Improvement effect of metformin on liver injury in non-alcoholic steatohepatitis rats
- VernacularTitle:二甲双胍对非酒精性脂肪性肝炎大鼠肝损伤的改善作用
- Author:
Shuang WU
1
;
Hailin CHENG
1
;
Dan LIU
1
;
Ting XIAO
1
;
Xingbang WU
1
;
Huadong LI
2
;
Xudong HU
1
Author Information
1. Dept. of Gastroenterology，Wuhan Jinyintan Hospital，Tongji Medical College of Huazhong University of Science and Technology （Hubei Clinical Research Center for Infectious Disease），Wuhan 430023，China
2. Dept. of Infection，Wuhan Jinyintan Hospital，Tongji Medical College of Huazhong University of Science and Technology （Hubei Clinical Research Center for Infectious Disease），Wuhan 430023，China
- Publication Type:Journal Article
- Keywords:
metformin;
non-alcoholic steatohepatitis;
liver damage;
lipid metabolism;
liver fibrosis;
PI3K/AKT/PDGF
- From:
China Pharmacy
2025;36(7):837-842
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the effects of metformin （Met） on liver injury in non-alcoholic steatohepatitis （NASH） rats by regulating the PI3K/AKT/PDGF signaling pathway. METHODS NASH model was constructed by feeding rats with a high- glucose and high-fat diet， and assigned into Model group， Met low-dose group （Met-L group， 100 mg/kg）， Met medium-dose group （Met-M group， 200 mg/kg）， Met high-dose group （Met-H group， 400 mg/kg）， and high dose of Met+PI3K activator group （Met-H+740 Y-P group， 400 mg/kg Met+50 mg/kg 740 Y-P）， with 12 rats in each group. Another 12 rats were regarded as the Control group. Each group of rats was orally administered/injected with the corresponding medication once a day for 6 consecutive weeks. The changes in body weight and liver index of rats were recorded and analyzed. The pathological damage [evaluation of non-alcoholic fatty liver disease activity score （NAS）]， lipid deposition （calculation of the proportion of oil red O-positive staining area）， and fibrosis （calculation of collagen deposition score） were observed in liver tissue of rats. The levels of inflammatory factors [interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）] in serum and liver tissue， the levels of serum lipid metabolism indicators [total cholesterol （TC）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）] and liver function indicators [aspartate aminotransferase （AST） and alanine Δ 基金项目 武汉市知识创新专项项目（No.2022020801010588）； aminotransferase （ALT）] were measured. The expression levels of PI3K/AKT/PDGF signaling pathway-related proteins and Caspase-3 in liver tissue of rats were determined. RESULTS Compared with the Control group， body weight， liver index， the levels of serum lipid metabolism indicators and liver function indicators， the levels of IL-6 and TNF-α in serum and liver tissue， the NAS， the proportion of oil red O-positive staining area， the collagen deposition fraction， and the levels of phosphorylated PI3K and AKT proteins， as well as the expression levels of PDGF and Caspase-3 proteins in liver tissue， were all significantly increased （P＜0.05）. The liver tissue showed severe pathological damage， characterized by an abundance of lipid droplets and pronounced collagen deposition. After the intervention with Met， the aforementioned quantitative indicators and pathological changes in rats were significantly improved in a dose- dependent manner （P＜0.05）. 740 Y-P could reverse the improvement effects of high dose of Met on the above indexes of rats （P＜ 0.05）. CONCLUSIONS Met can improve liver damage， and alleviate inflammatory reactions and liver fibrosis of NASH rats， the mechanism of which may be associated with inhibiting PI3K/AKT/PDGF signaling pathway.
