Mastrocola R, Restivo F, Vercellinatto I, Danni O, Brignardello E, Aragno M, Boccuzzi G
Department of Experimental Medicine and Oncology, Section of General Pathology, Corso Raffaello 30, University of Turin, 10125 Turin, Italy.
J Endocrinol. 2005 Oct;187(1):37-44. doi: 10.1677/joe.1.06269.
Diabetic encephalopathy, characterized by impaired cognitive functions and neurochemical and structural abnormalities, may involve direct neuronal damage caused by intracellular glucose. The study assesses the direct effect of chronic hyperglycemia on the function of brain mitochondria, the major site of reactive species production, in diabetic streptozotocin (STZ) rats. Oxidative stress plays a central role in diabetic tissue damage. Alongside enhanced reactive oxygen species (ROS) levels, both nitric oxide (NO) levels and mitochondrial nitric oxide synthase expression were found to be increased in mitochondria, whereas glutathione (GSH) peroxidase activity and manganese superoxide dismutase protein content were reduced. GSH was reduced and GSH disulfide (GSSG) was increased in STZ rats. Oxidative and nitrosative stress, by reducing the activity of complexes III, IV and V of the respiratory chain and decreasing ATP levels, might contribute to mitochondrial dysfunction. In summary, this study offers fresh evidence that, besides the vascular-dependent mechanisms of brain dysfunction, oxidative and nitrosative stress, by damaging brain mitochondria, may cause direct injury of neuronal cells.
糖尿病性脑病以认知功能受损以及神经化学和结构异常为特征，可能涉及细胞内葡萄糖引起的直接神经元损伤。该研究评估了慢性高血糖对糖尿病链脲佐菌素（STZ）大鼠脑线粒体功能的直接影响，脑线粒体是活性物质产生的主要部位。氧化应激在糖尿病组织损伤中起核心作用。除了活性氧（ROS）水平升高外，还发现线粒体中的一氧化氮（NO）水平和线粒体一氧化氮合酶表达均增加，而谷胱甘肽（GSH）过氧化物酶活性和锰超氧化物歧化酶蛋白含量降低。STZ大鼠体内GSH减少而氧化型谷胱甘肽（GSSG）增加。氧化应激和亚硝化应激通过降低呼吸链复合物III、IV和V的活性以及降低ATP水平，可能导致线粒体功能障碍。总之，本研究提供了新的证据，表明除了脑功能障碍的血管依赖性机制外，氧化应激和亚硝化应激通过损害脑线粒体，可能导致神经元细胞的直接损伤。
