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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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

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

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