C1型尼曼-匹克症小鼠嗅球细胞的病理变化  

Pathological changes of the olfactory bulbs in the Niemann-Pick type C1 mice

作　　者：闫欣[1,2] 乔梁[1,2] 杨恩慧[1,2] 林俊堂[1,2] 

机构地区：[1]新乡医学院生命科学技术学院,河南新乡453003 [2]河南省医用组织再生重点实验室,河南新乡453003

出　　处：《解剖学报》2016年第1期2-6,共5页Acta Anatomica Sinica

基　　金：国家自然科学基金(81400936);国家自然科学基金-河南人才培养联合基金(U1304808)

摘　　要：目的通过观察NPC1基因突变型小鼠嗅球的形态学变化,探讨C1型尼曼-匹克症对嗅觉系统的影响。方法提取小鼠尾部组织DNA进行聚合酶链反应检测种系基因型;选取出生后第30天的野生型和突变型小鼠,采用免疫组织化学方法观察对比嗅球系统中神经元轴突的形态结构和髓鞘形成,以及神经丝蛋白(SMI31)和髓鞘碱性蛋白(MBP)的表达情况;TUNEL方法检测嗅球神经细胞的凋亡情况。结果 NPC1基因突变型小鼠嗅球中NPC1蛋白表达明显降低,神经细胞凋亡增加;SMI31免疫荧光显示嗅球内SMI31发生变性聚集,导致神经纤维缠结;同时,MBP蛋白表达量明显降低,髓鞘形成受到抑制。结论 NPC1基因突变能够引起嗅球神经细胞发生病理性变化,影响嗅觉系统的正常功能。Objective To examine the impact of Niemann-Pick disease type C1 on the olfactory system, we investigated the morphological changes of the olfactory bulbs in NPCI mutant mouse. Methods The genomic DNA was extracted from mouse tails for genotyping by PCR;30-day-old mice including wild type and NPC1 gene mutation were selected, and immunohistochemistry was performed to examine and compare the axonal structure, the myelination process, as well as the expression of SMI31 and myelin basic protein （MBP） in the olfactory bulbs;The cell apoptosis was analyzed by TUNEL assay. Results In NPC1 ^-/- mice, the expression of NPC1 protein was rarely detected, but TUNEL-positive cells were increased. Immunofluorescence using SMI31 antibody indicated accumulation.of neurofilament and formation of axonal spheroids in the NPC1^-/- olfactory bulbs. Furthermore, the decreased expression of MBP protein was found in NPC1^ -/- olfactory system, which was associated with perturbed myelination. Conclusion Our data show that pathological changes in the olfactory bulbs of NPC1 mutant mice are accompanied by olfactory defects.

关 键 词：C1型尼曼-匹克症 嗅觉障碍 神经元 髓鞘障碍 免疫组织化学 小鼠 

分 类 号：Q954.48[生物学—动物学]