现代中西医结合杂志2025，Vol.34Issue(19)：2635-2642,2648,9.DOI:10.3969/j.issn.1008-8849.2025.19.002
基于GARP/TGF-β1信号通路探讨鳖龙软肝汤对肝纤维化大鼠的影响
Bielong Ruangan decoction alleviates hepatic fibrosis and prevents hepatocellular carcinoma in rats via GARP/TGF-β1 signaling pathway
摘要
Abstract
Objective It is to explore the effect and mechanism of Bielong Ruangan decoction on rats with liver fibrosis based on glycoprotein A repetitions predominant(GARP)/transforming growth factor-β1(TGF-β1)signaling pathway.Methods Sixty SPF male SD rats were randomly divided into 4 groups:normal group,model group,low dose Bielong Ruan-gan decoction group and high dose Bielong Ruangan decoction group,with 15 rats in each group.The rats of all groups except for the normal group were intraperitoneally injected with DEN 50mg/kg to establish precancerous lesion models of hepatic fi-brosis/cirrhosis-hepatocellular carcinoma,continuously treated for 16 weeks.Starting from the 8th week of experiment,the low and high dose groups of Bielong Ruangan decoction were respectively given Bielong Ruangan decoction6.84 g/(kg·d),27.36 g/(kg·d)by gavage,all twice daily,continuously gavaged for 8 weeks.During the experiment,the general condi-tions of rats in each group were monitored,including growth and development,mental status,and dietary intake.7 rats from each group were randomly sacrificed at the end of the 12th week of experiment,the remaining 8 rats in each group were sacrificed at the end of the 16th week to observe their liver general condition with naked eyes,and the liver-body weight ratio was calculated at the end of the 16th week,hepatic histopathology was observed by HE staining,and liver fi-brosis was graded,the expression of proliferating cell nuclear antigen(PCNA)in liver tissue was detected by immunohisto-chemical staining,the protein expressions of GARP and TGF-β1 in liver tissue were detected by Western blot and immuno-fluorescence assays.Results Compared with the normal group,the general condition of rats in the model group was poor,and nodules were visible on the surface of most livers;the liver weight ratio was significantly increased at the end of the 16 th week of experiment(P<0.05);obvious fibrous septum and connective tissue hyperplasia were observed in the liver tis-sue,and the liver fibrosis score was significantly increased at the end of the 16 th week(P<0.05);at the end of the 12 th and 16 th week of experiment,the positive staining area of PCNA,the relative protein expressions of GARP and TGF-β1,and the fluorescence intensities of GARP and TGF-β1 protein expressions in liver tissue were significantly increased(all P<0.05).Compared with the model group,the general condition of rats in the high dose Bielong Ruangan decoction group was improved,the number of nodules on the liver surface was reduced,and the liver weight ratio was significantly re-duced at the end of the 16 th week(P<0.05);the fibrous septum of liver tissue was less,and the proliferation of connec-tive tissue was not obvious,the liver fibrosis score was significantly decreased at the end of the 16 th week(P<0.05);the positive staining area of PCNA,the relative protein expressions of GARP and TGF-β1,and the fluorescence intensities of GARP and TGF-β1 protein expression in liver tissue were significantly decreased at the 12 th and 16 th weeks of experiment(all P<0.05).Only the positive staining area of PCNA in liver tissue at the end of the 12 th week,the relative protein ex-pressions of GARP and TGF-β1 in liver tissue at the end of the 16 th week,the fluorescence intensity of GARP protein ex-pression in liver tissue at the end of the 12 th week and the fluorescence intensity of TGF-β1 protein expression in liver tis-sue at the end of the 16 th week were significantly lower in the low dose Bielong Ruangan decoction group than those in the model group(all P<0.05).Conclusion Bielong Ruangan decoction can improve hepatic fibrosis and prevent the occur-rence and progression of liver cancer in rats with hepatic fibrosis,the therapeutic mechanism may be related to the regula-tion of GARP/TGF-β1 signaling pathway.关键词
肝细胞癌/肝纤维化/癌前病变/鳖龙软肝汤/糖蛋白A为主的重复序列/转化生长因子-β1Key words
hepatocellular carcinoma/hepatic fibrosis/precancerous lesion/Bielong Ruangan decoction/glycoprotein A repetitions predominant/transforming growth factor-β1分类
医药卫生引用本文复制引用
李倩,银思涵,彭憬,周意..基于GARP/TGF-β1信号通路探讨鳖龙软肝汤对肝纤维化大鼠的影响[J].现代中西医结合杂志,2025,34(19):2635-2642,2648,9.基金项目
湖南省中医药管理局科研计划项目(D2022059) （D2022059）
湖南省自然科学基金项目(2024JJ9442) （2024JJ9442）
国家中医药管理局高水平中医药重点学科建设项目(zyyzdxk-2023146) （zyyzdxk-2023146）
湖南中医药大学双一流学科建设项目(2018[03]) （2018[03]）
