[关键词]
[摘要]
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。
[Key word]
[Abstract]
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.
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[基金项目]
国家自然科学基金杰出青年项目(30890143)