中国中医药信息杂志2024，Vol.31Issue(8)：110-116,7.DOI:10.19879/j.cnki.1005-5304.202401324
基于mTORC1/USP20/HMGCR通路探讨消木丹颗粒治疗非酒精性脂肪性肝病作用机制
Exploration on the Mechanism of Xiaomudan Granules in the Treatment of Non-alcoholic Fatty Liver Disease Based on mTORC1/USP20/HMGCR Pathway
摘要
Abstract
Objective To observe the effects of Xiaomudan Granules on cholesterol synthesis in rats with non-alcoholic fatty liver disease(NAFLD);To explore its mechanism on the treatment of NAFLD based on mTORC1/USP20/HMGCR pathway.Methods Totally 60 SD rats were randomly divided into blank group,model group,Western medicine group(polyene phosphatidylcholine)and TCM low-,medium-and high-dosage groups(Xiaomudan Granules).The blank group was fed with ordinary diet,and the other groups were fed with high-fat diet for 12 weeks to establish NAFLD rat model.After successful modeling,each administration group was given the corresponding drug intragastric administration,and the blank group and model group were given aseptic distilled water intragastric administration for 4 weeks.Body mass and liver mass of rats were recorded,liver index was calculated,and serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)contents were detected by automatic biochemical analyzer,the morphological changes of liver tissue were observed by HE staining and oil red O staining,real-time fluorescence quantitative PCR and Western blot were used to detect ribosome S6 kinase(S6K),ubiquitin specific protease 20(USP20),3-hydroxy-3-methylglutaryl CoA reduction enzyme(HMGCR)mRNA and p-S6K,S6K,USP20,HMGCR protein expression in liver tissue.Results Compared with the blank group,the body mass,liver mass and liver index of rats in model group significantly increased(P<0.01,P<0.05),the volume of liver lobe increased,the edge was blunted;the contents of serum ALT,AST,TC,TG and LDL-C significantly increased,while HDL-C content significantly decreased(P<0.01);most hepatocytes showed steatosis,significant vacuole and inflammatory infiltration,increased lipid droplets,and significantly increased mRNA expression of USP20 and HMGCR in liver tissue(P<0.01)and protein expressions of p-S6K,USP20 and HMGCR(P<0.01).Compared with the model group,TCM high-dosage group and Western medicine group could significantly decrease body mass,liver mass and liver index of rats(P<0.01,P<0.05),and improve the appearance of liver;decrease the contents of ALT,AST,TC and LDL-C in serum,and increase the content of HDL-C(P<0.01,P<0.05);alleviate hepatocyte steatosis and balloon-like degeneration,reduce lipid droplet deposition,and decrease USP20,HMGCR mRNA and p-S6K,USP20,HMGCR protein expression in liver tissue(P<0.01,P<0.05).Conclusion Xiaomudan Granules may regulate cholesterol synthesis through mTORC1/USP20/HMGCR pathway,and thus play a role in the treatment of NAFLD in rats.关键词
非酒精性脂肪性肝病/消木丹颗粒/mTORC1/USP20/HMGCR通路/胆固醇合成/大鼠Key words
non-alcoholic fatty liver disease/Xiaomudan Granules/mTORC1/USP20/HMGCR pathway/cholesterol synthesis/rats分类
医药卫生引用本文复制引用
黄玉,闫瑞娟,焦俊喆,闫曙光,魏海梁,常占杰,李京涛,边倩..基于mTORC1/USP20/HMGCR通路探讨消木丹颗粒治疗非酒精性脂肪性肝病作用机制[J].中国中医药信息杂志,2024,31(8):110-116,7.基金项目
陕西省教育厅青年创新团队建设科研计划(21JP032) （21JP032）
陕西省重点研发计划(2020ZDLSF05-15) （2020ZDLSF05-15）
陕西省自然科学基础研究计划(2022JQ-965) （2022JQ-965）
陕西省创新能力支撑计划(2022TD-55) （2022TD-55）
陕西省中医药管理局委托项目(SZY-KJCYC-2023-049、SZY-KJCYC-2023-087) （SZY-KJCYC-2023-049、SZY-KJCYC-2023-087）
陕西省中医药管理局"双链融合"中青年科研创新团队(2022-SLRH-LJ-002) （2022-SLRH-LJ-002）
咸阳市重点研发计划(L2022ZDYFSF007) （L2022ZDYFSF007）
