SIRT1下调致肺泡Ⅱ型上皮细胞胰岛素敏感性降低促发晚期早产大鼠呼吸窘迫综合征

With remarkable improvements in healthcare in recent years，the natality of premature infants has increased than before，resulting in the same change of incidence of RDS year by year， especially the trend of RDS occured in late preterm infants is on the rise. As usual as its relatively large gestational age，RDS had always been ignored by clinicians in late preterm infants. So its mechanisms ，early prevention and treatment strategy has been more and more concerned. A large number of animal experiments and clinical observation showed that insulin resistance（IR）is associated with many lung diseases. Meanwile，our previous study found that the insulin signaling pathway was abnormal in lung tissue of late preterm births. On the top of theories，we intend to explore the relationship between insulin sensitivity of alveolar type 2 epithelial cells（AT-Ⅱ) with RDS in late premature rats，reveals the underlying molecular mechanisms，and find new pathogenic mechanism as well as molecular level site of NRDS. There may be significant for early diagnose，prevention and improvemen tof the remedy rate of NRDS.

近几年来医疗水平发展迅速，中晚期早产儿出生率明显增加，但因传统观念的影响，晚期早产儿发生RDS的病例往往被临床医生所忽略，而延误救治。因此晚期早产儿RDS的发生机制及防治策略逐渐成为关注热点。大量的动物实验及临床观察发现，胰岛素抵抗（IR）与许多肺部疾病如哮喘、肺动脉高压等相关。同时我们课题组前期研究发现晚期早产大鼠肺组织的胰岛素信号通路受损。本研究拟探讨肺组织胰岛素敏感性降低在晚期早产大鼠RDS发病中的作用，并探讨其机制可能与SIRT1下调导致肺泡Ⅱ型上皮细胞（ATⅡ）胰岛素敏感性降低有关，部分揭示其潜在分子机制。以拓展NRDS致病机制的认识，并发现新的分子调控靶点。对早期发现、预防及提高NRDS的救治成功率。

近几年来医疗水平发展迅速，中晚期早产儿出生率明显增加，但因传统观念的影响，晚期早产儿发生RDS的病例往往被临床医生所忽略，而延误救治。因此晚期早产儿RDS的发生机制及防治策略逐渐成为关注热点。大量的动物实验及临床观察发现，胰岛素抵抗（IR）与许多肺部疾病如哮喘、肺动脉高压等相关。本课题通过观察正常足月妊娠（阴性对照组）和妊娠糖尿病大鼠（阳性对照组）新生鼠的肺形态和功能发育，验证晚期早产大鼠肺组织存在胰岛素抵抗，与NRDS发生相关；通过ATII肺泡上皮细胞过表达SIRT1，可明显改善肺泡细胞胰岛素敏感性的同时，SP-A、SP-B的表达水平也显著提高，阐述晚期早产鼠的RDS可能与SIRT1下调导致肺泡Ⅱ型上皮细胞（ATⅡ）胰岛素敏感性降低有关，部分揭示其潜在分子机制。以拓展NRDS致病机制的认识，并发现新的分子调控靶点，对早期发现、预防及提高NRDS的救治成功率。