Exploration on the Mechanism of Xiaomudan Granules in the Treatment of Non-alcoholic Fatty Liver Disease Based on mTORC1/USP20/HMGCR Pathway
10.19879/j.cnki.1005-5304.202401324
- VernacularTitle: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
- Author:
Yu HUANG
1
;
Ruijuan YAN
;
Junzhe JIAO
;
Shuguang YAN
;
Hailiang WEI
;
Zhanjie CHANG
;
Jingtao LI
;
Qian BIAN
Author Information
1. 陕西中医药大学第一临床医学院,陕西 咸阳 712000
- Keywords:
non-alcoholic fatty liver disease;
Xiaomudan Granules;
mTORC1/USP20/HMGCR pathway;
cholesterol synthesis;
rats
- From:
Chinese Journal of Information on Traditional Chinese Medicine
2024;31(8):110-116
- CountryChina
- Language:Chinese
-
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.
