糖尿病小鼠加重脑缺血后认知障碍的相关机制研究

目的探讨氧化应激损伤对糖尿病小鼠局灶性脑缺血后认知功能的影响。方法制备糖尿病模型,参照Longa等方法制成大鼠局灶性大脑中动脉阻断(MCAO)模型,采用Longa法进行神经功能缺失评分,苏木精-伊红染色测定梗死体积,Western blotting法检测Nrf2/HO-1及认知相关性蛋白p-Ca MKII/Ca MKII、p-Synapain/Synapain、p-Glu R1/Glu R1的蛋白表达。结果糖尿病小鼠局灶性脑缺血-再灌注后神经功能缺失评分、梗死体积较非糖尿病组明显严重(P0.05),同时伴有脑组织Nrf2/HO-1、p-Ca MKII/Ca MKII、p-Synapain/Synapain、p-Glu R1/Glu R1蛋白表达下调(P0.05)。结论糖尿病小鼠局灶性脑缺血—再灌注后Nrf2/HO-1表达降低,且与神经功能缺失及p-Ca MKII/Ca MKII、p-Synapain/Synapain、p-Glu R1/Glu R1表达下调一致,提示Nrf2/HO-1是糖尿病脑梗死后导致认知障碍的关键环节。

The effect of Nrf2/ARE in cerebral ischemia with diabetic after strke in mice

Objective To explore the effect of Nef2/HO-1 in brain tissue of focal cerebral ischemic mice with diabetic and non-diabeticmiceMethod 50 male C57BL/6J mice were divided randomly into control and DM groups, and these group was further divided into two sub-groups(MCAO and DM+MCAO groups)). The model with thread embolism of middle cerebral artery occlusion(MCAO)in mice was made and the protein expression of Nrf2/HO-1,p-CaMKII/CaMKII,p-Synapain/Synapain,p-GluR1/GluR1 in the brain tissue of infaction was determined simultaneously by Western blotting.Results Diabetic mice demonstrated more severe neurologic deficits, infarct size and inflammatory damage after MCAO, The protein expression of Nrf2/HO-1,p-CaMKII/CaMKII,p-Synapain/Synapain,p-GluR1/GluR1 reduced (P<0.05) in the brain tissue surrounding cerebral ischemic (P<0.05) simultaneously.Conclusion The expression of Nrf2/HO-1,p-CaMKII/CaMKII,p-Synapain/Synapain,p-GluR1/GluR1 discreased in brain tissue surrounding cerebral ischemic in diabetic mice. It is indicated that Nrf2/HO-1 might be involved in cognitive dysfunction of cerebral ischemic in diabetic mice.