Department of Endocrinology and Metabolism, Nanping First Hospital Affiliated to Fujian Medical University, Nanping, Fujian, China.
Department of Cardiovascular Medicine, Nanping First Hospital Affiliated to Fujian Medical University, Nanping, Fujian, China.
Clin Exp Pharmacol Physiol. 2024 Dec;51(12):e70003. doi: 10.1111/1440-1681.70003.
Diabetic nephropathy (DN) is a severe renal disorder that arises as a complication of diabetes. Liraglutide, an analogue of a glucagon-like peptide 1 (GLP-1) receptor agonist, has been shown to decrease diabetes-caused renal damage. Nevertheless, the complete understanding of the roles and mechanism remains unclear. In our study, diabetic rat models were created through a single intraperitoneal injection of streptozotocin (STZ). The level of fasting blood glucose, 24-h urine protein, serum creatinine (Scr) and blood urea nitrogen (BUN) were assessed. Periodic acid-Schiff (PAS) staining was applied to examine the pathological changes in renal tissues. Reactive oxygen species (ROS) formation was measured via dichloro-dihydro-fluorescein diacetate (DCFH-DA) probes. Western blot was conducted to examine the levels of oxidative stress-related and extracellular matrix (ECM)-associated proteins. The nuclear translocation of NRF2 was investigated through immunofluorescence and Western blot assays. We demonstrated that liraglutide attenuated DN-induced oxidative stress and ECM deposition in vitro and in vivo. Liraglutide exerted a reno-protective effect by promoting nuclear translocation of NRF2 in mesangial cells. ML385, an NRF2 inhibitor, counteracted the beneficial impact of liraglutide.
糖尿病肾病（DN）是一种严重的肾脏疾病，是糖尿病的并发症之一。利拉鲁肽是一种胰高血糖素样肽 1（GLP-1）受体激动剂类似物，已被证明可减少糖尿病引起的肾脏损伤。然而，其作用机制仍不完全清楚。在我们的研究中，通过单次腹腔注射链脲佐菌素（STZ）建立糖尿病大鼠模型。检测空腹血糖、24 小时尿蛋白、血清肌酐（Scr）和血尿素氮（BUN）水平。过碘酸希夫（PAS）染色观察肾组织病理变化。二氯二氢荧光素二乙酸酯（DCFH-DA）探针检测活性氧（ROS）形成。Western blot 检测氧化应激相关和细胞外基质（ECM）相关蛋白水平。免疫荧光和 Western blot 检测核转录因子 NRF2 的核转位。结果表明，利拉鲁肽在体内外减轻了 DN 诱导的氧化应激和 ECM 沉积。利拉鲁肽通过促进肾小球系膜细胞中 NRF2 的核转位发挥肾脏保护作用。NRF2 抑制剂 ML385 拮抗了利拉鲁肽的有益作用。
