脑缺血对阿尔茨海默病大鼠认知功能的影响及炎性机制探讨

Study on the Effect and Inflammatory Mechanism of Cerebral Ischemia on Cognitive Function of Alzheime's Disease Rats

目的:探讨脑缺血对阿尔茨海默病(AD)大鼠认知功能的影响及可能机制。方法:大鼠海马注射Aβ1-40成功建立AD大鼠模型后,于AD大鼠右侧纹状体注射内皮素-1建立脑缺血模型,Morris水迷宫检测脑缺血后AD大鼠认知功能的变化,免疫组化、原位杂交和RT-PCR检测海马内星形胶质细胞和IL-1、TNF-α的变化。结果:脑缺血后AD大鼠认知功能明显下降(P<0.01),海马内星形胶质细胞和炎性细胞因子IL-1、TNF-α的表达都较单纯AD显著增加(P<0.01)。结论:脑缺血加重了AD大鼠的认知功能障碍,炎性机制参与了脑缺血促进AD进展的过程。

Aim： To investigate the effect and inflammatory mechanism of cerebral ischemia on cognitive function of Alzheimer＇ s disease（AD） rats. Methods ： AD rat model was established by hippocampal injection of A β1-40. Then AD rats were injected by Endothelin-1 （ET-1） into the right striatum to establish cerebral ischemic model. Morris water maze was used to evaluate the change of cognitive function of AD rats with cerebral ischemia.The mechanism of cerebral ischemia affecting AD rats was approached from the change of astrocytes and inflammatory cytokines including IL-1 and TNF-α by immunohistochemistry, in situ hybridization and reverse transcription-polymerase chain reaction. Results. Compared with the simple AD rats, the AD rats exposed to cerebral ischemia showed deterioration of conitive function（P 〈 0.01）.The number of astrocytes and the expression of inflammatory cytokine IL-1, TNF-α in the hippocampus increased significantly in the group of AD with cerebral ischemia（P 〈 0.01）. Conclusion ： Cerebral ischemia aggravated the cognitive impairment of AD rats. Inflammatory mechaniasm participated in the process that cerebral ischemia enhanced the progression of AD.