β-淀粉样蛋白脑室注射对大鼠海马星型胶质细胞活化和细胞增殖的作用

Intracerebroventricular injection of β-amyloid peptide improves astrocyte activation and proliferation in rat hippocampus

目的通过观察大鼠侧脑室注射β-淀粉蛋白(β-amyloid peptide,Aβ)后海马胶质纤维酸性蛋白(glialfibril-lary acidic protein,GFAP)的表达,探讨Aβ对海马局部星型胶质细胞活化增生的作用及对海马神经发生的可能影响。方法40只SD大鼠分为对照组(n=10)和实验组(n=30),将Aβ1-42注射入大鼠侧脑室,分别于术后3、7、14、30d处死动物,应用免疫组化方法观察GFAP的表达,并用免疫荧光双标标记BrdU、GFAP以判断增殖细胞的种类。结果实验组大鼠海马GFAP阳性细胞明显增加,到7d达到高峰,14d后逐渐下降,较对照组差异显著(P<0.01),实验组各时相点Br-dU、GFAP双标结果显示有部分BrdU阳性细胞GFAP为阳性,对照组双标阳性细胞很少。结论β-淀粉蛋白脑室注射后大鼠海马星型胶质细胞活化增生,部分增生的星型胶质细胞可能来源于神经干细胞。

Objective To evaluated the effect of unilateral intracerebroventricular injection （ i. c. v. ） of β-amyloid peptide （ Aβ） on astrocyte activation and neurogenesis by observing the expression of glial fibrillary acidic protein （ GFAP） in the hippocampus around the injecting area. Methods Total 40 adult male SD rats were randomly divided into control group （ n =10,2 for each time points） and experimental group （ n =30,6 for each time points） . Aβ1-42 （ 7 μg） or normal saline （ 7 μl） was injected into the lateral cerebroventricle of corresponding animals and then sacrificed at ,7,14 and 30 d after infusion. The expression of GFAP was observed by immunohistochemical staining. The double labeling of BrdU and GFAP was observed by immunofluorescence methods to identify the proliferative cells. Results The number of GFAP positive cells in the experimental group was increased significantly after the injection and reached maximum on the 7th day,and then decreased slowly after 14 d after the injection when compared with control （ P〈0. 01） . Some of BrdU positive cells were GFAP positive in the experimental group,while there were few double positive cells in the control group. Conclusion Astrocytes are activated after i. c. v. injection of Aβ,and some of them come from the neural stem cells （ NSCs） in the hippocampus. Aβ may be one of the factors promoting NSCs to develop into astrocytes.