肺功能分析在放射性肺损伤防治药物药效评价中的作用

摘要

目的：探讨肺功能分析在放射性肺损伤防治药物药效研究中的意义。方法采用30只C57BL／6小鼠以20 Gy的X线行小鼠胸部单次照射，照射后给予地塞米松[给药组按4．5 mg／（ kg· d）的剂量给予地塞米松磷酸钠注射液，2周后减半维持至1个月]，对照组和模型组给予等体积生理盐水。照射后1个月，使用EMKA肺功能分析系统在清醒状态下行肺功能测试，随后活杀取材，HE染色观察肺组织结构变化，应用Image-pro图像分析软件分析肺泡腔面积。结果给药1个月后，模型组及地塞米松组小鼠肺功能部分指标，如50％呼气流量、每分通气量、呼气峰值、吸气峰值、潮气量较对照组明显降低，但地塞米松组较模型组降低程度有所减轻。肺组织病理变化示，地塞米松组小鼠肺泡腔面积减小程度、肺间质中性粒细胞浸润程度均较模型组有所减轻，与肺功能分析结果相符。结论地塞米松对放射性肺损伤具有一定治疗效果；肺功能分析与肺组织病理变化相结合印证，可以有效评价放射性肺损伤防治药物的药效。%Objective To explore the role of pulmonary function analysis in drug efficacy evaluation of radiation-induced lung injury.Methods Totally 30 C57BL/6 mice were randomly divided into 3 groups:control group, radiation group and dexamethasone group.Mice in radiation group and dexamethasone group were irradiated with 20 Gy X-ray on the whole chest.Then mice in dexamethasone group was intraperitoneally injected with dexamethasone at the dose of 4.5 mg/( kg· d) for 2 weeks and then the dose was halved up to 1 month after radiation while control group and radiation group were intraperitoneally injected with 0.9%saline.One month after irradiation, pulmonary function of all the mice was tested with EMKA system.Then mice were sacrificed and pathological changes of pulmonary tissue were observed by HE staining. Furthermore, the area of alveolar cavity was measured with the Image-pro plus software.Results One month after irradiation, the pulmonary function parameters of mice in radiation and dexamethasone groups, such as mid-expiratory flow, minute volume,tidal volume,peak inspiratory flow,and peak expiratory flow,decreased obviously compared with the control group, but those parameters of the dexamethasone group decreased much less significantly than in the radiation group.The pathological changes of pulmonary tissues showed that the area of alveolar cavity of radiation group and dexamethasone group was smaller than that of the control group, but the extent of the loss of alveolar cavity area of the dexamethasone group was less than in the radiation group.Neutrophils infiltration could be found in the radiation group and dexamethasone group, but was less serious in the dexamethasone group.The result of pulmonary function analysis was coincident with pathological changes of the lung.Conclusion Dexamethasone can alleviate radiation induced pulmonary injury.Pulmonary function analysis combined with pathological observation of pulmonary tissues can effectively evaluate the efficacy of drugs in radiation induced lung injury.