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目的用大鼠放射性肺损伤模式评价阿米福汀对单次肺照射的放射性肺损伤保护作用和对TGFβ1活性变化的影响。方法34只150～160g的Fish344雌性大鼠随机进入照射加药(11只)、单纯照射(11只)、单用药(6只)和正常对照(6只)实验组。用4MVX射线单次28Gy照射右全肺,照射前30min腹腔内注射阿米福汀150mg/kg。每2周观测呼吸频率和血浆转化生长因子(TGFβ1)水平,在6个月后终止观察。肺组织进行羟脯胺酸、胶原蛋白含量、总TGFβ1与活性TGFβ1水平、TGFβ1蛋白表达和巨噬细胞量等检测。结果单纯照射组呼吸频率于第8周发生改变、达(185±13)次/min,3只因呼吸困难终止观察,7只有胸腔积液;照射加药组于第14周开始增加,仅为(125±5)次/min,无呼吸困难和胸腔积液发生。单纯照射组的肺组织结构消失纤维化,照射加药组也有纤维化,但保持大部分肺泡结构。血浆TGFβ1水平呈双峰改变,单纯照射组12周时为(3.2±0.5)ng/ml,较照射加药组(1.3±0.3)ng/ml明显增高(P=0.004);肺组织活性TGFβ1与总TGFβ1含量之比分别为3.9%±0.2%与3.1%±0.2%,单纯照射明显高于照射加药组(P<0.05)。结论阿米福汀不仅能增加肺组织对放射性损伤的耐受,同时也能减少TGFβ1的含量与表达,也许同时能减少TGFβ1的活性表达。
Objective To evaluate the protective effect of amifostine against radiation-induced lung injury induced by single lung irradiation and the effect of amifostine on the activity of TGFβ1 in rats with radiation-induced lung injury. Methods Thirty-four female Fish344 rats (150-160g) were randomly divided into experimental group (11 rats), irradiation alone (11 rats), single administration (6 mice) and normal control (6 mice). With a single 28Gy 4MVX ray irradiation right whole lung, 30 minutes before irradiation, intraperitoneal injection of amifostine 150mg / kg. Respiratory rate and plasma transforming growth factor (TGFβ1) levels were observed every 2 weeks and stopped after 6 months. Lung tissue hydroxyproline, collagen content, total TGFβ1 and active TGFβ1 levels, TGFβ1 protein expression and macrophages and other detection. Results In the irradiation group, the respiratory rate changed at the eighth week (185 ± 13) times / min. Three patients stopped their observation due to dyspnea and the other seven had pleural effusion. The radiation administration group began to increase at the 14th week, (125 ± 5) times / min, no dyspnea and pleural effusion occurred. The lung tissue structure of pure irradiation group disappeared fibrosis, irradiation plus drug group also had fibrosis, but maintained most of the alveolar structure. The levels of plasma TGFβ1 showed a bimodal change, which was significantly higher at (3.2 ± 0.5) ng / ml at 12 weeks than that at irradiation alone (1.3 ± 0.3) ng / ml (P = 0.004) The total TGFβ1 contents were 3.9% ± 0.2% and 3.1% ± 0.2%, respectively. The levels of total TGFβ1 were significantly higher than that of the irradiated group (P <0.05). Conclusion Amifostine can not only increase lung tissue tolerance to radioactive injury, but also reduce the content and expression of TGFβ1, and may also reduce the activity of TGFβ1 expression.