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链脲佐菌素诱导的糖尿病大鼠下丘脑氧化应激增加和线粒体损伤:印度人参的抗氧化作用

Increase in oxidative stress and mitochondrial impairment in hypothalamus of streptozotocin treated diabetic rat: Antioxidative effect of Withania somnifera.

作者信息

Parihar P, Shetty R, Ghafourifar P, Parihar M S

机构信息

Vikram University School of Studies in Zoology & Biotechnology Ujjain India.

Tri-State Institute of Pharmaceutical Sciences Huntington USA.

出版信息

Cell Mol Biol (Noisy-le-grand). 2016 Jan 22;62(1):73-83.

PMID:26828992
Abstract

Hypothalamus, the primary brain region for glucose sensing, is severely affected by oxidative stress in diabetes mellitus. Oxidative stress in this region of brain may cause severe impairment in neuronal metabolic functions. Mitochondria are prominent targets of oxidative stress and the combination of increased oxidative stress and mitochondrial dysfunctions may further decline hypothalamic neuronal functions. In the present study we examined the oxidative damage response, antioxidative responses and mitochondrial membrane permeability transition in hypothalamus of streptozotocin-treated diabetic rats. Our results show that streptozotocin significantly increases hypothalamic lipid peroxidation, protein carbonyl content while glutathione peroxidase and reduced glutathione were declined. Mitochondrial impairment marked by an increase in mitochondrial membrane permeabilization was seen following streptozotocin treatment in the hypothalamus. The oral administration of Withania somnifera root extract stabilized mitochondrial functions and prevented oxidative damage in the hypothalamus of diabetic rat. These findings suggest an increase in the oxidative stress and decline in antioxidative responses in the hypothalamus of streptozotocin treated diabetic rats. Withania somnifera root extract was found useful in reducing oxidative stress and mitochondrial impairment in hypothalamus of diabetic rat.

摘要

下丘脑是大脑中感知葡萄糖的主要区域,在糖尿病中受到氧化应激的严重影响。大脑该区域的氧化应激可能导致神经元代谢功能严重受损。线粒体是氧化应激的主要靶点,氧化应激增加与线粒体功能障碍相结合可能会进一步降低下丘脑神经元功能。在本研究中,我们检测了链脲佐菌素诱导的糖尿病大鼠下丘脑的氧化损伤反应、抗氧化反应和线粒体膜通透性转换。我们的结果表明,链脲佐菌素显著增加下丘脑脂质过氧化、蛋白质羰基含量,同时谷胱甘肽过氧化物酶和还原型谷胱甘肽含量下降。链脲佐菌素处理后,下丘脑出现以线粒体膜通透性增加为特征的线粒体损伤。口服睡茄根提取物可稳定线粒体功能,并防止糖尿病大鼠下丘脑的氧化损伤。这些发现表明,链脲佐菌素处理的糖尿病大鼠下丘脑氧化应激增加,抗氧化反应下降。发现睡茄根提取物有助于降低糖尿病大鼠下丘脑的氧化应激和线粒体损伤。

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