RESUMO
Asthma is a heterogeneous disease that affects three hundred million people worldwide. About half of them are not well controlled, new therapeutic approach and more effective medicines are therefore urgently needed. Recent studies have shown that bitter taste receptors (Tas2rs) are expressed in respiratory system, and Tas2rs might be used as new targets for asthma treatment since some bitter compounds show therapeutic potential for asthma therapies. Based on this situation, we studied the effect of bitter compound baicalin (BA) on the apoptosis of inflammatory cells in the respiratory tract of asthmatic mice and its relationship with bitter signal transduction. Male BALB/c mice were selected as the tested animals randomly divided into control group (CK), asthma mouse model group stimulated by intraperitoneal injection and aerosol inhalation of ovalbumin(OVA) and intragastric administration of BA intervention OVA-induced asthma group (OVA + BA). The results showed that inflammatory cells infiltration, alveolar septum thickening and diminished alveolarspaces were observed in the OVA group after HE staining. The above symptoms were significantly alleviated in OVA+BA group. The total number of inflammatory cells and classified cell count in the bronchoalveolar lavage fluid of mice in OVA group were increased, and the number of inflammatory cells in BA intervention group were decreased significantly (P < 0. 05). Analysis of real-time quantitative PCR showed that the expression levels of mucin Muc5ac were significantly increased in the lung in OVA group (P <0. 05), while the expression levels of Muc5ac in OVA+BA group were significantly lower than that in OVA group (P <0. 05). The expression of Tas2r108, Tas2r126, Tas2r135, Tas2r143 and their downstream signal transduction molecules α-gust and Trpm5 were down-regulated in OVA group (P < 0. 05). In OVA group, the transcription of pro-apoptotic factors P53, Bax and Casp3 was inhibited, and decreased activity of caspase3 was detected, whereas the transcription of anti-apoptotic factor Bcl2 was up-regulated (P < 0. 05). In OVA+BA group, the transcription of tested Tas2rs genes and downstream signal transduction molecules (P < 0. 05), as well as pro-apoptotic genes P53, Bax and Casp3 were all up-regulated associated with the decreased Bcl2 expression and increased caspase3 activity (P < 0. 05). Our results suggest that BA might function as a bitter taste receptor agonist to mediate the regulation of respiratory tract inflammatory cells apoptosis by activating the bitter signal transduction system, and thus to reduce the lung inflammation and injury in asthmatic mice.
RESUMO
Because the large number of people is suffering from asthma, and about half of them are not well controlled, new therapeutic approach and more effective medicines are therefore urgently needed. Recent studies have shown that bitter taste receptors (T2Rs) are expressed in various tissues, and T2Rs might be used as the new targets for asthma treatment since some bitter compounds show therapeutic potential for asthma therapies. In this study, the relationship between the development and exacerbation of asthma and bitter signal transduction was analyzed by establishing the asthma model in the C57BL/6 mice. The present results showed that the total number of white blood cells and the number of eosinophil, neutrophil, lymphocyte and macrophages in the bronchoalveolar lavage fluid (BALF) were significantly increased (P < 0. 05), accompanied with the up-regulation of Muc5ac gene expression (P< 0. 01) and asthma-like pathologically changes in mice lungs in OVA or OVA+SO