人参皂苷Rh1抗肝纤维化的作用机制研究  

Mechanisms of the Anti-Fibrotic Effect of Ginsenoside Rh1 on Hepatic Fibrosis

作　　者：陈煊 杨赛 南博[3] 马吉胜 王艳芳[1,4] CHEN Xuan;YANG Sai;NAN Bo;MA Jisheng;WANG Yanfang(College of Chinese Medicinal Materials,Jilin Agricultural University,Changchun 130118,China;School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou 325035,China;College of Food Science and Engineering,Jilin Agricultural University,Changchun 130118,China;Laboratory for Cultivation and Breeding of Medicinal Plants,National Administration of Traditional Chinese Medicine,Changchun 130118,China)

机构地区：[1]吉林农业大学中药材学院,长春130118 [2]温州医科大学药学院,温州325035 [3]吉林农业大学食品科学与工程学院,长春130118 [4]国家中医药管理局药用植物栽培育种实验室,长春130118

出　　处：《四川大学学报(医学版)》2025年第1期120-128,共9页Journal of Sichuan University(Medical Sciences)

基　　金：吉林省科技发展计划项目(No.20210204040YY)资助。

摘　　要：目的研究稀有人参皂苷Rh_(1)(ginsenoside Rh_(1),G-Rh_(1))是否可以降低由胆碱缺乏,L-氨基酸缺乏的高脂饮食(choline-deficient,L-amino acid-defined,high-fat diet,CDAHFD)诱导的肝纤维化,并探讨其可能存在机制。方法将雄性C57BL/6J小鼠随机分为标准饲料组(Control组)、高脂饲料组(CDAHFD组)、水飞蓟素组(Silymarin,5 mg/kg)、G-Rh_(1)低剂量组(5 mg/kg)、G-Rh_(1)中剂量组(10 mg/kg)、G-Rh_(1)高剂量组(20 mg/kg),每组8只。Control组正常喂养,其余小组均以CDAHFD连续喂养7周建立小鼠肝纤维化模型;于第一周起,各给药组小鼠分别灌胃相应药液,每天1次,连续7周。末次给药后,称定各组小鼠体质量、脏器质量并得出脏器指数;HE染色、天狼星红染色和免疫组织化学染色(IHC)观察肝脏组织;Western blot检测肝纤维化相关蛋白α-平滑肌肌动蛋白(α-SMA)、转化生长因子-β1(TGF-β1)1,通路相关蛋白成纤维细胞生长因子12(FGF-12);检测血清生化指标天冬氨酸转移酶(AST)、丙氨酸转氨酶(ALT)、总胆红素(TBIL)和直接胆红素(DBIL)。将小鼠巨噬细胞(RAW246.7)随机分为5组〔对照组、脂多糖(LPS)组、3个给药组〕。除对照组RAW246.7细胞只含有RAW246.7细胞和培养基外,其余组RAW246.7细胞均加入培养基、RAW246.7细胞和LPS(终浓度500 ng/mL),3个给药组在此基础上分别加入10μmol/L、20μmol/L、40μmol/L G-Rh_(1)。取5组RAW264.7细胞的上清液与大鼠肝星状细胞(HSC-T6)共培养24 h,观察比较G-Rh_(1)或LPS对HSC-T6中α-SMA、Ⅰ-a1型胶原蛋白(Col1a1)等纤维化相关蛋白,及对RAW264.7中FGF-12和p-STAT3/STAT3纤维化信号通路相关蛋白表达的影响;流式分析检测RAW264.7表型;ELISA检测促纤维化因子单核细胞趋化蛋白1(MCP-1)和TGF-β。结果与正常Control组比较,CDAHFD组小鼠明显出现肝纤维化。与CDAHFD小鼠比较,G-Rh_(1)给药组小鼠肝纤维化均有一定缓解,存在剂量依赖相关性,且缓解效果优于对照药物水飞�Objective To investigate whether ginsenoside Rh_(1)(G-Rh_(1))can alleviate liver fibrosis induced by a choline-deficient,L-amino acid-defined,high-fat diet(CDAHFD)and to explore its underlying mechanisms.Methods Male C57BL/6J mice were randomly divided into 6 groups(n=8 in each group),including a standard diet group(or the control group),a high-fat diet group(or the CDAHFD group),a silymarin group(given silymarin at 5 mg/kg),a low-dose G-Rh_(1) group(given G-Rh_(1) at 5 mg/kg),a medium-dose G-Rh_(1) group(given G-Rh_(1) at 10 mg/kg),and a high-dose G-Rh_(1) group(given G-Rh_(1) at 20 mg/kg).The control group was given a standard feed,while the other groups were fed CDAHFD for 7 weeks to establish the mouse model of liver fibrosis.Starting from the first week,the mice in the treatment groups were administered the corresponding drugs by intragastric gavage once daily for 7 weeks in succession.After the administration of the final drug treatment,the body mass and organ mass of the mice in different groups were measured,and the organ index was obtained according.Liver tissues were examined using HE staining,Sirius red staining,and immunohistochemistry(IHC)staining.Western blot was performed to measureα-smooth muscle actin(α-SMA)and transforming growth factor-β1(TGF-β1),two liver fibrosis-related proteins,and fibroblast growth factor 12(FGF-12),a pathway-related protein.The serum biochemical indicators,including aspartate transferase(AST),alanine aminotransferase(ALT),total bilirubin(TBIL),and direct bilirubin(DBIL),were measured.Additionally,RAW246.7 cells were randomly divided into 5 groups,including a control group,a lipopolysaccharide(LPS)group,and 3 G-Rh_(1) treatment groups.The control group had only RAW246.7 cells in the culture medium.The other groups were given LPS(500 ng/mL),and the 3 treatment groups received G-Rh_(1) at 10,20,and 40μmol/L in addition.The supernatants from the 5 groups of RAW246.7 cells were collected and cocultured with HSC-T6 cells for 24 hours to observe and compare the effects of G

关 键 词：人参皂苷RH1 肝纤维化 巨噬细胞 肝星状细胞 FGF-12 

分 类 号：R285.5[医药卫生—中药学]