Effect of chicanine on Th1/Th2 imbalance and GATA-3 in asthmatic rats
Objective To explore the therapeutic effect and its mechanism of chicanine on the animal model of asthma.Methods Rats were randomly divided into 5 groups:control group,model group,low,medium,and high dose groups,with 12 rats in each group.Except control group,all rats in the other groups were given ovalbumin(OVA)to induce the asthma model.Rats in low,medium,and high dose groups were given 10,20 and 40 mg/kg chicanine,respectively,and the rats in control group and model group were administered with equal volume of 0.1％dimethyl sulfoxide(DMSO)solvent by gavage for 7 d.The morphological changes of lung tissue and goblet cell metaplasia were observed by hematoxylin eosin(HE)and periodic acid-Schiff(PAS)staining.The levels of interferon-y(IFN-γ),interleukin(IL)-12,IL-4,IL-5 and IL-13 in bronchoalveolar lavage fluid(BALF)were detected by ELISA.Th1/Th2 cell subsets in spleen were detected by flow cytometry.The relative mRNA expressions of E-cadherin,α-smooth muscle actin(α-SMA),N-cadherin and vimentin in lung tissue of rats were detected by qRT-PCR.The relative protein expressions of E-cadherin,α-SMA,N-cadherin,vimentin,p-p38(Thr180+Tyr182),p38,and GATA-3 in lung tissue of rats were detected by Western blot.Results Compared with model group,the morphology of lung tissue was improved in low,medium,and high dose groups,the secretion of inflammatory cells,goblet cells and mucus was decreased,the relative expressions of E-cadherin mRNA and protein in lung tissue were increased(P＜0.05),the relative mRNA and protein expressions of α-SMA,N-cadherin and vimentin were decreased(P＜0.05),the ratio of p-p38(Thr180+Tyr182)/p38 ratio and GATA-3/Histone H3 ratio were decreased(P＜0.05),the levels of IFN-γ and IL-12 and the IFN-γ/IL-4 in BALF were increased(P＜0.05),the levels of IL-4,IL-5 and IL-13 were decreased(P＜0.05),the number of CD4+IFN-γ+(Th1)cells and Th1/Th2 ratio in spleen were increased(P＜0.05),and the number of CD4+IL-4(Th2)cells was decreased(P＜0.05).Conclusion Chicanine has a significant therapeutic effect on asthmatic rats by correcting Th1/Th2 imbalance and downregulating p38-mediated GATA-3 phosphorylation in lung tissue of asthmatic rats.
chicanineasthmap38 mitogen activated protein kinase(MAPK)Th1/Th2GATA-3
国家科技期刊平台
NSTL
万方数据
