Han Guang, Zhou Yun Feng, Zhang Ming Sheng, Cao Zhen, Xie Cong Hua, Zhou Fu Xiang, Peng Min, Zhang Wen Jie
Department of Radio-Chemotherapy, Zhongnan Hospital and Cancer Research Center, Wuhan University, Wuhan, HB 430071, China.
Radiat Res. 2006 May;165(5):546-52. doi: 10.1667/RR3543.1.
Pulmonary fibrosis is a common delayed side effect of radiation therapy, and it has a poor prognosis. Tgfb1 is a potent chemoattractant for fibroblasts and stimulates the production of collagen, the protein that contains hydroxyproline. Since collagen is by far the most abundant protein in the lung, comprising 60-70% of the tissue mass, analysis of the hydroxyproline content in lung tissues provides a reliable quantitative index for pulmonary fibrosis. Thus hydroxyproline and Tgfb1 may be involved in the development of fibrosis. In this study, we investigated radiation-induced pulmonary fibrosis in a mouse model. C57BL/6 mice were assigned into four groups: no treatment, treated with Angelica sinensis treated only, X-irradiated only (a single fraction of 12 Gy to the thorax), and Angelica sinensis treatment plus radiation. We assayed expression of hydroxyproline and the mRNA and protein of Tgfb1 in the four groups. We found that Angelica sinensis down-regulated the production of Tgfb1 and hydroxyproline in mice with radiation-induced pulmonary fibrosis. This study has demonstrated for the first time that Angelica sinensis inhibits the progress of radiation-induced pulmonary fibrosis, possibly by down-regulating the expression of the proinflammatory cytokine Tgfb1. These data suggest that Angelica sinensis may be useful in preventing and/or treating radiation-induced pulmonary fibrosis in the clinic.
肺纤维化是放射治疗常见的迟发性副作用,且预后较差。转化生长因子β1(Tgfb1)是一种对成纤维细胞有强大趋化作用的因子,可刺激胶原蛋白的产生,胶原蛋白是一种含有羟脯氨酸的蛋白质。由于胶原蛋白是肺中含量最为丰富的蛋白质,占组织质量的60%-70%,因此分析肺组织中的羟脯氨酸含量可为肺纤维化提供可靠的定量指标。所以羟脯氨酸和Tgfb1可能参与了纤维化的发展过程。在本研究中,我们在小鼠模型中研究了辐射诱导的肺纤维化。将C57BL/6小鼠分为四组:未治疗组、仅用当归治疗组、仅进行X射线照射组(单次胸部照射12 Gy)以及当归治疗加辐射组。我们检测了四组中羟脯氨酸的表达以及Tgfb1的mRNA和蛋白。我们发现当归可下调辐射诱导的肺纤维化小鼠中Tgfb1和羟脯氨酸的产生。本研究首次证明当归可能通过下调促炎细胞因子Tgfb1的表达来抑制辐射诱导的肺纤维化进程。这些数据表明当归在临床上可能有助于预防和/或治疗辐射诱导的肺纤维化。