Study to control radiation lung damages.

由于肺放射治疗的副作用，如肺纤维化和放射性肺炎，在照射后6-12个月发生，需要长时间的实验来研究这些副作用。将大鼠的右肺暴露于17戈伊电子辐射，用或不用阿加曲班处理。阿加曲班治疗组大鼠肺纤维化不严重，侵入肺的吞噬细胞数量明显少于未治疗组大鼠。放射性肺炎通常发生在照射部位。然而，据报道，它有时发生在照射区域之外。提示放射性肺炎的发生不仅是辐射损伤所致，而且受照者自身的反应也可能引起。细胞间粘附分子1（ICAM-1）基因敲除小鼠未出现放射性肺炎，提示受照宿主的免疫应答参与了放射性肺炎的发生。为了研究巨噬细胞在肺炎发展中的作用，我们研究了巨噬细胞对体外电离辐射的反应。照射后1-2 h，IL-1 β和IL-6 mRNA表达显著增加，照射后4 h，IL-1 β和IL-6 mRNA表达显著降低。我们将研究（1）TNF- α在巨噬细胞中的表达，据报道这对组织损伤很重要，以及（2）HGF和阿加曲班对肺损伤的保护作用。

Because side effects of lung irradiation, such as lung fibrosis and radiation pneumonitis, occur 6-12 months after irradiation, long experiment period is required for investigation on such side effects using mice or rats.We investigated effects of Argatroban on lung fibrosis after irradiation. Right lungs of rats were exposed to 17 Gy electron radiation with or without treatment with Argatroban. In the group of rats treated with Argatroban, lung fibrosis was not severe and the numbers of phagocytes invading into the lungs were significantly less compared with those in the non-treated group of rats.Radiation pneumonitis is usually observed in the irradiated area. However, it has been reported that it sometimes occurs outside the irradiated area. This suggests that not only radiation-induced damage but also the reaction of the irradiated host may cause radiation pneumonitis. Furthermore, radiation pneumonitis was not observed in the intercellular adhesion molecule 1 (ICAM-1) knockout mice, which suggests the involvement of immune response of the irradiated host to radiation pneumonitis. To investigate the role of macrophages in the development of pneumonitis, we investigated the response of macrophages to ionizing radiation in vitro. Significant increases of IL-1 β and IL-6 mRNA were observed 1-2 hours after irradiation, and significant decreases of these mRNA were observed 4 hours after irradiation. We will investigate (1) the expression of TNF- α in macrophages, which is reported to be important for tissue damage, and (2) the protective effects of HGF and Argatroban against lung damage.