氨磷汀与放射性肺损伤中肺剂量体积因素V_(20)的关系

Relationship between amifostine and lung dose volume factor V_(20) in radiation-induced lung injury

目的建立氨磷汀干预下^(60)Co-γ放射性肺损伤大鼠模型,并探讨氨磷汀在放射性肺损伤剂量体积因素V_(20)=25%和V_(20)=35%条件下发生肺损伤的作用。方法雄性SD大鼠随机分为空白组、模型组Ⅰ(照射V_(20)=25%)、模型组Ⅱ(照射V_(20)=35%)、药物干预组Ⅰ(氨磷汀+照射V_(20)=25%)、药物干预组Ⅱ(氨磷汀+照射V_(20)=35%)。模型组、药物干预组用^(60)Co-γ射线对大鼠右肺进行照射,于照射后第1,2,4,8和12周末处死大鼠,腹主动脉取血,ELISA法测定血清中转化生长因子β1(TGF-β_1)含量;同时间点取照射后肺组织,HE、Massons染色观察肺组织的病理损伤变化。结果与空白组比较,模型组大鼠肺泡壁增厚,肺泡间质大部分为增生纤维组织和弹力纤维组织,血清TGF-β_1显著升高(P<0.05);与模型组比较,大鼠肺组织在药物干预组(V_(20)分别为25%和35%)出现肺泡壁增厚和纤维化的时间滞后且程度轻,仍见大部分正常肺泡结构,且血清TGF-β_1明显降低(P<0.05);模型组Ⅱ中大鼠肺组织病理损伤和血清TGF-β_1均高于模型组Ⅰ,而其在药物干预组Ⅰ和Ⅱ之间未见显著改变。结论氨磷汀能减轻放射性肺损伤发生的概率,对V_(20)限定值可适当提高。

Objective To establish an animal model of lung ^（60）Co-γ radiation injury caused by amifostine and to investigate the effect of amifostine on lung injury in the lung dose volume factor 25% and 35%. Methods SD male rats were randomly divided into control group,model group Ⅰ（ radiation with V_（20）= 25% and no amifostine）,model group Ⅱ（ radiation with V_（20）= 35% and no amifostine）,drug intervention group Ⅰ（ radiation with V_（20）= 25% and amifostine）,and drug intervention group Ⅱ（ radiation with V_（20）= 35% and amifostine）. The rats in model groups and drug intervention groups were irradiated with ^（60）Co-gamma on the right lung. The blood and irradiated lungs from rats were collected at the end of 1,2,4,8 and 12 weeks after irradiation. The levels of transforming growth factor-beta 1（ TGF-β_1） were determined using ELISA. The pathological damage of lung tissues was assessed using HE and Massons staining. Results The alveolar wall was thicker,and there was more hyperplasia fibrous tissues and elastic fiber tissues in the alveolar interstitial in model groups than in control group. The levels of TGF-β_1 in model groups were increased significantly compared with control group（ P 〈0. 05）. The appearance time of the thicken alveolar wall and lung fibrosis in drug intervention groups（ V_（20）= 25% and 35%） was lagged compared with model groups. Moreover,the pathological damage of lung tissues in drug intervention groups was slighter than that in model groups. The levels of TGF-β_1in drug intervention groups were decreased compared to model group（ P 〈0. 05）. The degree of pathological injury in model group Ⅱ was more severe than that in model group Ⅰ. The levels of TGF-β_1 in model group Ⅱ were higher than those in model group Ⅰ. However,the degree of pathological injury and the levels of TGF-β_1 showed no significant difference between drug intervention groups Ⅰ and Ⅱ. Conclusion Amifostine can reduce the incidence of radiationinduced lung injury and the amifostine may appropriately increase the V_（20） limit value.