人参皂苷Rg_(1)对非酒精性脂肪性肝病小鼠肝纤维化的作用

Effect of Ginsenoside Rg_(1)on Liver Fibrosis in Mice with Non-alcoholic Fatty Liver Disease

目的:研究人参皂苷Rg_(1)对高脂饮食喂养诱导的非酒精性脂肪性肝病(NAFLD)小鼠肝纤维化的作用及机制。方法:50只雄性C57BL/6J小鼠分为正常对照组、模型组、二甲双胍(150 mg/kg)阳性对照组及人参皂苷Rg_(1)低(20 mg/kg)、高(40 mg/kg)剂量组,每组10只。除正常对照组外各组小鼠高脂饮食喂养24 w。造模开始12 w后,各给药组每天灌胃给予相应药物1次,连续12 w。药物处理至第12周时进行葡萄糖耐量实验和胰岛素耐量实验;检测体质量及血糖、胰岛素、瘦素、丙氨酸氨基转移酶、门冬酸氨基转移酶水平;取肝脏组织,HE染色观察肝脏组织病理学改变,天狼星红染色检测肝脏纤维化情况;相应试剂盒检测肝脏组织三酰甘油、总胆固醇含量,Western blot检测肝组织α-平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原蛋白(Collagen Ⅰ)、Ⅲ型胶原蛋白(Collagen Ⅲ)、转化生长因子-β_(1)(TGF-β_(1))、磷酸化Smad3(p-Smad3)、Wnt3a、β-连环蛋白(β-catenin)表达。结果:与模型组比较,人参皂苷Rg_(1)高剂量组大鼠体质量、胰岛素抵抗及血清葡萄糖、胰岛素、瘦素水平显著降低(P<0.05)。人参皂苷Rg_(1)低、高剂量组大鼠肝功能损伤、肝脂肪病变和肝纤维化明显改善,肝组织α-SMA、Collagen Ⅰ、Collagen Ⅲ、TGF-β_(1)、p-Smad3、Wnt3a、β-catenin蛋白表达显著降低(P<0.05)。结论:人参皂苷Rg_(1)能有效改善高脂饮食诱导的NAFLD肝纤维化,其机制可能与抑制TGF-β_(1)/Smad通路和Wnt/β-catenin通路有关。

Objective:To study the effect and mechanism of ginsenoside Rg_(1)on liver fibrosis in mice with non-alcoholic fatty liver disease(NAFLD)induced by high fat diet.Methods:Fifty male C57 BL/6 J mice were divided into normal control group,model group,positive control group with metformin(150 mg/kg)and ginsenoside Rg_(1)low-dose(20 mg/kg)and high-dose(40 mg/kg)groups,with 10 mice in each group.Except normal control group,mice in each group were fed high-fat diet for 24 weeks.Twelve weeks after the star of modeling,the mice in each drug treatment group were given correspoding drugs by gavage once a day for 12 weeks.Glucose tolerance test and insulin tolerance test were performed at the 12 th week of drug treatment.Body weight and the levels of blood glucose,insulin,leptin,alanine aminotransferase and aspartic acid aminotransferase were detected.Liver tissues were collected and the histopathdogical changes of liver were observed by HE staining.Liver fibrosis was detected by Sirius red staining.The contents of triacylglycerol,total cholesterol in liver tissue were detected by corresponding kit,the expressions of alpha smooth muscle actin(α-SMA),typeⅠCollagen(Collagen Ⅰ),type Ⅲ Collagen(Collagen Ⅲ),transforming growth factor beta 1(TGF-β_(1)),phosphorylation Smad3(p-Smad3),Wnt3 a,beta serial protein(β-catenin)in hepatic tissue were detected by Western blot.Results:Compared with the model group,the body weight,insulin resistance and blood glucose,insulin,leptin levels of mice in ginsenoside Rg_(1)high-dose group were significantly decreased(P<0.05).The rat liver damage,liver fat lesions and liver fibrosis significantly improve andα-SMA,Collagen Ⅰ,Collagen Ⅲ,TGF-β_(1),p-Smad3,Wnt3 a andβ-catenin protein expressions in liver tissues of mice in ginsenoside Rg_(1)low-dose and high-dose group decreased significantly(P<0.05).Conclusion:Ginsenoside Rg_(1)can effectively improve NAFLD liver fibrosis induced by high fat diet,and the mechanism may be related to the inhibition of TGF-β_(1)/Smad pathway and Wnt/β-catenin pathway.