Roxithromycin inhibited airway inflammation through pathway of inducible nitric oxide synthase and nitric oxide in rat asthmatic model / 中国药理学通报

ABSTRACT

Aim To investigate the effect of roxithromycin on expression of inducible nitric oxide synthase (iNOS) and content of nitric oxide(NO) and cytokines(IL-4,IFN-?) in bronchiole epithelial cell of asthmatic rats.Methods Twenty four male Sprague-Dawley rats were randomly divided into three groups,namely control group,asthmatic group and roxithromycin group. The numbers of total cell and eosinophils cell in bronchoalveolar lavage fluid (BALF) were counted. The expression of inducible nitric oxide synthase was detected by immunohistochemistry method,and iNOS mRNA was detected by reverse transcription-lolymerse chain reaction (RT-PCR). The activity of iNOS and content of NO in lung homogenates were measured by spectrophotometry.The concentrations of IL-4 and IFN-? were detected by sandwich enzyme-linked immunosorbent assay (ELISA).Results The numbers of eosinophils cell and the ratios of eosinophils to total cell in BALF of asthmatic group[(7.28?1.65)?108?L-1,(7.73?1.54)%]were significantly higher than those of control group[(3.76?0.97)?108?L-1,(1.27?0.60)%],but those of roxithromycin group[(5.68?0.95)?108?L-1,(5.54?1.53)%]were lower compared with asthmatic group. The concentration of IL-4,activity of iNOS and content of NO in lung homogenates of asthmatic group were significantly higher than those of control group,while those of roxithromycin group were lower compared with asthmatic group. The concentration of IFN-? in lung homogenats of asthmatic group was significantly lower than that of control group,while that of roxithromycin group were higher compared with asthmatic group. The absorbance of iNOS protein expression in bronchiole epithelial cell and mRNA expression in lung homogenats of asthmatic group[(0.25?0.06),(0.52?0.14)]were markedly increased compared with control group[(0.14?0.05),(0.33?0.05)],while those of roxithromycin group[(0.15?0.03),(0.35?0.07)]were decreased compared with asthmatic group.Conclusions Roxithromycin can affect the concentrations of IL-4,IFN-? and the pathway of iNOS/NO in airway of asthma rat,through which inhibit asthmatic airway inflammation reaction.