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Combination of Captopril with Gliclazide Decreases Vascular and Renal Complications and Improves Glycemic Control in Rats with Streptozotocin- Induced Diabetes Mellitus
Endocrine, Metabolic & Immune Disorders - Drug Targets ( IF 1.9 ) Pub Date : 2021-05-31 , DOI: 10.2174/1871530320666200821160436
Sayed Mizar Metwally Mizar 1 , Magy Refaat Kozman 2 , Ali Ahmed Abo-Saif 3 , Basim Anwar Shehata Messiha 4
Affiliation  

Background: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.



中文翻译:

卡托普利与格列齐特联用可减少链脲佐菌素诱导的糖尿病大鼠的血管和肾脏并发症并改善血糖控制

背景:据报道,常见的抗高血压血管紧张素转换酶 (ACE) 抑制剂卡托普利在不同的实验模型中具有抗氧化和抗炎作用。糖尿病血管并发症源于血管内皮炎症和氧化应激增加以及由于血糖控制不佳导致血管壁中一氧化氮生物利用度降低。

目的:本研究旨在评估卡托普利和格列齐特在减少由细胞葡萄糖摄取减少和内皮一氧化氮代谢受损引起的糖尿病(DM)血管并发症中的作用,并检查联合用药对糖尿病肾并发症和血浆的影响。脂质谱。

方法:成年雄性 Wister 大鼠在使用链脲佐菌素(50 mg/kg,ip,腹腔注射)诱导 DM 后每天通过口服管饲法接受卡托普利(25 mg/kg/天)和/或格列齐特(10 mg/kg/天),持续 1 个月。一次)。测量了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)以及血浆脂质分布。此外,胸主动脉和肾组织的组织病理学检查,蛋白质印迹评估了胸主动脉中一氧化氮合酶(NOS)亚型的表达。

结果:卡托普利通过调节一氧化氮合酶显着改善血管结构和氧化应激,调节一氧化氮合成,并通过下调 TNF-α 减少炎症,降低收缩压和舒张压,改善糖尿病大鼠的血脂谱. 格列齐特增加血清胰岛素和降低血清葡萄糖,以及其抗氧化和抗炎作用。

结论:卡托普利显示出对 DM 血管并发症的有希望的保护作用,至少是通过一氧化氮调节作用、抗氧化作用和抗炎活性,这些作用出现在生化和组织病理学发现、脂质特征、肾功能和结构改善中。将格列齐特与卡托普利联合使用,通过增强血糖控制和增加抗氧化和抗炎特性,比单独使用卡托普利更能产生相加作用。

更新日期:2021-07-14
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