中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (2): 272-279.doi: 10.4103/1673-5374.220779

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

高同型半胱氨酸血症下调Hes1和Hes5表达可造成嗅球神经元损伤

  

  • 收稿日期:2017-12-02 出版日期:2018-02-15 发布日期:2018-02-15
  • 基金资助:

    中国国家自然科学基金项目（81560084，81560208），宁夏医科大学优势学科群项目基金（XY201414）

Hyperhomocysteinemia induces injury in olfactory bulb neurons by downregulating Hes1 and Hes5 expression

Jing-wen Zhang1, 2, Bo Pang1, Qi Zhao1, Yue Chang1, Yi-li Wang2, Yi-deng Jiang1, Li Jing1   

  1. 1 School of Basic Medical Science, Ningxia Key Laboratory of Cerebrocranial Diseases-Incubation Base of National Key Laboratory, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region, China
    2 Institute of Immunopathology, Medical School, Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
  • Received:2017-12-02 Online:2018-02-15 Published:2018-02-15
  • Contact: Yi-li Wang or Li Jing,wangyili@mail.xjtu.edu.cn or jingli@nxmu.edu.cn.
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 81560084, 81560208; a grant from the Project of Superior Discipline Groups in Ningxia Medical University of China, No. XY201414.

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摘要：

有研究显示高同型半胱氨酸血症与神经退行性疾病有关，但由同型半胱氨酸诱导的嗅球神经元损伤的病理组织学改变及其机制尚不清楚。因而实验以1.7％同型半胱氨酸饮食诱导ApoE-/-小鼠建立高同型半胱氨酸血症模型。以苏木精-伊红染色和Pischingert染色观察嗅球病理变化，以TUNEL染色检测嗅球中细胞凋亡，以透射电镜观察神经元超微结构异常，以免疫组化染色、免疫荧光染色以及Western blot分析检测Hes1和Hes5免疫阳性反应及相关表达水平。结果显示，高同型半胱氨酸血症小鼠嗅球结构无明显异常，但嗅球中TUNEL阳性颗粒细胞数量增多，线粒体内脂褐素和空泡化明显，Hes1和Hes5表达降低，提示高同型半胱氨酸血症是通过下调Hes1和Hes5表达造成嗅球神经元的损伤。

orcid:0000-0003-2233-5453(Li Jing)

关键词: 神经再生, 嗅球, 细胞凋亡, 神经元, 尼氏小体, 同型半胱氨酸, Hes1, Hes5

Abstract:

Hyperhomocysteinemia has been shown to be associated with neurodegenerative diseases; however, lesions or histological changes and mechanisms underlying homocysteine-induced injury in olfactory bulb neurons remain unclear. In this study, hyperhomocysteinemia was induced in apolipoprotein E-deficient mice with 1.7% methionine. Pathological changes in the olfactory bulb were observed through hematoxylin-eosin and Pischingert staining. Cell apoptosis in the olfactory bulb was determined through terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. Transmission electron microscopy revealed an abnormal ultrastructure of neurons. Furthermore, immunoreactivity and expression of the hairy enhancer of the split 1 (Hes1) and Hes5 were measured using immunohistochemistry, immunofluorescence, and western blot assay. Our results revealed no significant structural abnormality in the olfactory bulb of hyperhomocysteinemic mice. However, the number of TUNEL-positive cells increased in the olfactory bulb, lipofuscin and vacuolization were visible in mitochondria, and the expression of Hes1 and Hes5 decreased. These findings confirm that hyperhomocysteinemia induces injury in olfactory bulb neurons by downregulating Hes1 and Hes5 expression.

Key words: nerve regeneration, olfactory bulb, apoptosis, neurons, Nissl body, homocysteine, hairy enhancer of split 1, hairy enhancer of split 5, neural regeneration