Tian Zhiyan, Wang Jinhua, Xu Ming, Wang Yan, Zhang Miao, Zhou Yuying
Department of Neurology, Tianjin Huanhu Hospital, Jinnan District, Tianjin, PR China.
Cell Physiol Biochem. 2016;40(6):1670-1677. doi: 10.1159/000453216. Epub 2016 Dec 23.
To investigate the effects of resveratrol on cognitive impairment in streptozotocin (STZ)-induced diabetic rats and to explore the mechanisms of that phenomenon.
Sixty healthy male Sprague Dawley rats were randomly divided into four groups: normal control group (Con group, n = 15), Res group (normal Sprague Dawley rats treated with resveratrol, n = 15), diabetes mellitus group (DM group, n = 15) and DM + Res group (diabetic rats treat with resveratrol, n = 15). Streptozotocin (STZ) was injected intraperitoneally to establish the diabetic model. One week after diabetic model induction, the animals in the Res group and the DM + Res group received resveratrol intraperitoneally once a day for consecutive 4 weeks. The Morris water maze test was applied to assess the effect of resveratrol on learning and memory. To explore the mechanisms of resveratrol on cognition, we detected the protein expression levels of Caspase-3, Bcl-2, Bax, NMDAR1 (N-Methyl-d-Aspartate receptor) and BDNF (Brain Derived Neurotrophic Factor) via western blotting analysis.
Resveratrol has no obvious effect on normal SD rats. Compared to Con group, cognitive ability was significantly impaired with increased expression of Caspase-3, Bax and down-regulation of Bcl-2, NMDAR1 and BDNF in diabetic rats. By contrast, resveratrol treatment improved the cognitive decline. Evidently, resveratrol treatment reversed diabetes-induced changes of protein expression.
Resveratrol significantly ameliorates cognitive decline in STZ-induced diabetic model rats. The potential mechanism underlying the protective effect could be attributed to the inhibition of hippocampal apoptosis through the Bcl-2, Bax and Caspase-3 signaling pathways and improvement of synaptic dysfunction. BDNF may also play an indispensable role in this mechanism.
研究白藜芦醇对链脲佐菌素（STZ）诱导的糖尿病大鼠认知功能障碍的影响，并探讨其作用机制。
将60只健康雄性Sprague Dawley大鼠随机分为四组：正常对照组（Con组，n = 15）、Res组（正常Sprague Dawley大鼠给予白藜芦醇处理，n = 15）、糖尿病组（DM组，n = 15）和DM + Res组（糖尿病大鼠给予白藜芦醇处理，n = 15）。腹腔注射链脲佐菌素（STZ）建立糖尿病模型。糖尿病模型诱导1周后，Res组和DM + Res组动物连续4周每天腹腔注射一次白藜芦醇。采用Morris水迷宫试验评估白藜芦醇对学习记忆的影响。为探讨白藜芦醇对认知的作用机制，通过蛋白质印迹分析检测Caspase-3、Bcl-2、Bax、NMDAR1（N-甲基-D-天冬氨酸受体）和BDNF（脑源性神经营养因子）的蛋白表达水平。
白藜芦醇对正常SD大鼠无明显影响。与Con组相比，糖尿病大鼠的认知能力显著受损，Caspase-3、Bax表达增加，Bcl-2、NMDAR1和BDNF表达下调。相比之下，白藜芦醇治疗改善了认知功能下降。显然，白藜芦醇治疗逆转了糖尿病诱导的蛋白表达变化。
白藜芦醇显著改善STZ诱导的糖尿病模型大鼠的认知功能下降。其保护作用的潜在机制可能归因于通过Bcl-2、Bax和Caspase-3信号通路抑制海马细胞凋亡以及改善突触功能障碍。BDNF在该机制中可能也发挥着不可或缺的作用。
