曲尼斯特对大鼠放射性肺损伤干预作用.docVIP

曲尼斯特对大鼠放射性肺损伤干预作用 　 作者：谢聪颖，张薛榜，吴式琇，李凡凡，官 静，郑举奖，陈锡文 【摘要】 ［目的］ 观察曲尼斯特（Tranilast）对放射性肺损伤大鼠的转化生长因子β1（TGF-β1）及Ⅰ、Ⅲ型胶原蛋白表达的影响。 ［方法］ 65只Wistar大鼠分为3组，曲尼斯特治疗照射组（实验组25只），单纯照射组（单照组25只），以及空白对照组（空白组15只）。照射后不同时间分别检测血浆TGF-β1含量，光镜下观察右肺组织形态学变化及免疫组化检测TGF-β1及Ⅰ、Ⅲ型胶原蛋白表达。［结果］ 实验组较单照组肺泡炎和纤维化出现晚且程度轻；照射后2个月TGF-β1表达比单照组降低（P=0.002）；Ⅰ型胶原蛋白（从照射后3个月开始），Ⅲ型胶原蛋白（从照射后2个月开始）在实验组的表达明显低于单照组（P=0.001）。血浆TGF-β1检测显示，实验组的TGF-β1含量高峰延至照射后第3个月。［结论］ 曲尼斯特通过降低TGF-β1表达有效地减轻了放射性肺损伤；对减少Ⅰ、Ⅲ型胶原沉积有同等的作用，提示其潜在的抗肺纤维化治疗作用。 【关键词】 曲尼斯特 Effect of Tranilast on Radiation-Induced Lung Injury in Rats Abstract: ［Purpose］ To investigate the effect of Tranilast on expressions of TGF-β1, type Ⅰ and Ⅲ collagen induced by radiation lung injury in rats. ［Methods］ Sixty-five Wistar rats were divided into 3 groups: irradiation and Tranilast treatment group (experimental group), 25 rats; irradiation alone group, 25 rats; and control group, 15 rats. Level of TGF-β1 in plasm was detected at different time points. Expression of TGF-β1, typeⅠand Ⅲ collagen was detected immunohistochemically. Morphological characteristics in right pulmonary were observed microscopically. ［Results］ Compared to irradiation alone group, the appearance of alveolitis and fibrosis was delayed and mild, and TGF-β1 expression was significantly lower in 2 months after irradiation in experimental group (P=0.002). TypeⅠcollagen (3 months after irradiation) and Ⅲ collagen deposition(2 months after irradiation) in experimental group significantly decreased compared with irradiation alone group（P=0.001）. The peak of TGF-β1 in plasm was delayed until the third month after radiation in experimental group. ［Conclusion］ Tranilast alleviates radiation-induced lung injury via down-regulating TGF-β1 expression, as well as reducing biosynthesis of type I and Ⅲ collagens. It suggests that Tranilast is provided with therapeutic potential as an antifibrotic agent. Key words: Tranilast; radiation-induced lung injury;therapy 放射性肺损伤是胸部肿瘤放射治疗的常见并发症，临床上有效治疗措施少，疗效不满意，严重影响患者的预后和生活质量。糖皮