海马内注射LPS后诱导大鼠脑内BACE-1的表达变化

Expression change of β-site amyloid precursor protein cleavage enzyme-1 in the cerebral after LPS injection into hippocampus of rats

目的:探讨脑内注射内毒素脂多糖(lipoolysaccharide,LPS)诱导的大鼠慢性神经炎症脑内β-位点淀粉蛋白剪切酶-1(β-site amyloid precursor protein cleavage enzyme-1,BACE-1)的表达变化。方法:依赖立体定位技术,在成年SD雄性大鼠右侧海马内注入LPS,动物存活15 d。运用免疫组织化学方法检测大鼠脑内BACE-1,β-淀粉样前体蛋白(β-amyloid precursor protein,APP)以及β-淀粉样蛋白(β-amyloid,Aβ)等阿尔茨海默病(Alzheimer’s disease,AD)相关蛋白的表达变化;采用免疫荧光双重标记技术,观察BACE-1在大鼠脑内的表达情况和定位分布。结果:在正常哺乳动物的大脑内,BACE-1主要表达在海马苔藓纤维和嗅球的嗅小球层,脑皮质内则表现为弱而弥散的神经毡反应性。本研究结果显示:LPS注射对侧大脑半球中BACE-1表现出上述正常的表达模式。然而,与注射对侧相比,LPS处理的大鼠注射侧大脑的皮质和海马区域均有BACE-1的位点特异性的表达上调,尤其在注射的针道周围明显,同时伴有APP和Aβ的表达增加。免疫荧光双标结果显示:上调的BACE-1定位于失营养性轴突末梢。结论:LPS诱导的大鼠神经炎症脑内,BACE-1表达上调,且上调的BACE-1主要定位于轴突末梢,高表达的BACE-1可能对AD的发生具有促进作用。

Objective: To investigate the expression changes of β-site amyloid precursor protein cleavage enzyme-1(BACE-1)after chronic brain inflammatory induced by lipopolysaccharide(LPS). Methods: Depending on three-dimensional positioning technology,we injected LPS to the right lateral hippocampus of adult male SD rats. Animals were survived for 15 days. Immunohistochemistry was used to detect the expression of BACE-1 and Alzheimer's disease immune related molecules such as the APP and Aβ in the cerebral cortex and hippocampus. The expression positioning of BACEI positive cells were observed by immunofluorescence double labeling. Results: In normal mammalian brains BACE-1 immunoreactivity is largely expressed in the neuropil in a diffuse pattern except for a distinct heavy labeling at selected neuronal terminal fields including the mossy fiber terminals of hippocampus and olfactory glomeruli. In the present study,BACE-1 labeling in the contralateral cerebrum in the LPS-injected animals exhibited the aforementioned normal distribution pattern. On the contrary,BACE-1 labeled neuritic structures emerged in the ipsilateral hemisphere of the LPS-treated brains in a site-specific manner. Thus,increased BACE-1 labeling appeared in both the cortex and hippocampal especially evident around the needle track. Then,the expression of APP and Aβ were also significantly increased in the injectionside. Double immunofluorescence labeling showed increased expression of BACE-1 located in the distal axon loss nutrition(BACE-1 and SYN immune coexistence). Conclusion: LPS can elicit up-regulation of BACE-1,which locatated in the distal axon loss nutrition,high expression of BACE-1 may play a potential role in the occurrence of AD.