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格列齐特和槲皮素联合治疗对 STZ 诱导的糖尿病大鼠的保护作用。

New combination therapy of gliclazide and quercetin for protection against STZ-induced diabetic rats.

机构信息

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.

Department of Medicinal and Pharmaceutical Chemistry, Pharmacology Group, National Research Centre, Cairo, Egypt.

出版信息

Life Sci. 2020 Apr 15;247:117458. doi: 10.1016/j.lfs.2020.117458. Epub 2020 Feb 21.

Abstract

AIMS

The use of natural agents with anti-diabetic effect in combination therapy adds further positive clinical implications in the management of diabetes mellitus. Interestingly, quercetin is one of the most potent naturally occurring antioxidant which possesses various pharmacological actions including anti-diabetic effect. Thus, this research was conducted to assess the efficiency of a new combination from gliclazide and quercetin on glycemic control as well as pancreatic islets and beta cells in STZ-experimental model of diabetes.

MAIN METHODS

Diabetes has been induced by a single intraperitoneal injection of streptozotocin (STZ; 45 mg/kg) in adult male Wistar rats. For 3 consecutive weeks, diabetic rats were given orally either gliclazide (10 mg/kg), quercetin (50 mg/kg), or their combination. At the end of the experiment, histological, immunohistochemical and morphometrical examination of pancreatic tissues was performed. Furthermore, the changes in glucose metabolism, lipid profile, oxidative and inflammatory status were evaluated.

KEY FINDINGS

Treatment with gliclazide alone decreased serum glucose, total cholesterol, triglycerides, malondialdehyde, tumor necrosis factor-alpha and nuclear factor kappa-Beta while increased serum C-peptide, superoxide dismutase, reduced glutathione and adiponectin levels. Combined administration of quercetin with gliclazide markedly augmented serum superoxide dismutase and reduced glutathione more than gliclazide alone and normalized all the above-mentioned parameters. Besides, this combination therapy restored immunostaining intensity, number of pancreatic islets and beta cells along with its area and perimeter.

SIGNIFICANCE

Based on the aforementioned results, this combination could be considered a promising one in diabetes mellitus management.

摘要

目的

将具有抗糖尿病作用的天然药物与联合疗法一起使用,为糖尿病的治疗带来了更多积极的临床意义。有趣的是,槲皮素是最有效的天然抗氧化剂之一,具有多种药理作用,包括抗糖尿病作用。因此,本研究旨在评估格列齐特和槲皮素的新组合对 STZ 诱导的糖尿病动物模型的血糖控制以及胰岛和β细胞的作用。

主要方法

通过单次腹腔注射链脲佐菌素(STZ;45mg/kg)诱导成年雄性 Wistar 大鼠糖尿病。连续 3 周,糖尿病大鼠分别口服给予格列齐特(10mg/kg)、槲皮素(50mg/kg)或两者的组合。实验结束时,对胰腺组织进行组织学、免疫组织化学和形态计量学检查。此外,还评估了葡萄糖代谢、血脂谱、氧化和炎症状态的变化。

主要发现

单独使用格列齐特治疗可降低血清葡萄糖、总胆固醇、甘油三酯、丙二醛、肿瘤坏死因子-α和核因子 kappa-Beta,同时增加血清 C 肽、超氧化物歧化酶、还原型谷胱甘肽和脂联素水平。与格列齐特单独给药相比,联合给予槲皮素可显著增加血清超氧化物歧化酶和还原型谷胱甘肽水平,并使所有上述参数正常化。此外,这种联合治疗还恢复了胰岛和β细胞的免疫染色强度、数量及其面积和周长。

意义

基于上述结果,这种联合疗法可能被认为是糖尿病治疗的一种有前途的方法。

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