Curcumin attenuates hyperglycaemia-mediated AMPK activation and oxidative stress in cerebrum of streptozotocin-induced diabetic rat

Curcumin attenuates hyperglycaemia-mediated AMPK activation and oxidative stress in cerebrum of streptozotocin-induced diabetic rat
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DOI:
10.3109/10715762.2011.579121
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发表时间:
2011-07-01
影响因子:
3.3
通讯作者:
Kodama, Makoto
Kodama, Makoto
中科院分区:
生物学3区
文献类型:
--
作者:
Lakshmanan, Arun Prasath;Watanabe, Kenichi;Kodama, Makoto

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氧化应激与糖尿病脑病(DE)的发病机制密切相关。大量研究表明,在各种疾病(包括糖尿病相关的脑部疾病)中,氧化应激与 AMPK 激活之间存在密切关系。由于姜黄素具有强大的抗氧化特性,本研究研究了其对 DE 大鼠高血糖介导的氧化应激和 AMPK 激活的影响。通过单次腹腔注射链脲佐菌素(STZ-55 mg/kg BW)诱发糖尿病。然后,糖尿病大鼠口服姜黄素(100 mg/kg BW)或载体,持续 8 周。与对照组相比,糖尿病大鼠的大脑中 AdipoR1、p-AMPK α α 1、Tak1、GLUT4、NADPH 氧化酶亚基、caspase-12 和 3-NT 的蛋白表达上调,并且脂质过氧化增加,并且除了 AdipoR1 表达增加外,所有这些效应在姜黄素治疗后均显着减弱。这些结果为姜黄素对高血糖介导的 DE 的有益作用提供了新的见解,DE 是通过下调与其抗氧化特性相关的 AMPK 介导的糖异生而产生的。
Oxidative stress has been strongly implicated in the pathogenesis of diabetic encephalopathy (DE). Numerous studies have demonstrated a close relationship between oxidative stress and AMPK activation in various disorders, including diabetes-related brain disorders. Since curcumin has powerful antioxidant properties, this study investigated its effects on hyperglycaemia-mediated oxidative stress and AMPK activation in rats with DE. Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ-55 mg/kg BW). The diabetic rats were then orally administered curcumin (100 mg/kg BW) or vehicle for 8 weeks. The cerebra of the diabetic rats displayed upregulated protein expression of AdipoR1, p-AMPK alpha alpha 1, Tak1, GLUT4, NADPH oxidase sub-units, caspase-12 and 3-NT and increased lipid peroxidation in comparison with the controls and all of these effects were significantly attenuated with curcumin treatment, except for the increase in AdipoR1 expressions. These results provide a new insight into the beneficial effects of curcumin on hyperglycaemia-mediated DE, which are produced through the down-regulation of AMPK-mediated gluconeogenesis associated with its anti-oxidant property.