摘要目的 建立适合放射性肺损伤(RILI)CT灌注成像研究的兔动物模型.方法 健康新西兰大白兔48只,随机分为对照组(12只,做单肺假性照射)和实验组(36只,高能X射线单侧肺单次照射25 Gy),分别于照射后第1、6、12、24、48和72小时及第1、2、4、8、16和24周被处死,取两肺中带上、中、下野6处标本,分别进行HE染色光镜、电镜和局部肺组织TNF-α和TGF-β1的检测.结果 实验组所有兔受照射肺均产生了RILI,早期以急性炎性反应为主,晚期以进行性肺纤维化为特征.实验组受照射1 h后局部肺组织TNF-α表达、72 h后TGF-β1表达与对照组差异均有统计学意义(t=3.04～14.95,P＜0.05).光镜下,实验组受照射12 h后肺泡壁厚度、6 h后肺间质面积密度、24 h后间质内纤维母细胞和纤维细胞数量与对照组差异均有统计学意义(t=4.44～39.78,P＜0.05),并分别与照射后的时间直线相关(r=0.82、0.87、0.68).电镜下,实验组各时间点之间胶原纤维相对含量差异有统计学意义(F=100.31,P=0.000),对照组各时间点之间的差异无统计学意义.实验组受照射72 h后肺内胶原纤维相对含量与对照组差异均有统计学意义(t=3.07～45.18,P＜0.05),并与照射后时间直线相关(r=0.99).结论 25 Gy单肺单次高能X射线照射能制作稳定、可靠的兔RILI模型,较好地模拟了RILI的发生、发展的演变过程.

abstractsObjective To establish the rabbit model of radiation-induced lung injury (RILI) for the study of CT perfusion. Methods Forty-eight New Zealand rabbits were randomly divided into two groups, 36 rabbits in test group were administered with 25 Gy of single fractionated irradiation in the whole unilateral lung, and the other 12 rabbits in control group were sham-irradiated. All rabbits were sacrificed at 1, 6, 12, 24, 48, 72 h, and 1,2, 4, 8, 16, 24 week after irradiation respectively, then six specimens were extracted from upper, middle and lower fields of bilateral lungs, respectively. The pathological changes were observed with light and electron microscopies. The expression of TNF-α and TGF-β1 in local lung tissue was detected by immunohistochemistry. Results In test group, RILI occurred at early stage,characterized by acute inflammatory reaction, and featured by the progressing fibrosis at later stage. The expression of TNF-α and TGF-β1 1 and 72 h post-irradiation were statistically different between test and control groups (t = 3.04-14. 95,P ＜ 0. 05 ). Thickness of alveolar wall, density of pulmonary interstitium 12 h of post-irradiation, amount of fibroblast and fibrocyte from interstitium 24 h post-irradiation were statistically different between two groups ( t = 4.44-39. 78, P＜ 0.05 ), and correlated with the time postirradiation (r = 0. 821, 0. 872, 0. 682). There was statistical differences among the relative amount of collagen fibers at time points post-irradiation in test group ( F = 100.31, P ＜0.05), while no difference in control group ( F= 1.00, P ＜ 0.05 ). The relative amount of collagen fibers was statistically different between two groups 72 h post-irradiation (t = 3.07-45.18, P＜0.05 ), and correlated with the time postirradiation (r = 0.993 ). Conclusions Stable and reliable rabbit model of RILI could be established through single fractionated irradiation in whole unilateral lung with 25 Gy of high-energy X-rays, which may simulate the occurrence and development of evolution of RILI.