Expression Pattern And Regulation Of Glucocorticoid On Aquaporin 5 In Rat Model With Chronic Rhinosinusitis

Objective1.To develop a rat model with rhinogenic chronic rhinosinusitis(CRS)and observe biological characteristics during succession of inflammation.2.To examine the expression patterm of AQP-5 in a rat model with CRS and explore its effects in succession of inflammation3.To evaluate the effect of glucocorticoids(GC)on AQP-5 in a rat model with CRS.Methods1.Animals(n=60)that underwent unilateral maxillary sinus ostial obstruction using Merocel nasal packing with standard staphylococcus aureus inoculation were examined for blood routine examination before operation and at 3 days,2,4,8 and 12 weeks after operation.Following sacrifice at 3 days,4,8 and 12 weeks,the obtained maxillary sinuses were prepared for histologic investigation and bacterial culture.Experimental interventions were compared with normal controls(n=12)and with contralateral control sinuses within each ani,al.2.The rats(n=44)were randomly divided into three groups:CRS group,dexamethasone(dexa)treatment group,control group.CRS group was sacrificed 4 weeksand 12 weeks postoperatively.On the 84th post-operative day,the dexa group received dexa(2 mg·kg-1·day-1)via intraperitoneal injection for 7 days.The controls did not receive any treatment.The expression of AQP-5 in the sinonasal mucosa was determined using imnunohistochemistry and quantitative PCR(qPCR).Immunohistochemical optical density values of AQP-5 were tested using ImagePro-Plus 6.0.Results1.White blood cell counts(wbc)at 3 days,2,4 and 8 weeks were significant higher than that of controls(p<0.01),peak at 2 weeks,while wbc at 12 weeks descend to the normal(p>0.05).Perforation of nasal septum,95.7%of the animals(44/46),was observed in 3 days,which almost located in anteroinferior nasal septum.Anatomical and histologic characteristics of chronic sinonasal inflammation were gradually present and stable from 4 to 12 weeks.The similar inflammation happened in the contralateral control sinuses within each animal as compared with the experimental sinuses.Standard staphylococcus aureus was detected in 36.4%bilateral sinuses at 4 weeks,while none at 12 weeks but conditional pathogenic bacterium in 66.7%bilateral sinuses.2.The immunoreactivities of AQP-5 were primarily noted in the epithelial lining and glandular cells,as well as in the vascular endothelium and goblet cells in the sinonasal mucosa.The AQP-5 mRNA expression level was significant higher in the dexa group than in the control and CRS groups(p=0.006 and p=0.014,respectively).However,no significant difference was found between the CRS and control groups(p=0.760).Immunohistochemical optical density values of AQP-5 in the dexa groupwas significant higher than in the control and CRS groups(p<0.05,respectively).Conclusions1.Unilateral maxillary sinus ostial obstruction using Merocel nasal packing with standard staphylococcus aureus inoculation results in a persistent,stable CRS in rat until 12 weeks after operation.No more evidence demonstrates that infection contributes to the persistence and stability of inflammation of CRS.2.AQP-5 noted in the epithelial lining and glandular cells maintains mucociliary transport.The upregulation of AQP-5 in the epithelial lining and the rest of glandular cells may reach equilibrium once more to help mucociliary clearance in the process of imflammation.3.Glucocorticoids induce AQP-5 expression in the sinonasal mucosa of CRS rats to improve the imflammation,which highlights AQP-5 as a potential target in the pathophysiology and treatment of CRS.