The alterations of inducible nitric oxide synthase in the mouse brainstem during herpes simplex virus type 1-induced facial palsy
The alterations of inducible nitric oxide synthase in the mouse brainstem during herpes simplex virus type 1-induced facial palsy
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DOI：
10.1179/1743132812y.0000000017
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发表时间：
2012-03
影响因子：
1.9
通讯作者：
Y. Mao;Z. Fan;Yue-chen Han;Wenwen Liu;Lei Xu;Zhen Jiang;Jian-feng Li;Haibo Wang
中科院分区：
文献类型：
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作者：
Y. Mao;Z. Fan;Yue-chen Han;Wenwen Liu;Lei Xu;Zhen Jiang;Jian-feng Li;Haibo Wang
摘要目的：本研究旨在观察单纯疱疹病毒1型（HSV-1）诱导的面神经麻痹小鼠脑干中诱导型一氧化氮合酶（iNOS）的变化及糖皮质激素的抑制作用。方法：将HSV-1接种于小鼠后耳廓表面，建立动物模型。将瘫痪的小鼠分成三组，如文中所详述。一组在不同时间点处死小鼠，另两组每天注射甲基强的松龙琥珀酸钠（MPSS）或MPSS与糖皮质激素受体阻断剂（RU 486）联合给药，持续2天。通过苏木精和伊红（H&E）染色和改进的三色染色评价形态学变化。采用逆转录-聚合酶链反应（RT-PCR）、免疫印迹和免疫组织化学方法检测iNOS在脑干面神经核的表达和定位。结果：接种HSV-1后，49.09%的小鼠出现单侧面瘫。用形态学方法观察了单纯疱疹病毒1型（HSV-1）感染对瘫痪小鼠面神经和面神经核的损伤。此外，我们还发现iNOS在正常的胶质细胞和运动神经元中呈低水平表达，在面瘫后表达显著上调，MPSS可抑制iNOS的表达。糖皮质激素受体抑制剂RU 486可阻断MPSS的抑制作用。讨论内容：本研究表明，在早期阶段的iNOS活性增强是HSV-1诱导的面瘫的重要机制。MPSS能有效减轻HSV-1介导的神经系统损伤，这与其抑制iNOS的表达密切相关。
Abstract Objective: We sought to study the alterations of inducible nitric oxide synthase (iNOS) in the mouse brainstem during facial paralysis induced by herpes simplex virus type 1 (HSV-1) and the inhibitory effects of glucocorticoids. Methods: HSV-1 was inoculated into the surface of posterior auricle of mouse to set up an animal model. The paralyzed mice were divided in three groups as detailed in text. Mice, in one group, were killed at different time points and, in other two groups, were injected daily for 2 days with methylprednisolone sodium succinate (MPSS) or with combined administration of MPSS and glucocorticoid receptor blocker (RU486). Morphological changes were evaluated by means of hematoxylin and eosin (H&E) staining and improved trichrome staining. The expression and location of iNOS in the facial nucleus of brainstem was detected by reverse transcription-polymerase chain reaction (RT-PCR), western blot, and immunohistochemistry. Results: After inoculated by HSV-1, 49·09% of mice developed unilateral facial paralysis. Injuries in response to HSV-1 infection in the facial nerves and facial nucleus of paralyzed mice were observed by morphological methods. Besides, we found that iNOS was present in normal glial cells and motor neurons at low levels and was upregulated dramatically after facial paralysis, which could be inhibited by MPSS. RU486, a glucocorticoid receptor inhibitor, could block the inhibitory effects of MPSS. Discussion: The present study demonstrates that the enhanced activity of iNOS in the early phase represents an important mechanism in HSV-1-induced facial paralysis. MPSS can effectively attenuate HSV-1-mediated damages in nerve system, which is closely associated to its inhibitory effect on expression of iNOS.