Background and purpose:Radiation-induced lung injury is a common complication in thoracic tumor after radiation therapy. How to protect the lung tissues from radiation injury is very important during radiotherapy. As a kind of radiation-protective agents, this study aimed to assess the protective effects of amifostine on acute lung tissues’ radiation-induced injury in the rats by radiated with chest wall tangent technology. Methods:Thirty-five female Fish-344 rats were randomized into 2 arms of 2 different fraction schedule:Conventional fraction, 20 rats were irradiated in 50 Gy per 25 fractions in 25 days. They were further randomized into 2 subgroups:10 with amifostine and 10 rats radiation alone without drug. Single fraction, 15 rats irradiated with 20 Gy in one fraction to the right lung. Three subgroups were randomized as:5 rats in irradiation plus amifostine;5 rats irradiation alone and 5 in control subgroup. Amifostine (140 mg/kg) was given intraperitoneally 30 minutes before irradiation. Breathing rate, weight variation and plasmas of transforming growth factor-β(TGF-β) 1 levels were recorded after irradiation. The lung tissue of irradiated side and the same side of control group were processed for hematoxylin and eosin staining, Masson’s and Weigen’s staining and TGF-β1 immunohistochemistry staining. Results:In both arms, breathing rate increased in rats got irradiated, however, the coming time of fastest breathing rate delayed in rats with amifostine. There is no difference among all subgroups of TGF-β1 level in the plasma. Hematoxylin and eosin staining and Masson’s and Weigen’s staining revealed alveolar wall became thicker and the pulmonary tissue fibrosis in irradiation alone group. However, in the radiation with amifostine group, no matter what schedule of fractionation, much more of the lung architecture was preserved and fibrosis was lessened. Immunohistochemistry staining was expressed positive to strongly positive in irradiation alone groups, but weakly positive to positive in irradiation with amifostine groups. In arm of conventional fraction group, compared with radiation alone group, weight loss in rats with amifostine used group was much more and had significant difference right after radiation initiated, but became closer when radiation finished. In arm of single fraction group, there was no significant difference of weight loss among 3 groups. Conclusion:This preclinical research showed amifostine can improve radiation-induced pneumonias symptoms, pulmonary alveoli hyperplasia and the pulmonary tissue fibrosis in rats either with conventional or single dose fractionation irradiation. Weight loss in rats with conventional fractionation may related to the side effect of amifostine with continuous apply.% 背景与目的：放射性肺损伤是胸部肿瘤放射治疗后的常见并发症,在放射治疗中如何保护肺组织免受或少受放射性损伤显得非常重要.本研究采用阿米福汀作为放射保护剂,探讨其对采用胸壁切线放射治疗技术照射大鼠肺组织放射性损伤的保护作用.方法：将35只雌性Fish-344大白鼠编号后按随机数字法分为常规照射部分和单次照射部分.常规照射部分：20只给予照射5周,总剂量为50 Gy,共25次.随机分为2组,用药照射组10只(随机照射左侧、右侧各5只)；对照照射组10只(随机照射左侧、右侧各5只).单次照射部分：15只右侧胸部切线单次照射20 Gy,随机分为用药照射组5只,对照照射组5只,空白对照组5只.用药照射组照射前30 min内腹腔注射阿米福汀(140 mg/kg),对照照射组用相同剂量照射.采用60Co治疗机,前后野半野对穿照射.照射结束后记录呼吸频率、体质量,尾静脉取血测转化生长因子-β1(transforming growth factor-β,TGF-β),取大鼠照射侧肺及对照组同侧肺进行TGF-β1免疫组织化学染色.结果：常规照射部分用药照射组在放射后4周呼吸频率达到最高,对照照射组在放射后2周达到最高,差异有统计学意义(P<0.05).单次照射部分对照照射组升高较用药照射组差异有统计学意义(P<0.05).常规照射部分及单次照射部分中用药照射组与单纯照射组各段时间内的血清TGF-β1差异无统计学意义(P>0.05).在常规照射部分,肺组织HE染色和马松染色显示,与正常肺泡壁比较,单纯照射组的肺泡壁明显增厚,其肺泡间质大部分为增生纤维组织和弹力纤维组织.而在照射加药组虽也有肺泡壁增厚和纤维化,但与单纯照射组相比较不甚明显,可见大部分肺泡结构存在,肺泡壁的纤维化增生较单纯照射组减轻.免疫组织化学TGF-β1染色显示正常组织为阴性或弱阳性的表达,单纯照射组的肺组织TGF-β1染色表达多为阳性或中强阳性,照射加药组表达为弱阳性或阳性.在常规照射期间,用药照射组在放疗开始后体质量明显下降,而对照照射组体质量下降不明显,差异有统计学意义(P<0.05),在放疗结束后两组之间的体质量平均值逐渐接近.单次照射部分3组之间体质量差异无统计学意义(P>0.05).结论：本研究显示,在单次大剂量照射部分和常规照射部分,阿米福汀可以改善大鼠受到照射后引起的肺部症状,改善了照射后肺部肺泡增生和纤维化程度.但是常规照射中连续应用阿米福汀会带来一定的不良反应,在实际应用中造成了大鼠体质量减轻.
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