Circ_0006880/circ_0007785通过miR-125b-2-3p调节CASP1促进细胞焦亡参与肛门直肠畸形发病机制的研究

先天性肛门直肠畸形（anorectal malformation，ARM）是小儿外科常见疾病，术后排便功能障碍严重影响患儿生活质量及心理健康。本课题前期发现细胞焦亡依赖的CASP1及circ_0006880/circ_0007785在ARM发生的关键期的表达升高；生物学预测发现circ_0006880/circ_0007785可通过miR-125-2-3p调节CASP1表达，促进炎性因子释放，改变微环境，导致大鼠胚胎泄殖腔膜尿生殖隔融合异常及盆底肌、肠神经系统发育不良。本课题拟利用乙烯硫脲致畸的ARM大鼠模型、肠上皮细胞、肌卫星细胞、胎鼠羊水等，通过免疫组化/荧光、双荧光素酶、ELISA及Fish等技术在体内外实验中探索circRNA对CASP1表达的调控机制，细胞焦亡与ARM发生及盆底肌、肠神经系统发育的关系，对揭示ARM发病机制有重要意义，为ARM临床干预及治疗研究提供新思路。

Anorectal malformation (ARM) is a common disease in pediatric surgery. Postoperative defecation dysfunction seriously affects children's quality of life and mental health. In the early stage of this project, it was found that the expression of CASP1 which is dependent on pyroptosis, and circ_0006880 / circ_0007785 were significantly increased in the critical period of ARM. Circ_0006880 / circ_0007785 regulate CASP1 expression through miR-125-2-3p by biological prediction, promoting the release of inflammatory factors , accelerating cell death, changing the microenvironment, resulting in abnormal fusion of the clonal membrane and urogenital septum of the embryo , and dysplasia of the pelvic floor muscles and enteric nervous system. This project intends to use ARM rat model with ethylene thiourea, intestinal epithelial cells, muscle satellite cells and amniotic fluid, through immunohistochemistry / fluorescence, dual luciferase, ELISA and Fish and other technologies, in vitro and in vivo experiments, to explore the regulatory mechanism of circRNA on CASP1 and the relationship between pyroptosis and the pathogenesis of ARM, the development of pelvic floor muscles and enteric nervous system. It is of great significance to reveal the pathogenesis of ARM and provide new ideas for clinical intervention and treatment of ARM.