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目的 比较不同剂量与不同剂量率的放射线对小鼠肺纤维化程度的影响.方法 近交系C57BL/6小鼠24只使用随机数字表法分为对照组6只和照射组18只,照射组进行小鼠全肺单次照射,按射线剂量和剂量率分为3组:A组:射线剂量15 Gy,剂量率400 cGy/min;B组:射线剂量20 Gy,剂量率400 cGy/min;C组:射线剂量20 Gy,剂量率100 cGy/min,对照组实施假照射.所有小鼠于照射后20周进行肺部CT扫描,处死并取肺组织,分别用HE、苦味酸天狼猩红染色在光镜下观察小鼠肺组织病理变化和纤维化程度,并进行Ashcroft纤维化评分,酸水解法来测定羟脯氨酸含量,实时荧光定量PCR检测Ⅰ型胶原mRNA表达,α平滑肌动蛋白免疫组织化学法观察肺组织中肌成纤维细胞的分布和积累.结果 与对照组比较,照射组小鼠的肺组织病理改变显示,照射后存在明显的肺实变和胶原沉积.各组小鼠照射20周后肺纤维化评分分别为A组(3.27 ±0.87)分,B组(5.18±1.12)分,C组(4.91±1.37)分,各组与对照组[(0.93±0.24)分]相比均明显增高,差异有统计学意义(t=-6.445,-7.998,-6.943,P＜0.05).结论 在剂量率不变的情况下,照射剂量越高,小鼠肺纤维化程度越重,而剂量相同时,剂量率增加对纤维化程度没有明显影响.

Objective To study the effect of radiation dose and dose rate on radiation-induced pulmonary fibrosis in mice.Methods Twenty-four C57BL/6 mice were randomly divided into a control group (n =6) and an irradiation group(n =18).The irradiation group was further assigned to 3 subgroups according to the whole lung radiation with 15 Gy at 400 cGy/min,20 Gy at 400 cGy/min and 20 Gy at 100 cGy/min,while the control group received sham-irradiation.All mice were scanned with computed tomograph (CT) 20 weeks post-irradiation,and then they were sacrificed and lung tissues were collected.H&E staining,sirius red staining,lung fibrosis scored and hydroxyproline content analysis were used to assess lung fibrosis and collagen deposition.Real time PCR was used to measure the mRNA expression of type Ⅰ collagen.Immunohistochemical staining was used to detect the activatin and distribution of a-SMA +-myofibroblasts.Results Compared to the control group,mice from irradiation groups exhibited significant pulmonary consolidation and collagen deposition.At the same dose rate,the higher irradiated dose used,the more severe pulmonary fibrosis was.On the other hand,with the same dose,the dose rate had less effect on pulmonary fibrosis.Conclusion The effect of radiation dose on the degree of pulmonary fibrosis in mice is more than effect of the dose rate.