西安交通大学学报（医学版）2025，Vol.46Issue(4)：616-621,6.DOI:10.7652/jdyxb202504010
没药甾酮抑制二乙基亚硝胺诱导的大鼠肝纤维化及机制
Inhibitory effect of guggulsterone on diethylnitrosamine-induced liver fibrosis in rats and its mechanism
摘要
Abstract
Objective To explore the inhibitory effect of guggulsterone(GS)on diethylnitrosamine(DEN)-induced liver fibrosis in rats and its mechanism.Methods DEN-induced liver fibrosis model was established in SD rats.The successful model rats were randomly divided into model group(n=6),GS group(n=6,50 mg/kg,intraperitoneal injection for 4 weeks),GS+SRI group(n=6,50 mg/kg+30 mg/kg,intraperitoneal injection for 4 weeks),and control group(n=6,without DEN-induced).Rats in the control group and the model group were injected with the same amount of normal saline.The pathological changes of the liver were detected by HE staining.Serum liver function indexes including alanine aminotransferase(ALT),aspartate aminotransferase(AST),albumin(ALB)and alkaline phosphatase(ALP)were detected by automatic biochemical analyzer.The serum levels of pro-collagen Ⅲ(PC-Ⅲ),collagen Ⅳ(Ⅳ-C),hyaluronidase(HA),laminin(LN),malondialdehyde(MDA),reduced glutathione(GSH),superoxide dismutase(SOD),and catalase(CAT)were detected by ELISA assay.The mRNA and protein expression of TGF-β1,Smad2,and p-Smad3/Smad3 were detected by Real-time PCR and Western blotting.Results Compared with the control group,the model group showed typical pathological changes of liver fibrosis;the serum ALB,GSH,SOD and CAT levels were significantly decreased(P＜0.05);the serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA,LN and the mRNA expression of TGF-β1,Smad3 and protein expression of TGF-β1,p-Smad3 in liver tissues were significantly increased(P＜0.05).Compared with the model group,the pathological changes of liver fibrosis in the GS group were alleviated,and the serum levels of ALB,GSH,SOD and CAT were significantly increased(P＜0.05),the serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA and LN,the mRNA expression of TGF-β1 and Smad3,and protein expression of TGF-β1 and p-Smad3 in liver tissues were significantly decreased(P＜0.05).In addition,after the administration of SRI,TGF-β1 signaling pathway activator,compared with the GS group,the GS+SRI group showed significantly decreased serum ALB,GSH,SOD and CAT levels(P＜0.05),but significantly increased serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA and LN as well as the mRNA expression of TGF-β1 and Smad3 and protein expression of TGF-β1 and p-Smad3 in liver tissues(P＜0.05).Therefore,SRI attenuated the anti-fibrotic effect of GS on rats with liver fibrosis.Conclusion GS has certain inhibitory effect on DEN-induced liver fibrosis in rats,and its mechanism may be related to the reduction of oxidative stress level and the inhibition of the activation of TGF-β1/Smad3 signaling pathway.关键词
没药甾酮/肝纤维化/氧化应激/TGF-β/Smad信号通路Key words
guggulsterone/liver fibrosis/oxidative stress/TGF-β/Smad signaling pathway分类
医药卫生引用本文复制引用
刘雄涛,秦变妮,李波,薛鹏军,席红娜,李静,郭军,石娟娟..没药甾酮抑制二乙基亚硝胺诱导的大鼠肝纤维化及机制[J].西安交通大学学报（医学版）,2025,46(4):616-621,6.基金项目
陕西省自然科学基础研究计划项目(No.2023-JC-YB-770)Supported by the Natural Science Basic Research Program of Shaanxi Province(No.2023-JC-YB-770) （No.2023-JC-YB-770）
