Experimental Research On The Effects Of Glucocorticoids In Treating Mice With Olfactory Dysfunction From Influenza Virus Infection

Objective1. To observe the effects of intranasal glucocorticoid(GC) on the expression of olfactory marker protein (OMP), tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6) in murine olfactory mucosa and olfactory bulb(OB) infected by influenza virus.2. To observe the effects of systemic glucocorticoid on the expression of OMP, TNF-αand IL-6 in murine olfactory mucosa and olfactory bulb infected by influenza virus.3. To observe the different effects of intranasal glucocorticoid and systemic glucocorticoid on the expression of OMP, TNF-αand IL-6 in murine olfactory mucosa and olfactory bulb infected by influenza virus.4. To investigate the possible action mechanism of glucocorticoids for the treatment of olfactory dysfunction and the best route of administration.Methods1. An animal model was produced by intranasal application of influenza virus to mice.2. The expression of OMP, TNF-αand IL-6 in the olfactory mucosa and the olfactory bulb was tested by immunohistochemistry3. The expression of OMP in the olfactory mucosa and the olfactory bulb was tested by western blot.Results1. The up-regulation of OMP and the down-regulation of TNF-αand IL-6 in olfactory epithelium were observed in post-virus glucocorticoid groups compared with influenza virus control groups (P<0.05), but not significantly different compared with the non-infection control group (P>0.05);the down-regulation of OMP and the up-regulation of TNF-a and IL-6 were observed in influenza virus control groups than those in the non-infection control group(P<0.05).2. The up-regulation of OMP and the down-regulation of TNF-αand IL-6 in olfactory bulb were observed in post-virus glucocorticoid groups compared with influenza virus control groups (P<0.05),but not significantly different compared with the non-infection control group (P>0.05); the down-regulation of OMP and the up-regulation of TNF-a and IL-6 were observed in influenza virus control groups than those in the non-infection control group(P<0.05).3. Intranasal or systemic glucocorticoid can increase the expression of OMP, and inhibit the expression of TNF-αand IL-6 in murine olfactory mucosa and olfactory bulb infected by influenza virus. There was not significant difference in the effects of the both on the expression of OMP, TNF-αand IL-6 (P>0.05)Conclusion1. Intranasal glucocorticoid can enhance the expression of OMP and inhibit the expression of TNF-αand IL-6 in the olfactory mucosa and the olfactory bulb infected by influenza virus.2. Systemic glucocorticoid can increase the expression of OMP and inhibit the expression of TNF-αand IL-6 in the olfactory mucosa and the olfactory bulb infected by influenza virus.3. Glucocorticoids can enhance the expression of OMP and inhibit the expression of TNF-αand IL-6 in the olfactory mucosa and the olfactory bulb infected by influenza virus, which may be the mechanism of glucocorticoids for the treatment of olfactory dysfunction4. The effects of intranasal glucocorticoid on the expression of OMP, TNF-αand IL-6 in the olfactory mucosa and the olfactory bulb infected by influenza virus were no more in intranasal glucocorticoid groups than those in systemic glucocorticoid groups. Hence, intranasal glucocorticoid is the best route of administration in treating olfactory dysfunction.SummaryGlucocorticoids are the common used drugs in treating olfactory dysfunction,but the action mechanism is still poorly understood. An animal model was produced by intranasal application of influenza virus to mice in ordor to investigate the possible action mechanism that glucocorticoids treat the olfactory dysfunction. Animal model was firstly used to observe the effects of glucocorticoids on the murine olfactory mucosa and olfactory bulb infected by influenza virus. OMP, a protein related to olfaction, coexists in the olfactory mucosa and the olfactory bulb.There was the observation for the effects of glucocorticoids on the expression of OMP in the murine olfactory epithelium and olfactory bulb infected by influenza virus. Furthermore, influenza virus infection in the olfactory mucosa and the olfactory bulb can produce immnoreaction. It is generally believed that influenza virus infection can increase the expression of proinflammation such as TNF-αand IL-6, et al.Proinflammation is helpful to host against virus,but the overexpression of proinflammation will contribute to immnopathological injury. The study first investigated the effects of glucocorticoids on the expression of TNF-αand IL-6 in the murine olfactory epithelium and olfactory bulb infected by influenza virus.Meanwhile, the observation was done for OMP combined with TNF-αand IL-6 in ordor to investigate the possible action mechanism of glucocorticoids for olfactory dysfunction and the protection action for the murine olfactory epithelium and olfactory bulb infected by influenza virus.