标题：Protective Effects of Grape Seed Proanthocyanidin Extracts on Cerebral Cortex of Streptozotocin-Induced Diabetic Rats through Modulating AGEs/RAGE/NF-κB Pathway
期刊名称：Journal of Nutritional Science and Vitaminology
印刷版ISSN：0301-4800
电子版ISSN：1881-7742
出版年度：2010
卷号：56
期号：2
页码：87-97
DOI：10.3177/jnsv.56.87
出版社：Center for Academic Publications Japan
摘要：Diabetic encephalopathy is a severe complication in patients with long-term hyperglycemia. Oxidative stress is thought to be closely implicated in this disorder, so in this study, we examined whether grape seed proanthocyanidin extract (GSPE), a naturally occurring antioxidant derived from grape seeds, could reduce the injuries in the cerebral cortex of diabetic rats by modulating advanced glycation end products (AGEs)/the receptor for AGEs (RAGE)/nuclear factor-kappa B p65 (NF-κB p65) pathway, which is crucial in oxidative stress. Body weight and serum AGEs were tested; cerebral cortexes were isolated for morphological observations and the pyramidal cell layers were immunohistochemically stained for the detection of RAGE, NF-κB p65, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) as well. For RAGE and NF-κB p65, quantitative reverse transcriptase coupled to polymerase chain reaction (RT-PCR) was employed for determination of mRNA levels, and western blot was used to detect protein expression. Our results showed that long term hyperglycemia in diabetic rats caused the degeneration of neurons and the up-regulation of serum AGEs, and also the up-regulation of RAGE, NF-κB p65, VCAM-1 and ICAM-1 in the brain. We found that GSPE treatment improved the pathological changes of diabetic rats by modulating the AGEs/RAGE/NF-κB p65 pathway. This study enables us to further understand the key role that the AGEs/RAGE/NF-κB pathway plays in the pathogenesis of diabetic encephalopathy, and confirms that GSPE might be a therapeutical means to the prevention and treatment of this disorder.
关键词：diabetic encephalopathy;grape seed proanthocyanidin extracts;advanced glycation end products;nuclear factor-kappa B p65;cerebral cortex
