Li Yining, Chen Yulin, Zhang Hui, Chen Weidong, Pan Yan
Department of Nephrology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, People's Republic of China.
Diabetes Metab Syndr Obes. 2024 Oct 30;17:4091-4104. doi: 10.2147/DMSO.S492252. eCollection 2024.
The glucagon-like peptide-1 receptor agonist (GLP-1RA) is a pharmacological agent utilized for the treatment of diabetes, known for its significant reno protective effects. This study aims to investigate the impact of liraglutide, a representative GLP-1RA medication, on early endothelial dysfunction in diabetic rats and elucidate its underlying mechanisms.
The present study employed a high-fat, high-sugar diet in combination with a single intraperitoneal injection of streptozotocin (STZ) to establish an experimental rat model of diabetes. Subsequently, the therapeutic efficacy of liraglutide on renal injury in this model was evaluated using various doses.
Compared to the DKD rats, the rats treated with Liraglutide exhibited significant reductions in levels of blood glucose (Glu), serum creatinine (Scr), and blood urea nitrogen (BUN) (P < 0.05). Furthermore, there was a dose-dependent decrease in urinary protein levels, including 24-hour urinary protein excretion rate and microalbuminuria (m-ALB), with higher doses demonstrating more pronounced therapeutic effects (P <0.05). In addition, treatment with Liraglutide effectively improved glomerular and interstitial damage, and suppressed the expression of CD31, CD34, and VE-cadherin associated with endothelial cell injury (P < 0.05). Furthermore, Liraglutide administration significantly increased nitric oxide (NO) production (P < 0.05). Moreover, Liraglutide treatment resulted in decreased expression of vascular endothelial growth factor (VEGF), Delta-like ligand-4(Dll4), and Notch2 protein in the Notch2 signaling pathway (P < 0.05).
The findings indicate that Liraglutide has a substantial effect on decreasing urinary protein excretion and improving vascular microinflammation, thus alleviating endothelial dysfunction in diabetic nephropathy. This observed mechanism can be attributed to the inhibition of the Dll4/Notch2 signaling pathway.
胰高血糖素样肽-1受体激动剂（GLP-1RA）是一种用于治疗糖尿病的药物，以其显著的肾脏保护作用而闻名。本研究旨在探讨代表性GLP-1RA药物利拉鲁肽对糖尿病大鼠早期内皮功能障碍的影响，并阐明其潜在机制。
本研究采用高脂高糖饮食联合单次腹腔注射链脲佐菌素（STZ）建立实验性糖尿病大鼠模型。随后，使用不同剂量评估利拉鲁肽对该模型肾损伤的治疗效果。
与糖尿病肾病（DKD）大鼠相比，接受利拉鲁肽治疗的大鼠血糖（Glu）、血清肌酐（Scr）和血尿素氮（BUN）水平显著降低（P<0.05）。此外，尿蛋白水平呈剂量依赖性降低，包括24小时尿蛋白排泄率和微量白蛋白尿（m-ALB），较高剂量显示出更显著的治疗效果（P<0.05）。此外，利拉鲁肽治疗有效改善了肾小球和间质损伤，并抑制了与内皮细胞损伤相关的CD31、CD34和血管内皮钙黏蛋白的表达（P<0.05）。此外，给予利拉鲁肽显著增加了一氧化氮（NO）的产生（P<0.05）。此外，利拉鲁肽治疗导致Notch2信号通路中血管内皮生长因子（VEGF）、Delta样配体-4（Dll4）和Notch2蛋白的表达降低（P<0.05）。
研究结果表明，利拉鲁肽对减少尿蛋白排泄和改善血管微炎症有显著作用，从而减轻糖尿病肾病中的内皮功能障碍。观察到的这种机制可归因于对Dll4/Notch2信号通路的抑制。
