Study to control radiation lung damages.

由于肺部辐照的副作用，如肺纤维化和放射性肺炎，在辐照后6-12个月发生，因此需要较长的实验周期，以小鼠或大鼠进行此类副作用的研究。我们研究了阿加曲班对辐照后肺纤维化的影响。在加或不加阿加曲班治疗的情况下，大鼠右肺暴露于17 Gy电子辐射下。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。放射性肺炎通常见于受辐照区。然而，据报道，它有时发生在辐照区以外。这表明，不仅辐射引起的损伤，而且受辐射宿主的反应也可能引起放射性肺炎。此外，在细胞间粘附分子1 （ICAM-1）敲除小鼠中未观察到放射性肺炎，这表明受辐射宿主对放射性肺炎的免疫应答参与其中。为了探讨巨噬细胞在肺炎发生中的作用，我们在体外研究了巨噬细胞对电离辐射的反应。照射后1 ~ 2 h， IL-1 β和IL-6 mRNA显著升高，照射后4 h， IL-1 β和IL-6 mRNA显著降低。我们将研究(1)巨噬细胞中TNF- α的表达，据报道，TNF- α对组织损伤很重要；(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.