The Alterations Of Matrix Metalloproteinase-9in Mouse Brainstem During Herpes Simplex Virus Type1-induced Facial Palsy And The Inhibitory Effect Of Methylprednisolone Sodium Succinate On Matrix Metalloproteinase-9Expression

Partâ… The Alterations of Matrix Metalloproteinase-9in Mouse Brainstem During Herpes Simplex Virus Type1-induced Facial PalsyObjectives:To establish an animal model of facial nerve palsy in mice induced by herpes simplex virus type1(HSV-1) infection so as to explore the changes of matrix metalloproteinase-9(MMP9) in the mouse brainstem during the development of facial paralysis induced by HSV-1.Methods:160four-weeks Balb/c male mice were randomly divided into virus inoculated group (121mice), saline group (30mice) and normal control group (9mice). HSV-1was inoculated into the surface of posterior auricle of mouse to establish a paralyzed animal model. Western blot and Immunofluorescent staining were used to detect the level of MMP9protein, real-time PCR was used to measure the level of MMP9mRNA.Results:Of the121mice subjected to retroauricular inoculation with HSV-1,63(52.07%) developed unilateral facial paralysis between2and5days. In the condition without any administration, the facial paralysis recovered spontaneously within a period of3-7days. Of the63mice,33mice were involved in experiment Part1as facial paralysis group. In the saline group, the expressions of MMP9mRNA in the facial nucleus of brainstem were at low levels, and compared with the control group there were no significant difference (P>0.05). In facial paralysis group, the expression of MMP9mRNA increased at6h post-induction of facial paralysis, and peaked at2d, showing a significant difference compared with control group (P<0.01), and then followed by a decline in the tendency to normal level. MMP9protein expression in the saline group was the same as mRNA expression. In facial paralysis group, the expression of MMP9protein increased at6h, and peaked at2d, showing a significant difference compared with control group (P<0.01). Confocal laser scanning microscopy showed that MMP9was present at a low level in normal control group, while strongly expressed in paralyzed group at the time point of2days post-induction of facial paralysis.Conclusions:Our findings suggest that MMP9in mouse brainstem is involved in the evolution of facial palsy induced by HSV-1and may play an important role in the pathogenesis of this disease. Part â…¡Inhibitory Effect of Methylprednisolone Sodium Succinate on Matrix Metalloproteinase-9Expression in Brainstem of Paralyzed MiceObjectives:To explore the inhibitory effect of methylprednisolone sodium succinate (MPSS) on MMP9expression in the mouse brainstem during the development of facial paralysis induced by HSV-1.Methods:30mice with facial paralysis induced by HSV-1were randomly divided into two groups. In group one, mice were injected daily with MPSS for2days; in group two, mice were injected daily with combination of MPSS and glucocorticoid receptor blocker (RU486) for2days. In the two groups, western blot was used to detect the level of MMP9protein at the time point of2days post-induction of facial paralysis. MMP9protein was also be detected in paralyzed group without any administration at the time point of2days and in normal control group as same as in experiment Part1.Results:Expression of MMP9of paralyzed mice was inhibited by MPSS, and the inhibition could be blocked by RU486. At the time point of2days, expressions of MMP9protein in paralyzed mice with administration of MPSS were lower significantly than those in paralyzed mice without any administration and those with combination of MPSS and RU486(P<0.01), and were higher significantly than normal control (P<0.01).Conclusions:MPSS might effectively relieve HSV-1-mediated damages by inhibitory effect on expression of MMP9in HSV-1-induced facial paralysis.