尽管糖皮质激素（GCS）临床应用已60年，每年几十亿美元的销售额，但是在治疗过程中，病人对GCS产生抗性已成了该药物在临床上应用的瓶颈。目前克服GCS抗性的药物已取得一定的成功，但是这些药物的副作用限制了其临床使用。申请者先前研究结果揭示：GCS治疗白血病过程中，激活Stat3/miR-17-92信号途径是其产生抗性的关键因素。申请者基于以上发现构建了靶向Stat3/miR-17-92信号途径的活性物质的高通量筛选模型，并利用这个模型筛选出52个能增敏糖皮质激素的活性化合物。 本项申请将构建其它引起糖皮质激素抗性的miRNAs信号途径的筛选模型，并利用这些模型，对贵州民族药及源于其的化合物库进行系统研究，从中发现克服糖皮质激素抗性的活性物质，并对其作用机制进行深入研究。用活性化合物作探针，探讨与GCS抗性相关的新基因和新蛋白，且为开发贵州民族药新功效，使其走向国际药品市场提供科学理论依据。

Although Glucocorticoid (GCS) has been clinically used for 60 years and make billions of dollars every year. The resistance of GCS has limited its use in treatment. Currently, drugs overcome GCS resistance have made some progress, but the side effects of these drugs have restricted their clinical use. The applicant's previous results revealed that the activation of the Stat3/miR-17-92 signal pathway is a key factor in the leukemia cells resistance to GCS. Based on the findings, the applicant built a high-throughput screening model for active substances by targeting Stat3/miR-17-92 signal pathway, and used this model to obtained 52 compounds that can enhance leukemia cells sensitive to GCS. This application will build other screening model of miRNAs signal pathway that get involved in glucocorticoid resistance, and using these models to screen bioactive substance from Guizhou ethnic medicine and compounds derived from the ethnic medicine. The goal of this application is to discover the bioactive substances to overcome glucocorticoid resistance and study their mechanism. Using bioactive compounds as probes, applicant will uncover new genes and proteins related to GCS resistance, and this observation will provide a scientific evidence for the development new function of Guizhou ethnic medicine and expand its use in world .