Ghrelin保护放射性肺损伤及其机制研究

Radiation-induced lung injury (RILI) is a common and serious complication in the radiation therapy of lung cancer, which significantly restricts the radiation doses in tumor radiotherapy, and complicates the quality of life of cancer patients. The prevention and treatment of RILI have long been a clinical challenge.In our previous studies, we confirmed that the expression of ghrelin in the lung was decreased in RILI mice model. Ghrelin, which was subcutaneously infused for 6 weeks using an osmotic mini-pumpthe, effectively prolonged animal survival and alleviated the lung injury. Otherwise, we revealed that ghrelin inhibited the radiation-induced ROS and DNA damage, and the radiation-induced abnormal autophagy and apoptosis. Current research evidence and our previous work indicate that (1) Ghrelin may alleviate radiaion-induced ROS production via supressing the expresion of Rac1 and NOX1/4;(2) Ghrelin may protect aganist apoptosis via inhibiting abnormal autophagy. In the further study, we will complete the preliminary studies and determine the exact mechanism of grelin in regulation of ROS production and autophagy through the combination of overexpression and RNA interference experiments. Our study may provide new avenue for the prevention and treatment of RILI in clinic.

放射性肺损伤（RILI）是肺癌放疗常见及严重并发症，限制肿瘤靶区的放疗剂量，影响患者生活质量，目前尚缺乏有效治疗手段。Ghrelin一种促生长激素释放的脑肠肽，我们的前期工作证实，小鼠全肺照射后，肺组织中Ghrelin水平降低；皮下渗透微泵缓释给予Ghrelin可以有效提高小鼠生存率，减轻肺损伤。初步结果显示Ghrelin可以抑制放射线诱导的ROS升高及DNA损伤；并抑制放射线引起的过度自噬及凋亡。基于文献报道及我们的前期工作，推测：Ghrelin一方面可能在分子水平通过抑制Rac1及NOX1/4蛋白减少ROS的产生，进而减轻DNA损伤，另一方面可能在亚细胞水平抑制过度自噬，发挥抗凋亡作用。本课题将完善前期研究，结合过表达或RNA干扰实验，在体内外明确Ghrelin调控ROS及自噬的分子信号通路。本课题研究有望为RILI的防治提供新的思路及方法。

放射性肺损伤（RILI）是肺癌放疗常见及严重并发症，限制肿瘤靶区的放疗剂量，影响患者生活质量，目前尚缺乏有效治疗手段。Ghrelin一种促生长激素释放的脑肠肽，我们的工作证实，小鼠全肺照射后，肺组织中Ghrelin水平降低；皮下渗透微泵缓释给予Ghrelin可以有效提高小鼠生存率，减轻肺损伤及纤维化。进一步研究显示Ghrelin一方面在分子水平通过抑制Rac1蛋白，而非NOX1/4蛋白，减少ROS的产生，进而减轻DNA损伤及肺损伤，改善小鼠生存，另一方面可能通过非Beclin1依赖的通路，在亚细胞水平抑制过度自噬，发挥抗凋亡作用。本课题研究有望为RILI的防治提供新的思路及方法。