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单纯疱疹病毒 1 型诱导的面瘫小鼠脑干基质金属蛋白酶-9 的改变。

The alterations of matrix metalloproteinase-9 in mouse brainstem during herpes simplex virus type 1-induced facial palsy.

机构信息

Department of Otorhinolaryngology Head and Neck Surgery, Provincial Hospital affiliated to Shandong University, No.4, West Duanxing Road, Jinan, 250022, China.

出版信息

J Mol Neurosci. 2013 Nov;51(3):703-9. doi: 10.1007/s12031-013-0051-3. Epub 2013 Jul 2.

Abstract

The aim of this study is to explore the changes of matrix metalloproteinase-9 (MMP9) in the mouse brainstem during the development of facial paralysis induced by herpes simplex virus type 1 (HSV-1) and the inhibitory effect of methylprednisolone sodium succinate (MPSS) on MMP9 expression. HSV-1 was inoculated into the surface of posterior auricle of mouse to establish a paralyzed animal model. The paralyzed mice were divided randomly into three groups. In one group without any treatment, mice were killed at different time points of 6 h, 1, 2, 3, and 7 days post-induction of facial paralysis; in the other two groups, mice were injected daily with MPSS and a combination of MPSS and glucocorticoid receptor blocker (RU486) for 2 days, respectively. The expression of MMP9 in the facial nucleus of brainstem was detected by Western blot, quantitative real-time polymerase chain reaction, and immunofluorescence technique. A total of 52.07 % of mice developed unilateral facial paralysis after inoculated with HSV-1. Both mRNA and protein expression of MMP9 were present at low levels in normal facial nucleus of brainstem and were increased significantly after facial paralysis with its peak time at 2 days post-induction of facial paralysis. Expression of MMP9 of paralyzed mice was inhibited by MPSS, and the inhibition could be blocked by RU486. Our findings suggest that MMP9 in mouse brainstem is involved in the evolution of facial palsy induced by HSV-1 and may play an important role in the pathogenesis of this disease. MPSS might effectively relieve HSV-1-mediated damages by inhibitory effect on expression of MMP9 in HSV-1-induced facial paralysis.

摘要

本研究旨在探讨单纯疱疹病毒 1 型(HSV-1)诱导的面瘫小鼠脑干基质金属蛋白酶 9(MMP9)的变化及甲泼尼龙琥珀酸钠(MPSS)对 MMP9 表达的抑制作用。将 HSV-1 接种于小鼠耳后表面,建立面瘫动物模型。将面瘫小鼠随机分为三组,一组不做任何处理,于面瘫诱导后 6h、1、2、3、7 天不同时间点处死小鼠;另外两组分别每天给予 MPSS 和 MPSS 联合糖皮质激素受体阻滞剂(RU486)治疗 2 天。采用 Western blot、实时定量聚合酶链反应和免疫荧光技术检测脑干面神经核中 MMP9 的表达。52.07%的小鼠接种 HSV-1 后出现单侧面瘫。正常面神经核中 MMP9 的 mRNA 和蛋白表达水平较低,面瘫后明显升高,面瘫诱导后 2 天达高峰。MPSS 可抑制 MMP9 的表达,RU486 可阻断这种抑制作用。我们的研究结果表明,HSV-1 诱导的面瘫小鼠脑干 MMP9 参与了面瘫的演变,可能在疾病发病机制中起重要作用。MPSS 可能通过抑制 HSV-1 诱导的面瘫中 MMP9 的表达,有效缓解 HSV-1 介导的损伤。

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