miR-29c调控胰岛素样生长因子1在深低温停循环后的肠道损伤内源性保护机制的研究

项目名称： miR-29c调控胰岛素样生长因子1在深低温停循环后的肠道损伤内源性保护机制的研究

项目编号： No.81470578

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 吉冰洋

作者单位： 中国医学科学院阜外医院

项目金额： 68万元

中文摘要： 深低温停循环（DHCA）后肠道并发症发生隐匿，一旦发现难以逆转。充分认识DHCA对肠道的损伤及肠道自身修复机制，从而早期诊断、早期干预是防治肠道并发症的核心。前期DHCA后大鼠肠道组织芯片结果显示miR-29c显著下调，靶基因预测结果提示：胰岛素样生长因子1（IGF-1）很可能是miR-29c的调控靶点，而IGF-1可抑制细胞凋亡, 并促进修复。课题组提出在DHCA引起炎症和缺血再灌注损伤时，肠道下调miR-29c以提高IGF-1表达，减轻损伤，促进修复这一全新内源性保护机制假说。在细胞和动物水平验证miR-29c对IGF-1的靶控关系，和miR-29c调节IGF-1对肠道的内源性保护机制。从临床角度研究DHCA患者血浆内miR-29c与肠道并发症的相关性，探讨miR-29c作为潜在生物标记物的可能性。最终为DHCA后肠道损伤的预防、诊断和早期保护性干预提供理论基础与全新思路。

中文关键词： 体外循环；微小RNA；心血管外科

英文摘要： Intestinal complications after deep hypothermia circulatory arrest (DHCA) are difficult to diagnose and life-threatening. The key problem of early diagnosis and intervention is to fully recognize the intestinal injury and repair mechanism after DHCA. The microRNA expression pattern of intestinal tissue of rats underwent DHCA showed significantly decrease of miR-29c. The results of microRNA targets prediction indicated that insulin growth factor 1(IGF-1) might be the target gene of miR-29c. IGF-1 negatively regulates the apoptotic process and promotes intestinal restoration. We hypothesized a new endogenous protective mechanism that the miR-29c is down regulated and increases IGF-1 expression, to alleviate intestinal injury and promote restoration during DHCA . We will verify the regulating effect of miR-29c to IGF-1, and the protection to intestine and barrier function in vivo and in vitro. In consideration of the stability of microRNA, the miR-29c may be a potential biomarker of intestinal injury after DHCA. We will launch a clinical trial to investigate the relationship between plasma miR-29c and intestinal complications. Eventually we will achieve to provide theoretical basis and new ideas for prevention, diagnosis and therapy of intestinal injury after DHCA .

英文关键词： cardiopulmonary bypass;microRNA;cardiovascular surgery