曲尼斯特对大鼠放射性肺损伤的干预作用

Effect of Tranilast on Radiation-Induced Lung Injury in Rats

[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。

[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 aud Tranilast treatment group （experimental group）, 25 rats; inadiation 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, type 1 and Ill collagen was detected immunohistochemieally. 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 mouths after irradiation in experimental group （P=0.002）. Type Ⅰ collagen （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 radiationinduced 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.