孟鲁司特是一种半胱氨酰白三烯受体 (CysLTR)1 拮抗剂，正在成为减少糖尿病并发症的一种有吸引力的策略；然而，它在主动脉和睾丸组织中的作用尚不清楚。本研究探讨了孟鲁司特拮抗 CysLTR1 对糖尿病引起的主动脉和睾丸损伤中 Toll 样受体 (TLR)4 和核因子 kappa B (NF-κB) 通路的影响。 成年雄性 Sprague-Dawley 大鼠用链脲佐菌素致糖尿病（STZ，55 毫克/千克）。此后，链脲佐菌素诱导的糖尿病 (SD) 大鼠服用孟鲁司特（10 和 20 毫克/公斤，口服）8 周。对血糖、血清丙二醛 (MDA)、炎症标志物和组织病理学进行了评估。孟鲁司特对糖尿病并发症具有预防作用，血清 MDA 水平对 STZ 诱导的氧化应激变化的改善作用就证明了这一点。此外，孟鲁司特使主动脉和睾丸的 CysLTR1、TLR4 和 NF-κB 水平显着降低，随后 NOD 样受体家族 Pyrin 结构域 (NLRP)3、Caspase 1、白细胞介素 (IL) 的水平降低-1β、IL-6、单核细胞趋化蛋白 (MCP)-1 和肿瘤坏死因子 (TNF)-α。此外，孟鲁司特的给药会刺激自噬，p62/Sequestosome (SQSTM)1 水平降低表明。最后，组织病理学证明，孟鲁司特保护作用导致整个主动脉壁厚度正常，内膜规则，主动脉平滑肌纤维轻度空泡化，生精小管尺寸增加，睾丸生精增加。孟鲁司特之所以能够对抗糖尿病引起的主动脉和睾丸损伤，是由于其抗氧化、抗炎和自噬刺激特性。版权所有 © 2023 Elsevier B.V. 保留所有权利。

Montelukast, a cysteinyl leukotriene receptor (CysLTR)1 antagonist, is emerging as an attractive strategy to curtail diabetic complications; however, its role in aortic and testicular tissues is unknown. This study investigated the effect of CysLTR1 antagonism by montelukast on toll-like receptor (TLR)4 and nuclear factor kappa B (NF-κB) pathways in diabetes-induced aortic and testicular injury.Adult male Sprague-Dawley rats were made diabetic with Streptozotocin (STZ, 55 mg/kg). Following this, Streptozotocin-induced diabetic (SD) rats were administered montelukast (10 and 20 mg/kg, orally) for 8 weeks. Blood glucose, serum malondialdehyde (MDA), inflammatory markers, and histopathology were evaluated.Montelukast showed protection against diabetic complications, as evidenced by the ameliorative effect against STZ-induced alterations in oxidative stress as indicated by serum MDA levels. Moreover, montelukast conferred a significant decrease in the aortic and testicular levels of CysLTR1, TLR4, and NF-κB with a subsequent decrease in the levels of NOD-like receptor family pyrin domain containing (NLRP)3, caspase 1, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α. Additionally, administration of montelukast resulted in autophagy stimulation, as shown by decreased p62/Sequestosome (SQSTM)1 levels. Finally, montelukast protection resulted in normal thickness of whole aortic wall, regular tunica (t.) intima, mild vacuolation of smooth muscle fibers in aorta, increased size of seminiferous tubules, and increased spermatogenesis in testis as demonstrated by histopathology.The protective effect of montelukast against diabetes-induced aortic and testicular injury is due to its antioxidant, anti-inflammatory, and autophagy stimulation characteristics.Copyright © 2023 Elsevier B.V. All rights reserved.