College,Hubei Minzu University,Enshi Hubei 445000,China;Dept of Traditional Chinese Medicine,Medical College,Hubei Minzu University,Enshi Hubei 445000,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2020年第1期75-80,共6页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 81560675)
