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柚皮素对果糖-链脲佐菌素糖尿病大鼠模型长期高血糖状态下血管变化的影响

Effects of naringenin on vascular changes in prolonged hyperglycaemia in fructose-STZ diabetic rat model.

作者信息

Zaidun Nurul Hannim, Sahema Zar Chi Thent, Mardiana Abdul Aziz, Santhana Raj L, Latiff Azian Abd, Syed Ahmad Fuad Syed Baharom

机构信息

Faculty of Medicine, Universiti Teknologi MARA (UiTM).

Institute of Medical Research.

出版信息

Drug Discov Ther. 2019;13(4):212-221. doi: 10.5582/ddt.2019.01034.

Abstract

Chronic uncontrolled hyperglycaemia leads to increased oxidative stress and lipid peroxidation resulting in vascular complications and accelerates the progression of diabetic atherosclerosis. Though varieties of modern drugs used in the treatment of diabetes, the complications of diabetes are increasing. Naringenin (NG), has been reported to have potent antioxidant and anti-atherosclerotic properties. However, the effects of NG as vasculoprotective agent in prolonged hyperglycaemia are not well documented. Thus, this study was aimed to determine the effect of NG against vascular changes after prolonged hyperglycaemia in a diabetic rat model. Thirty adult male Sprague-Dawley rats were induced with fructose and streptozotocin to develop the diabetic rat model. After 4 weeks, the rats were randomly divided into 5 groups each group consisting of 6 animals: control, control treated with NG, non-treated diabetes mellitus (DM), DM treated with NG and metformin-treated DM. The treatment with NG (50 mg/kg) and metformin were continued for 5 weeks. The results showed that consumption of NG at 4 weeks post diabetic did not improved blood sugar, blood pressure and serum lipid profile. However, NG did significantly improve oxidative stress parameters in the aortic tissue like malondialdehyde (MDA). Analysis through light microscopy and transmission electron microscope (TEM) reverted the histological changes caused by prolonged hyperglycaemia. The findings thus demonstrated that introduction of NG after prolonged exposure to hyperglycaemia improved the vascular deterioration in diabetic group by decreasing oxidative stress evident by the reduced in the lipid peroxidation activity. Thus, this study showed the potential use of NG as adjunct in managing the diabetic condition during late presentation.

摘要

慢性未控制的高血糖会导致氧化应激和脂质过氧化增加,从而引发血管并发症,并加速糖尿病动脉粥样硬化的进展。尽管用于治疗糖尿病的现代药物种类繁多,但糖尿病并发症仍在增加。柚皮素(NG)据报道具有强大的抗氧化和抗动脉粥样硬化特性。然而,NG作为血管保护剂在长期高血糖中的作用尚未得到充分记录。因此,本研究旨在确定NG对糖尿病大鼠模型长期高血糖后血管变化的影响。30只成年雄性Sprague-Dawley大鼠用果糖和链脲佐菌素诱导建立糖尿病大鼠模型。4周后,将大鼠随机分为5组,每组6只动物:对照组、用NG治疗的对照组、未治疗的糖尿病(DM)组、用NG治疗的DM组和用二甲双胍治疗的DM组。用NG(50mg/kg)和二甲双胍治疗持续5周。结果显示,糖尿病后4周服用NG并未改善血糖、血压和血脂谱。然而,NG确实显著改善了主动脉组织中的氧化应激参数,如丙二醛(MDA)。通过光学显微镜和透射电子显微镜(TEM)分析逆转了长期高血糖引起的组织学变化。这些发现表明,在长期暴露于高血糖后引入NG可通过降低脂质过氧化活性所显示的氧化应激来改善糖尿病组的血管恶化。因此,本研究表明NG在糖尿病晚期治疗中作为辅助药物的潜在用途。

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