疑难病杂志2025，Vol.24Issue(9)：1115-1121,1131,8.DOI:10.3969/j.issn.1671-6450.2025.09.017
罗沙司他对2型糖尿病大鼠糖脂代谢、肝功能、炎性反应、肝脏脂肪蓄积及TLR4/NF-κB通路的影响
Effects of roxadustat on glycolipid metabolism and liver injury in type 2 diabetic rats via TLR4/NF-κB pathway
摘要
Abstract
Objective To explore roxadustat's effects on diabetes-associated metabolic/liver dysfunction.Methods The experiments were conducted at the Animal Laboratory of the Changjiang Shipping General Hospital from August 2024 to January 2025.T2DM rats were induced by feeding high fat and high sugar feed and intraperitoneal injection of streptozoto-cin.60 T2DM rats were randomly divided into:model group,ROX low dose group(12.5 mg/kg),ROX medium dose group(25 mg/kg),ROX high dose group(50 mg/kg),metformin hydrochloride group(200 mg/kg),12 animals in each group;anoth-er 12 normal rats were given normal feed for 8 weeks and normal saline was injected into the abdominal cavity as healthy con-trol group;each group was given corresponding intervention for 8 weeks.Automatic biochemical analyzer was used to detect the blood glucose,blood lipids and liver function indexes of rats,and the liver index was determined.Serum inflammatory fac-tors were detected by enzyme-linked immunosorbent assay.Liver tissue histopathology and fat accumulation were observed by hematoxylin-eosin staining and oil red O staining.The expression of TLR4/NF-κB pathway protein in liver tissue was detected by western blot.Results Compared with healthy control group,the liver tissue structure of rats in model group was disorder-ed,the morphology of liver cells was changed,lipid vacuoles and large orange red areas appeared,and the degree of fat accu-mulation was serious;serum fasting blood glucose(FPG),fasting insulin(FINS),insulin resistance index(HOMA-IR),total cholesterol(TC),triacylglycerol(TG),low density lipoprotein-cholesterol(LDL-C),alanine aminotransferase(ALT),aspartate aminotransferase(AST),liver index,C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),the ex-pressions of TLR4,phosphorylated-NF-κB p65(p-NF-κB p65)/NF-κB p65 protein in liver tissue were increased,and high density lipoprotein-cholesterol(HDL-C)was decreased(t/P=12.983/＜0.001,10.640/＜0.001,19.194/＜0.001,16.195/＜0.001,17.406/＜0.001,17.660/＜0.001,14.805/＜0.001,13.273/＜0.001,9.039/＜0.001,10.590/＜0.001,16.086/＜0.001,20.255/＜0.001,22.789/＜0.001,14.976/＜0.001,9.824/＜0.001).Compared with model group,the rats of ROX low,medium,and high dose groups and metformin hydrochloride group showed significant improvement in liver tissue lesions,reduced orange red area in liver cells,decreased degree of fat accumulation;serum FPG,FINS,HOMA-IR,TC,TG,LDL-C,ALT,AST,liver index,CRP,TNF-α,IL-6,TLR4,p-NF-κB p65/NF-κB p65 protein expression in liver tissue were decreased,while HDL-C was increased(F/P=37.001/＜0.001,34.685/＜0.001,99.532/＜0.001,101.881/＜0.001,120.663/＜0.001,105.021/＜0.001,61.833/＜0.001,48.872/＜0.001,37.652/＜0.001,36.541/＜0.001,69.113/＜0.001,86.194/＜0.001,66.174/＜0.001,63.913/＜0.001,27.611/＜0.001).The degree of decrease in serum FPG,FINS,HOMA-IR,TC,TG,LDL-C,ALT,AST,liver index,CRP,TNF-α,IL-6,liver tis-sue TLR4,p-NF-κB p65/NF-κB p65 protein expression in ROX low,medium,high dose groups and the degree increase in HDL-C were dose-dependent(F/P=19.952/＜0.001,18.082/＜0.001,48.212/＜0.001,63.192/＜0.001,88.165/＜0.001,66.031/＜0.001,31.735/＜0.001,27.221/＜0.001,22.784/＜0.001,22.072/＜0.001,40.682/＜0.001,48.306/＜0.001,39.842/＜0.001,44.825/＜0.001,14.002/＜0.001).The liver tissue structure and morphology of rats in ROX high dose group and metformin hydrochlo-ride group were similar and tended to be normal,the orange area of liver cells was similar,the degree of fat accumulation was most significantly reduced,and there was no statistical significance in the glucose and lipid metabolism indexes,liver function indexes and liver index,inflammatory factors,and TLR4/NF-κB pathway protein expression in liver tissue(P＞0.05).Conclu-sion Roxadustat ameliorates diabetic liver injury by modulating glucose metabolism and TLR4/NF-κB signaling.关键词
2型糖尿病/罗沙司他/糖脂代谢/肝脏脂肪蓄积/Toll样受体4/核转录因子-κB通路/大鼠Key words
Type 2 diabetes/Roxadustat/Glucolipid metabolism/Liver fat accumulation/TLR4/NF-κB pathway/Rats分类
医药卫生引用本文复制引用
石秀祯,何艳,徐申,郭爱莉,付锴,谭金枚..罗沙司他对2型糖尿病大鼠糖脂代谢、肝功能、炎性反应、肝脏脂肪蓄积及TLR4/NF-κB通路的影响[J].疑难病杂志,2025,24(9):1115-1121,1131,8.基金项目
湖北省卫生健康委科研立项项目(WJ2023M024) （WJ2023M024）
长航局科技项目(202210005) Hubei Health Commission Research Project(WJ2023M024) （202210005）
Science and Technology Project of Yangtze River Navigation Bureau(202210005) （202210005）
