基于TGF-β<sub>1</sub>/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

doi:10.3969/j.issn.1006-6233.2024.11.010

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摘要 目的:探讨基于转化生长因子-β(TGF-β₁)/Smad信号通路度拉糖肽(Dula)对2型糖尿病肾病(T2DN)大鼠肾损伤的影响。方法:随机选取10只大鼠作为Control组,其余大鼠构建T2DN模型,将建模成功的大鼠随机分为T2DN组、L-Dula、M-Dula、H-Dula,Dula+SRI-011381每组10只。测定各组大鼠体质量;采用全自动生化分析仪检测T2DN大鼠血清中ALB、Scr、BUN、TG、TC含量;HE和PAS染色观察T2DN大鼠肾组织病理改变;Western blot检测T2DN大鼠肾组织中TGF-β₁、Smad2/3、Smad7蛋白的表达。结果:T2DN组肾小球肥大,基底膜增厚,囊腔萎缩,间质炎性细胞浸润,肾小球内糖原沉积增多,可见红色染色区域,24h尿蛋白、Scr、BUN、FBG、TG、TC、TGF-β₁、Smad2/3表达高于Control组,体质量、Smad7表达低于Control组(P<0.05);L-Dula、M-Dula、H-Dula组肾小球和肾小管病变程度均依次减轻,红色染色区域依次减少,24h尿蛋白、Scr、BUN、FBG、TG、TC、TGF-β₁、Smad2/3表达低于T2DN组,体质量、Smad7表达高于T2DN组(P<0.05);Dula+SRI-011381组肾小球和肾小管病变加重、红色染色区域增大、24h尿蛋白、Scr、BUN、FBG、TG、TC、TGF-β₁、Smad2/3表达高于H-Dula组,体质量、Smad7表达低于H-Dula组(P<0.05)。结论:Dula可能通过抑制TGF-β₁/Smad信号通路抑制T2DN大鼠肾损伤。

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关键词 ： 2型糖尿病, 转化生长因子-β, Smad, 度拉糖肽, 肾损伤

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 Dulaglutide), 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 hypertrophy, 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.

Key words： Type 2 diabetes mellitus Transforming growth factor-β Smad Dulaglutide Renal injury

基金资助:河北省卫生健康委员会资助项目,(编号:20232149)

引用本文:

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): 1815-1819.
KONG Wubao, WANG Xiaoyun, NIU YueLong, et al. Effect and Mechanism of Dulaglutide on Kidney Injury in Rats with Type 2 Diabetic Nephropathy Based on the TGF-β₁/Smad Signaling Pathway. HeBei Med, 2024, 30(11): 1815-1819.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2024.11.010 或 http://www.hbyxzzs.cn/CN/Y2024/V30/I11/1815

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