河北医学2024，Vol.30Issue(11)：1815-1820,6.DOI:10.3969/j.issn.1006-6233.2024.11.010
基于TGF-β1/Smad信号通路探究度拉糖肽对2型糖尿病肾病大鼠肾损伤的影响及机制
Effect and Mechanism of Dulaglutide on Kidney Injury in Rats with Type 2 Diabetic Nephropathy Based on the TGF-β1/Smad Signaling Pathway
摘要
Abstract
Objective:To investigate the effect of dulaglutide(Dula)on kidney injury in rats with type 2 diabetic nephropathy(T2DN)and explore the underlying mechanism based on the transforming growth factor-β1(TGF-β1)/Smad signaling pathway.Methods:A total of 10 rats were randomly selected as the Control group,while the remaining rats were used to establish a T2DN model.Successfully modeled rats were divided into five groups:T2DN group,L-Dula group(low-dose Dulaglutide),M-Dula group(medium-dose Dula-glutide),H-Dula group(high-dose Dulaglutide),and Dula+SRI-011381 group,with 10 rats per group.The body weight of each group was measured.Serum levels of albumin(ALB),serum creatinine(Scr),blood urea nitrogen(BUN),triglycerides(TG),and total cholesterol(TC)were detected using an automatic biochemical analyzer.Hematoxylin-eosin(HE)and periodic acid-Schiff(PAS)staining were employed to observe pathological changes in kidney tissues.Western blotting was used to detect the expression of TGF-β1,Smad2/3,and Smad7 proteins in the kidney tissue of T2DN rats.Results:In the T2DN group,glomerular hy-pertrophy,thickened basement membranes,shrunken cavities,inflammatory cell infiltration in the interstitial region,and increased glycogen deposition in the glomeruli were observed.Red-stained areas were visible,and the levels of 24-hour urinary protein,Scr,BUN,fasting blood glucose(FBG),TG,TC,TGF-β1,and Smad2/3 were significantly higher,while body weight and Smad7 expression were lower than in the Control group(P<0.05).The severity of glomerular and tubular lesions decreased progressively from the L-Dula to the H-Dula group,with a reduction in red-stained areas.Levels of 24-hour urinary protein,Scr,BUN,FBG,TG,TC,TGF-β1,and Smad2/3 were lower in the Dula-treated groups compared to the T2DN group,and body weight and Smad7 expression were higher(P<0.05).In the Dula+SRI-011381 group,glomerular and tubular damage worsened,with larger red-stained areas,higher levels of 24-hour urinary protein,Scr,BUN,FBG,TG,TC,TGF-β1,and Smad2/3,and lower body weight and Smad7 expression compared to the H-Dula group(P<0.05).Conclusion:Dulaglutide may inhibit kidney injury in T2DN rats by suppressing the TGF-β1/Smad signaling pathway.关键词
2型糖尿病/转化生长因子-β/Smad/度拉糖肽/肾损伤Key words
Type 2 diabetes mellitus/Transforming growth factor-β/Smad/Dulaglutide/Renal injury引用本文复制引用
孔五宝,王晓蕴,牛跃龙,陈伟,常珊珊,邢立勇..基于TGF-β1/Smad信号通路探究度拉糖肽对2型糖尿病肾病大鼠肾损伤的影响及机制[J].河北医学,2024,30(11):1815-1820,6.基金项目
河北省卫生健康委员会资助项目,(编号:20232149) （编号:20232149）
