糖调节受损大鼠认知障碍及脑组织NF-κBp65、TNF-α的表达

Cognition disorders and expression of NF-κBp65 and TNF-α in impaired glucose regulation rats

目的观察糖调节受损大鼠脑组织NF-κBp65、TNF-α及NF-κB mRNA、TNF-αmRNA表达,探讨糖耐量受损大鼠的炎症机制及其对认知功能障碍的影响。方法将Wistar大鼠随机分为对照组和实验组,高脂、高糖饲养法建立糖耐量受损大鼠模型;采用免疫组织化学和原位杂交的方法分别从蛋白水平和转录水平检测糖调节受损组与糖耐量正常组大鼠脑组织NF-κBp65、NF-κB mRNA和TNF-α、TNF-αmRNA的表达;Morris水迷宫法评定两组大鼠认知功能。结果与NGT组比较,IGR组第10周NF-κBp65、NF-κB mRNA高表达;第15周TNF-α、TNF-αmRNA高表达。两组间学习记忆能力在第5周无差异(P>0.05);在第10周IGR组优于NGT组;第15、第20周实验组逐次下降(P<0.05),低于同时点NGT组(P<0.05)。Pearson相关分析显示NF-κBp65、NF-κB mRNA和TNF-α、TNF-αmRNA高表达与大鼠认知障碍相关。结论糖调节受损与大鼠认知障碍相关,NF-κB调控的炎症反应可能是其重要机制。

Objective To explore the expression of NF-κBp65 and TNF-α in rat brain with cognition disorders,and discuss the relationship between impaired glucose regulation and cognition disorders from the perspective of inflammatory mechanism. Methods Impaired glucose tolerance model rats were made by high fat and sugar diet. The Morris water maze was applied in the study of learning and memory in rats. Expression of NF-κBp65 and TNF-α factor in rat brain were detected using immunohistochemistry and in situ hybridization. Results Compared with normal glucose tolerance group,the ability of learning and memory were significantly increased（ P〈0. 05） in the fifth week,while the ability in mpaired glucose regulation group were meaningfully decreased in each model subgroup at 15th、20th week（ P〈0. 05）,and lower than the normal glucose tolerance group. Compared with the normal glucose tolerance group the NF-κBp65 and NF-κB mRNA were highly expressed from 10 th week,while the TNF-α and TNF-α mRNA were highly expressed from 15 th week. There were significant difference between the two groups. Conclusion There is a relationship between impaired glucose regulation and cognition disorders,its mechanism may have some connection with the high expression of NF-κB、TNF-α.