Study On The Curative Effect Of Nerve Growth Factor In The Treatment Of Olfactory Dysfunction Mice By Nasal Atomization

Objective: To investigate the therapeutic effect of different doses of nerve growth factor(NGF)administered nasally on olfactory dysfunctional(OD)mice.Methods: Experiments were performed using 7-week-old SPF-grade healthy male BALB/c mice.In the experiment,3-methylindole was injected intraperitoneally to establish a mouse model of olfactory impairment.According to the results of the buried food pellet tests,27 mice were successfully modeled.Randomly divide model mice into 4 experimental groups(groups A,B,C,and D,6 mice in each group),and a blank control group(group E,3 mice in total).The experimental group was nebulized with different doses of NGF every day(group A 25μg/Kg,group B 50 μg/Kg,group C 100 μg/Kg,group D 250 μg/Kg),and the control group E daily only nebulize the same amount of normal saline(4ml)for 21 consecutive days.Buried food pellet tests were carried out on the 7th,14 th,and 21 st days of nebulization,and mouse’s olfactory function was preliminarily judged according to the length of buried food tests time.All mice were killed at 21 days after nebulization,and the olfactory epithelium(OE)of nasal mucosa was collected for immunohistochemical staining(IHC).The average optical density(AOD)of the expression of olfactory marker protein(OMP)in OE was calculated and analyzed,and each recovery of olfactory receptor neurons(ORNs)in the group mice.Results: After 7 days of atomization,the results of the buried food pellet tests indicated that the time of each experimental group was within 220-270 s,and there was no statistical difference(P > 0.05);after 14 days of atomization,the foraging time of all experimental groups was shorter than before,and there was a significant difference between all groups(P < 0.01),and it showed a trend that the larger the treatment dose,the shorter the foraging time;after 21 days of nebulization,the buried food tests time of all experimental groups was further shortened,and the time of group A was significantly longer than that of other groups.In the experimental group(P < 0.01),the results of groups B,C,and D have recovered to about 60 seconds,and there is no significant difference between these three groups(P > 0.05).In the control group,the time was >250s throughout the whole experiment,and no sign of any smell recovery occurred.The results of immunohistochemistry indicated that after 21 days of administration,there were significant differences in the AOD of the mice in each experimental group.The AOD value of group A was significantly lower than that of other experimental groups(P < 0.01),and there was no statistical difference in the comparison between groups B,C,and D.difference(P >0.01).Conclusions: In the olfactory recovery treatment for OD caused by 3-MI,nasal atomization of50 μg/Kg NGF for 21 consecutive days can restore the olfactory function,and increasing the treatment dose cannot improve the therapeutic effect.