脑缺血对阿尔茨海默病模型大鼠认知功能的影响及其机制探讨被引量：9

Effect and Mechanism of Cerebral Ischemia on the Cognitive Function in a Rat Model of Alzheimer Disease

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摘要目的探讨脑缺血对阿尔茨海默病(AD)病程进展的影响及其机制。方法采用大鼠海马注射凝聚态β淀粉样蛋白(Aβ)1-40建立AD模型,再于海马内注射ET-1建立脑缺血条件,观察脑缺血后AD样大鼠认知功能以及海马内Aβ沉积、神经元丢失和异常磷酸化tau表达的变化;采用免疫组化、原位杂交和RT-PCR法检测海马内星形胶质细胞数量和IL-1、TNF-α表达的变化。结果脑缺血后AD样大鼠的认知功能明显下降,海马内Aβ沉积增加,神经元丢失增加,异常磷酸化tau表达增加,星形胶质细胞的数量以及IL-1和TNF-α的表达显著增加(均P<0.01)。结论脑缺血加重了AD样大鼠的认知功能障碍和海马病理损伤,显著增加的星形胶质细胞及IL-1和TNF-α的表达参与了这一过程。防治脑缺血和抗炎治疗可能成为减缓AD进展的新途径。 Objective To investigate the effect and mechanism of cerebral ischemia on cognitive function of rats in a model of Alzheimer disease （AD）. Methods AD rat model was established by hippocampal injection of Aβ- 40. Then AD-like rats were injected Endothelin-1 （ET-1） into the injected hippocamus to establish cerebral ischemic status. The changes of cognitive function, Aβ deposition, neuronal loss and expression of abnormally phosphorylated tau protein in the hippocampus of AD-like rats affected by cerebral ischemia were observed. Immunohistochemistry, in situ hybridization and reverse transcription-polymerase chain reaction methods were adopted to detect the changes of astrocytes numbers and expression of inflammatory cytokines including IL-1 and TNF-α. Results Cognitive function of AD-like rats decreased obviously and Aβ deposition, loss of neurons, expression of abnormally phosphorylated tau protein, astrocytes and expression of IL-1, TNF-α in the hippocampus increased after cerebral ischemia （P 〈 0.01 ）. Conclusions Cerebral ischemia aggravated the cognitive and pathological impairment in the hippocampus of AD-like rats. Significant increases of astrocytes and IL-1, TNF-α participated in the process. Prevention and therapy of cerebral ischemia and anti-inflammatory therapy might be a new way to relieve the progression of AD.

作者李静周华东王延江张猛许志强方传勤

机构地区第三军医大学大坪医院野战外科研究所神经内科

出处《中国神经免疫学和神经病学杂志》 CAS 2008年第5期360-364,398,399,共7页 Chinese Journal of Neuroimmunology and Neurology

关键词阿尔茨海默病脑缺血认知功能白细胞介素-1 肿瘤坏死因子-Α Alzheimer disease cerebral isehemia cognitive function IL-1 TNF-α

分类号 R743 [医药卫生—神经病学与精神病学]

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