目的从补骨脂单体化学成分中筛选抗哮喘的小分子化合物,并阐释其抗哮喘作用机制。方法基于IL-4在哮喘病理中的作用,采用IL-4-GFP转基因报告小鼠(4get鼠)和流式细胞术,设计一种抑制白细胞介素-4(IL-4)产生的抗哮喘药物筛选新方法。结果与DMSO组相比,异补骨脂查尔酮能显著抑制Th2细胞中IL-4的产生(P〈0.001),减少转录因子GATA-3的表达(P〈0.01),降低信号转导与转录激活因子STAT6磷酸化水平(P〈0.01)。结论异补骨脂查尔酮通过抑制STAT6磷酸化而减少GATA-3的表达,从而抑制IL-4的产生,其具有开发成为治疗哮喘药物的潜力。
Objective To screen the small molecular compounds with anti-asthma activity from Psoralea corylifolia monomor and explain its regulation mechanism.Methods Based on the effect of IL-4 in pathological features of masthma,a high throughput screening system was designed by using 4get mice and flow cytometry to inhibit IL-4 production so as to anti-asthma.Results Compared with DMSO group,isobavachalcone showed high ability of inhibiting IL-4 production in Th2 cells(P < 0.001),down-regulating GATA-3 expression(P < 0.01),and decreasing the level of STAT6 phosphorylation(P < 0.01).Conclusion Isobavachalcone could inhibit the IL-4 production through down-regulating the GATA-3 expression by controling the level of STAT6 phosphorylation.Isobavachalcone is a potential drug for the treatment of asthma.