miR-150-5p在溃疡性结肠炎激素抵抗中的作用机制研究

溃疡性结肠炎（ulcerative colitis,UC）发病率逐年增高，机制未明治疗困难，而糖皮质激素抵抗患者是治疗难点。本小组通过microRNA PCR芯片及qRT-PCR筛选发现miR-150-5p表达下调，提示其与UC激素抵抗相关。目前国内外尚无miR-150-5p与UC激素抵抗的研究，本项目通过：①检测miR-150-5p在UC激素治疗前、后表达，明确激素对其表达的影响；检测miR-150-5p在激素敏感和抵抗哮喘、肾病综合征、系统性红斑狼疮表达，明确其在UC激素抵抗的特异性；荧光素酶报告基因实验检测靶基因；②过表达和沉默干预THP-1细胞miR-150-5p表达，在细胞水平揭示其在UC激素抵抗中的作用机制；③建立miR-150-5p敲除小鼠UC模型，研究其对激素治疗效果的影响及机制。旨在明确miR-150-5p在UC激素抵抗的分子机制，为治疗激素难治性UC提供新的理论依据。

The morbidity of UC in China is increasing year by year and its pathogenesis is still unclear. The treatment of UC is a difficult point, especially in patients with glucocorticoid resistance. Our team found differential expression of microRNA by microRNA PCR microarray and qRT-PCR in UC patients with glucocorticoid resistance. Our preliminary research results revealed that miR-150-5p were decreased expression in UC patients with glucocorticoid resistance, which prompted that there was some correlation between miR-150-5p and glucocorticoid resistance. However,there is no any study about the relation between microRNA-150 and glucocorticoid resistance. So we make a plan to find out this correlation. Firstly, to detect the expression of miR-150-5p in the serum of UC with glucocorticoid resistance before and after treatment to determine whether the glucocorticoid had an effect on the expression of miR-150-5p. Then, we detect the expression of miR-150-5p in the serum of asthma, nephrotic syndrome, systemic lupus erythematosus with glucocorticoid sensitive and resistant to assess whether it is the characteristic of UC with glucocorticoid resistance. The target gene of miR-150-5p was detected by luciferase reporter gene experiment. Secondly, to reveal the mechanism of mir-150-5p in UC with glucocorticoid resistance at a cellular level by overexpression and silent interference means in THP-1 cells. Finally, to study the mechanism of miR-150-5p in glucocorticoid resistance by UC experiment animal disease model using miR-150-5p knockout genetic engineering mice. In brief, the aim of this study was to clarify the molecular mechanism of glucocorticoid resistance of miR-150-5p in UC with glucocorticoid resistance and to provide a new theoretical basis for the treatment of refractory UC.