Department of Pharmacology and Toxicology, Faculty of Pharmacy, Fayoum University, Fayoum, Egypt.
Department of Clinical Pharmacy, Faculty of Pharmacy, Misr University for Science and Technology, Egypt.
Endocr Metab Immune Disord Drug Targets. 2021;21(6):1096-1106. doi: 10.2174/1871530320666200821160436.
The common antihypertensive angiotensin-converting enzyme (ACE) inhibitor captopril was reported to possess anti-oxidant and anti-inflammatory effects in different experimental models. Diabetic vascular complications arise from increased vascular endothelial inflammation and oxidative stress as well as decreased nitric oxide bioavailability in the vessel walls due to poor glycemic control.
This study aimed to evaluate the role of captopril and gliclazide in decreasing diabetes mellitus (DM) vascular complications caused by decreased cellular glucose uptake and impaired endothelial nitric oxide metabolism, as well as examine the effects of the combination on diabetic renal complication and plasma lipid profile.
Adult male Wister rats received captopril (25 mg/kg/day) and/or gliclazide (10 mg/kg/- day) by oral gavage daily for one month after induction of DM using streptozotocin (50 mg/kg, i.p., once). Serum glucose and insulin levels, inflammatory mediators like TNF-α, oxidative stress biomarkers like glutathione and nitric oxide, and plasma lipid profile were measured. Besides, histopathological examination of the thoracic aorta and kidney tissues, Western blot assessed the expression of nitric oxide synthase (NOS) subtypes in the thoracic aorta.
Captopril significantly improved vascular architecture and oxidative stress and modulated nitric oxide synthesis via regulation of nitric oxide synthases, as well as decreased inflammation via down-regulating TNF-α, decreased systolic and diastolic blood pressure, and improved serum lipid profile in diabetic rats. Gliclazide increased serum insulin and decreased serum glucose, as well as its anti-oxidant and anti-inflammatory effects.
Captopril showed a promising protective effect against DM vascular complications, at least via nitric oxide modulating effect, anti-oxidant effect, and anti-inflammatory activity that appeared in biochemical and histopathological findings, lipid profile, renal function, and architecture improvements. Combining gliclazide with captopril gives an additive effect through enhanced glycemic control and increased anti-oxidant and anti-inflammatory properties above captopril alone.
血管紧张素转换酶（ACE）抑制剂卡托普利是一种常用的降压药，在不同的实验模型中被报道具有抗氧化和抗炎作用。糖尿病血管并发症是由于血管内皮炎症和氧化应激增加以及血管壁一氧化氮生物利用度降低引起的，这是由于血糖控制不佳所致。
本研究旨在评估卡托普利和格列齐特在降低糖尿病（DM）血管并发症中的作用，这些并发症是由细胞葡萄糖摄取减少和内皮一氧化氮代谢受损引起的，并研究联合用药对糖尿病肾脏并发症和血浆脂质谱的影响。
成年雄性 Wister 大鼠在链脲佐菌素（50mg/kg，ip，一次）诱导 DM 后，通过口服灌胃每天给予卡托普利（25mg/kg/天）和/或格列齐特（10mg/kg/-天）一个月。测量血清葡萄糖和胰岛素水平、炎症介质如 TNF-α、氧化应激生物标志物如谷胱甘肽和一氧化氮以及血浆脂质谱。此外，还对胸主动脉和肾脏组织进行了组织病理学检查，Western blot 评估了胸主动脉中一氧化氮合酶（NOS）亚型的表达。
卡托普利通过调节一氧化氮合酶显著改善了血管结构和氧化应激，并调节了一氧化氮的合成，同时通过下调 TNF-α减少了炎症，降低了收缩压和舒张压，并改善了糖尿病大鼠的血清脂质谱。格列齐特增加了血清胰岛素并降低了血清葡萄糖，同时还具有抗氧化和抗炎作用。
卡托普利对 DM 血管并发症具有有前途的保护作用，至少通过生化和组织病理学发现、脂质谱、肾功能和结构改善中观察到的调节一氧化氮、抗氧化和抗炎作用。与卡托普利联合使用格列齐特可通过增强血糖控制和增加抗氧化和抗炎特性产生附加效果，优于单独使用卡托普利。
