| Objective:By observing the influence of intranasal treament with P110δ blockers (IC87114) on the expression of NF-KB and interleukin-17in lung tissue of asthmatic mice, explore the mechanism of p110δ, NF-KB, IL-17in asthma pathogenesis and multual relationship, and thus provide a theoretical basis for a new approach to asthma treatment. Methods:40Balb/c mice were randomly divided into asthma group (X), azithromycin intervention group (A), blank control group (K), the IC87114high-dose intervention group (Y1), IC87114small-dose intervention group (Y2). The asthma group:each mouse was sensitized by intraperitoneal injection of0.2ml antigen suspension allergens (chicken ovalbumin OVA100ug,aluminum hydroxide2mg, saline0.2ml)in the first day, the8th day, the15th day.Inspire mices by intranasally instill40ulOVA solution in each mice after0.75%pentobarbital anesthesia in the16th day and repeated it for7days. Azithromycin intervention group:each mice sensitized as the asthma group, then was teated with intraperitoneal injection of azithromycin (50mg/kg)30minutes before inspired.The IC87114intervention group:each mice sensitized as the asthma group, then was given inhibitor by intranasally instill1hour before inspired at the16th day,the18th dayand and3hours after inspired at the21st day.The high-dose and the small-dose were lmg/kg.d,0.1mg/kg.d. Blank control group:each mice was sensitized intraperitoneal injection of0.2ml saline on the first day,the8th day,the15th day.Then they were inspired with saline for7days. All mice were sacrificed after the last stimulation in48hours Cut lung tissue and HE staining to evaluate the organization’s general morphology and cell infiltration; measure the content of IL-17, PIP3in serum by enzyme-linked immunosorbent assay (ELISA); detect the expression of NF-KBp65in lung tissue using immunohistochemistry; test IL-17mRNA amount in lung tissue of mice by RT-PCR.All data was expressed by (x±s).One-way ANOVA of variance was used in the study to analyze.Pairwise comparisons use the SNK test, if the heterogeneity of variance use theTamhanei France. Analysis the linear correlation of IL-17and IC87114in Serum using Pearson rank correlation method of Bivariate process. Statistic all data by SPSS13software.Results:(1) lung tissue pathohistologic:X group, a large number of inflammatory cell were infiltrated in small airways and small blood vessels.There was edema in mucosa and red blood cell appeared in alveolar space.The inflammation was obsorbed in the Yl, Y2and A group,and the Y1group was more obvious.The alveolar structures were clear inflammation cells exudate were decreased in alveolar lumen and alveolar interstitial,and the bronchial epitheliums were almost integrity.There was no inflammation in control group.(2) The expression of NF-KBp65in lung tissue:the NF-KBp65expression,by immunohistochemistry, was strongly positive in X group,but was negative in K group.There were positive expression of NF-KBp65in Y1, Y2,and A group,in which Y2group was stronger while the Y1group was weaker.(3)The expression of IL-17and PIP3in serum1) the IL-17content:each group of content from high in the end, respectively, are X, Y2, A, Y1, K. The difference between the five groups was statistically significant (P<0.05), followed by multiple comparisons between groups and by pairwise comparisons, the difference was statistically significant (P<0.05);2) the PIP3content:Are the same to IL-17.(4) The expression of IL-17mRNA in lung tissue:X group was the highest while the K group was the lowest. By pairwise comparison, the difference was statistically significant (P<0.05).Conclusions:(1)P110δ inhibitor IC87114can inhibit the asthma airway inflammation,and the NF-KB activation, IL-17expression.(2) PI3K/AKT pathway may regulate IL-17to mediated asthma airway inflammation through the activation of NF-KB. |
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