Analysis of molecular mechanism and development of preventive methods against the radiation-induced lung fibrosis

放射性肺纤维化的分子机制分析及预防方法开发

基本信息

批准号：
20790922
负责人：
KATOH Hiroyuki
金额：
$ 2.33万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2009
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20790922/
关键词：
「放射線,X線,粒子線」「放射線」「トランスリレーショナルリサーチ」「放射線防護」「放射線肺臓炎」放射線,X線,粒子線放射線トランスリレーショナルリサーチ放射線防護放射線肺臓炎放射線, X線, 粒子線

项目摘要

Radiation-induced lung injury is one of the major dose-limiting factors of radiotherapy for thoracic malignancies such as lung and breast cancers. Radiation-induced lung fibrosis develops several months to years after radiation exposure at least in the irradiated field. Moreover, there are non-negligible critical risks of developing generalized lung fibrosis that is usually life-threatening. Although many studies have tried to analyze the mechanisms underlying the pathogenesis of radiation-induced lung fibrosis, the mechanisms still remain unclear. Hence, the prevention of radiation-induced lung fibrosis is difficult to realize in a clinical set- ting although extensive efforts have been undertaken in the exploration of this condition. The present study examined whether Ulinastatin reduced radiation-induced lung fibrosis in C57BL/6J mice, the standard mouse strain for studying the pathophysiology of radiation-induced fibrosis. In addition, the therapeutic potential of Ulinastatin was analyzed for prolongation of the lifespan of mice irradiated with a significant dose for inducing lung fibrosis. The present study clearly indicated that administration of Ulinastatin reduced radiation-induced lung fibrosis in mice, and timing and the injection timing of Ulinastatin for irradiation was important. It is noteworthy that the Ulinastatin administration period, which caused positive suppression of lung fibrosis, corresponded to the period of the increase in TGF-β level by irradiation, and especially before reaching the peak level of TGF-β. Therefore, it was suggested that the suppression of lung fibrosis might be due to the suppression of TGF-β by Ulinastatin.

辐射引起的肺损伤是胸腔恶性肿瘤的主要剂量限制因子，至少在辐射范围内辐射后几个月至数年。 - HE机制。辐射诱导的肺部的发病机理仍然不清楚肺纤维化。 Ulinastatin在C57BL/6J小鼠中辐射的辐射肺fiblis，用于研究辐射诱导的纤维化病理生理学的标准小鼠菌株。用明显的剂量诱导肺纤维化。在TGF-β水平上，尤其是在达到TGF-β的峰值之前，肺纤维的抑制可能是由于WY抑制TGF-β。