丹芪护肝方对肝纤维化模型大鼠TGF-β/Smad4信号通路的影响  

Effect of Danqi Hugan prescription on TGF-β/Smad4 signal pathway in liver fibrosis model rats

作　　者：彭馥芝 徐仪昕 蒋堃 陈思源[1] 余曦明[1] 张逢 余望贻[1] PENG Fuzhi;XU Yixin;JIANG Kun;CHEN Siyuan;YU Ximing;ZHANG Feng;YU Wangyi(Science and Technology Innovation Center,Hunan University of Chinese Medicine,Hunan,Changsha 410208,China)

机构地区：[1]湖南中医药大学科技创新中心,湖南长沙410208

出　　处：《中国医药科学》2023年第17期21-25,共5页China Medicine And Pharmacy

基　　金：湖南创新型省份建设专项(2020JJ4460);湖南省中医药科研计划项目(D2022098)

摘　　要：目的探讨丹芪护肝方通过转化生长因子-β(TGF-β)/信号通路通用调节因子4(Smad4)信号通路对大鼠肝纤维化的保护作用。方法取48只sqrague dawley(SD)大鼠,随机分成正常对照组、模型组、联苯双酯组和丹芪护肝方组,每组12只。腹腔注射40%四氯化碳大豆油溶液(1 ml/kg)建立大鼠肝纤维化模型。造模的同时,联苯双酯组(50 mg/kg)和丹芪护肝方组(9.14 g/kg)灌胃给药,正常对照组与模型组给予等体积生理盐水。8周后,全自动生化分析仪检测肝功能指标丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(T-BiL)、直接胆红素(D-BiL);逆转录-聚合酶链反应(RT-PCR)和蛋白免疫印迹(Western blot)测定平滑肌肌动蛋白(α-SMA)、转化生长因子β1(TGF-β1)、Smad4的信使核糖核酸(mRNA)及蛋白表达水平。结果与正常对照组比较,模型组大鼠血清中ALT、AST、T-BiL、D-BiL水平均升高,差异有显著统计学意义(P<0.01),肝组织内α-SMA、TGF-β1及Smad4 mRNA和蛋白表达均升高差异有显著统计学意义(P<0.01)。与模型组比较,丹芪护肝方干预后,大鼠血清中ALT、AST、T-BiL、D-BiL水平均降低,差异有统计学意义(P<0.05);肝脏组织中的α-SMA、TGF-β1和Smad4 mRNA和蛋白表达均降低,差异有显著统计学意义(P<0.01)。结论丹芪护肝方能抑制大鼠肝纤维化程度,其机制可能与TGF-β/Smad4信号通路有关。Objective To explore the protective effect of Danqi Hugan Prescription on liver fibrosis in rats through transforming growth factor-β(TGF-β)/signal pathway general regulator 4(Smad4).Methods A total of 48 sqrague dawley(SD)rats were randomly divided into the normal control group,model group,bifendate group and Danqi Hugan prescription group,with 12 rats in each group.The rat liver fibrosis model was established by intraperitoneal injection of 40%carbon tetrachloride soybean oil solution(1 ml/kg).At the same time,the bifendate group(50 mg/kg)and the Danqi Hugan Prescription group(9.14 g/kg)were given bifendate/Danqi Hugan Prescription by gavage,while the normal control group and the model group were given equal volume of normal saline.Eight weeks later,the liver function indexes such as alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(T-BiL)and direct bilirubin(D-BiL)were detected by automatic biochemical analyzer.The mRNA and protein expression levels of alpha-smooth muscle actin(α-SMA),transforming growth factorβ-1(TGF-β-1)and Smad4 were determined by reverse transcription-polymerase chain reaction(RT-PCR)and Western blot.Results Compared with the normal control group,the serum levels of ALT,AST,T-BiL and D-BiL in the model group all increased,with statistically significant differences(P<0.01),and the mRNA and protein expressions ofα-SMA,TGF-β1 and Smad4 mRNA the liver tissue were all increased,with statistically significant differences(P<0.01).Compared with the model group,the serum levels of ALT,AST,T-BiL,D-BiL in the Danqi Hugan Prescription group decreased significantly,with statistically significant differences(P<0.05),and the mRNA and protein expressions ofα-SMA,TGF-β1 and Smad4 in the liver tissue all decreased,with statistically significant differences(P<0.01).Conclusion Danqi Hugan Prescription can inhibit the degree of liver fibrosis in rats,and its mechanism may be related to TGF-β/Smad 4 signaling pathway.

关 键 词：丹芪护肝方 肝纤维化 转化生长因子Β1 信号通路通用调节因子4 

分 类 号：R285.5[医药卫生—中药学]