The Alterations Of SHARPIN In Mouse Brainstem During Herpes Simplex Virus Type 1-induced Facial Palsy And The Inhibitory Effect Of Glucocorticoid On SHARPIN Expression

Objectives:To establish an animal model of facial nerve palsy in mice induced by herpes simplex virus type 1 (HSV-1) infection to clarify the expression change of SHARPIN in the mouse during the development of facial palsy caused by HSV-1 and the inhibitory effect of corticosteroids so as to explore the possible mechanism underlying the action of SHARPIN in this model.Methods:142 mice were stochastically classified into three groups:virus inoculated group, normal saline group, and normal control group. Subsequently, the paralyzed mice in virus inoculated group were further divided into three subgroups (groups A-C). In the normal saline group,25 mice were alternately inoculated with normal saline. In the normal control,9 healthy mice were chosen to serve as control without treatment. The expression and location of SHARPIN in the facial nucleus of brainstem were detected respectively by quantitative real-time polymerase chain reaction, western blot and immunofluorescence.Results:69 (63.89%) mice developed unilateral facial paralysis between 2 and 5 days after HSV-1 inoculation. mRNA expression of brainstem sharpin was at a low level in the normal control group, while was dramatically increased in the HSV-1-infected paralyzed group (P< 0.05). The mRNA expression of sharpin was peaked at 2 days post-induction of facial paralysis (P< 0.01) and then followed by a decline.7 days later, the mRNA expression of sharpin in the paralyzed brainstem was reduced to normal level. The alterations of SHARPIN protein levels in the brainstem were coincident with that of sharpin mRNA levels. SHARPIN expression was at a low level in normal control group while at a special high level in paralyzed group at 2 days. In group HSV-1+MPSS, the SHARPIN expression at 2 days was significantly downregulated by MPSS compared with group HSV-1 (P< 0.01), while still higher than group normal control (P< 0.05). The inhibitory effect of MPSS on SHARPIN expression was eliminated after combined administration of MPSS and RU486 in group HSV-1+MPSS+RU486, as the expression of SHARPIN was still higher than that of group HSV-1 (P< 0.05).Conclusions:Our results suggest that SHARPIN is related to the pathogenesis of facial palsy. MPSS can effectively inhibit the expression of SHARPIN that may contribute to attenuate HSV-1-mediated nervous system damage.