MiR-125b-5p通过靶向JAK2/STAT3信号通路轴影响肉鸡腹水综合征肺动脉重构的分子机制研究

肺动脉重构是肉鸡腹水综合征（AS）的重要病变体现之一。发现肺动脉重构发生发展的分子机制，寻找干预肺动脉重构发生发展方法对AS的防治具有重要意义。研究表明，miRNA对靶向mRNA调控作用与心血管疾病发生有着密切关系。但miRNA调控mRNA抑制肺动脉重构在AS中发生发展的分子机制尚未清楚。因此，基于申请者前期AS的肺动脉转录组测序结果显示STAT3基因被miR-125b-5p所调控，且参与了JAK2/STAT3关键信号通路轴。本项目选定miR-125b-5p为研究对象，采用miRNA干扰/过表达技术在肉鸡PVSMC和PAEC的单细胞与细胞共培养，再结合动物体内试验，验证miR-125b-5p调控STAT3在JAK2/STAT3中作用，以期阐明miR-125b-5p调控STAT3的表达与AS的肺动脉重构发生发展的分子机制，为开发防治AS的miRNA抑制药物研究提供新靶点。

Pulmonary artery remodeling in ascites syndrome (AS) in broilers is one important lesion in developing AS. Therefore, approaches of discovering the molecular mechanism and finding ways to interfere with the occurrence and development of pulmonary arterial remodeling is of great significance for improving the recovery rate of AS. Studies have shown that regulatory effects of microRNAs (miRNAs) on their target mRNAs are closely associated with cardiovascular diseases. However, the molecular mechanism of miRNAs regulation of mRNAs to inhibit the occurrence and development of pulmonary arterial remodeling in AS via target genes remains unclear. Our previous transcript results of the pulmonary arteries in the pre-AS model test have shown that STAT3 may be regulated by miR-125b-5p and participate in the crucial signaling axis of JAK2/STAT3 pathway. In this project, miR-125b-5p is selected as the research subject. Single-cell, cell co-culture and in-vivo experiments on broiler chicken pulmonary artery smooth muscle cells (PVSMC) and pulmonary artery endothelial cells （PAEC）are conducted using miRNA interference/overexpression techniques. Regulatory effects of miR-125b-5p on its target gene STAT3 in the JAK2/STAT3 signaling pathway axis are evaluated. The purpose of this study is to elucidate the molecular mechanism of miR-125b-5p regulating STAT3 expression and AS's pulmonary artery remodeling, and to provide new targeting objects for the development of drugs inhibiting miRNAs for the prevention and treatment of AS.