摘要
目的:观察颅内给Aβ1-42和thiorphan后是否可以在恒河猴大脑内诱发类似AD患者的炎症反应,探讨该法建立猕猴AD模型的可行性。方法:开颅后先注射thiorphan到猕猴的大脑皮质和基底核消耗已存在的Neprilysin,然后再缓慢的注射孵育好的纤丝状Aβ1-42,后植入含有thiorphan的微渗透泵到基底核。HE染色及免疫组化观察大脑的炎症反应情况。结果:HE染色显示侧脑室室管膜的单层上皮结构消失,大量小胶质细胞浸润,形成多细胞层,小胶质细胞增生聚集成灶。免疫组化结果显示实验组恒河猴海马、基底核及皮质等部位出现星形胶质细胞增生。结论:Aβ1-42和thiorphan联合颅内给药后可以在恒河猴大脑内诱发广泛的炎症反应。
Objective： To observe the inflammatory reaction in Macaca Rhesus brain after co-infusing the Aβ 1-42 and Aβ-degyading enzyme neprilysin （NEP） inhibitor thiorphan, which used for the es- tablishment of Azheimer disease （AD） model. Methods： The skull was drilled and thiorphan was infused to the cerebral cortex and the basal ganglia to consume the exist neprilysin, then fibrilla Aβ1-42 was infused. For prolonged administration of inhibitor to basal ganglia, we implanted mini-osmotic pump（ Alzet 2ML4） in Macaca Rhesus brain. HE stain and immunostain were performed to observe the inflammatory reaction in monkey brains. Results： Proliferation of microglia were detected in lateral ventricle epithelium formation and basal ganglia by HE staining. Immuno stain showed that GFAP positive cells density were increased compared with control group. Conclusions： Infused Aβ1-42 and thiorphan in Macaca Rhesus brain induced inflammatory reaction as that was found out in AD patients.
出处
《药学与临床研究》
2009年第6期461-464,共4页
Pharmaceutical and Clinical Research
基金
广东省科技计划项目(2006B36004015
2009B060300017)
广东省自然科学基金项目(010086
06023013)
