摘要
目的：探讨大鼠肺组织照射后,凝血、抗凝血系统改变,组织缺氧状况等微循环障碍表现导致放射性肺损伤的相关作用机理。
方法：本研究分通过建立大鼠放射性肺损伤模型进行相关的实验研究。采用60Co治疗机产生的Y线单次照射大鼠的右肺,照射剂量分别为0 Gy、7.0 Gy、14.4Gy,观察时间点为照射后1天(以下以d表示)、7天(d)、30天(d)和90天(d),180天(d),取对照组及各照射组大鼠的肺组织进行相关检测,包括：①大鼠放射性肺损伤的病理学观察,包括大体肉眼病变、H-E及masson染色,光学显微镜进行观察；②免疫组织化学方法检测肺组织TM、PAI-1及HIF-1a的表达水平。
结果：①肺组织的肉眼改变：对照组大鼠肺组织表面光滑,粉红色,弹性良好。照射组可见片状出血,水肿及肿胀。7.0Gy组及14.4Gy组照射后90d,可见肺组织表面有白色斑点,照射后180d,14.4Gy组大部分肺组织变成白色或灰白色,肺弹性差,体积缩小。②光镜下的病理学改变：照射后1d、7d,7.0Gy组大鼠肺泡腔及间隔可见轻微渗出、充血和水肿；14.4Gy组大鼠肺泡腔及间隔可见渗出、充血、水肿和炎性细胞浸润,局部见红细胞渗出；照射后30 d,7.0Gy组大鼠肺泡腔及间隔出现轻微水肿和炎性细胞浸润；14.4Gy组见肺泡间隔增宽、水肿、炎性细胞浸润和出血,并可见胶原形成；照射后90 d,14.4Gy组肺泡间隔进一步增宽,局部仍见出血,部分肺泡腔塌陷、不张,并且出现胶原形成；照射后180d,14.4Gy组,出现明显的胶原形成和纤维化改变。③TM的表达,与对照组比较,7.OGy组,除照射后1d有显著差异(P<0.05)外,其余各时点均无统计学差异(P>0.05)；14.4Gy组,除7d外,其余各时点均有统计学差异(P<0.05)。PAI-1的表达,与对照组比较,7.0Gy组,除照射后第90,180天外,其余各观察时点均有显著差异(P<0.05)；14.4Gy组在各观察时点均有显著差异(P<0.05)。HIF-la的表达,与对照组比较,7.0Gy组,除照射后1d有显著差异(P<0.05)外,其余各时点均无统计学差异(P>0.05)；14.4Gy组,1d、90d、180d均有显著差异(P<0.05),且逐渐表达上调。
结论：①肺组织受照射后,持续的促凝功能亢进和抗凝作用下降,是进展至肺纤维化的关键过程。②放射性肺纤维化过程中,组织缺氧是血管损伤后和后期纤维化形成的伴随改变和必然结果,并非起主导作用。③微循环障碍的进行性加重是放射性肺炎到肺纤维化的主要致病机理。
AIM To investigate the mechanisms of radiation-induced lung injury based on the microcirculation dysfunction performance including the changes of coagulation, anti-coagulation system and tissue hypoxia.
METHODS AND MATERIALS Wistar 75 rats were irradiated to the right hemithorax with a single dose of OGy,7.OGy,14.4Gy. Serial studies were performed before and 1,7,30,90,180 days after irradiation. Histological studies were carried out to detect histological changes in the pulmonary after irradiation.immunohistochemistry assay was to detect the expression of TM, PAI-1, HIF-la.
RESULTS In control group and 7.0Gy groups, there were no notable hispathological changes, just including little tissue exudates, congestion, edema and infiltration of inflammatory cells, red blood cell leakage. However, the inflammation was more obviously and the formation of collagen and fibrosis could be observed in 14.4Gy group.Compared with the control group, there was no difference of the expression of TM in 7.OGy group except lday.However, there was statistically significant in 14.4Gy group except 7 days. The expession of PAI-1 were difference in 7.0Gy group before 90days. Otherwise, there was statistically significant in 14.4Gy group at all time points. The expression of HIF-la was negative or weak positive in control and 7.OGy group.The expression of HIF-la had statistical significance atl,90,180 days after radiation, and also it was increased after 90 days.
CONCLUSION Firstly the coagulation and anti-coagulation system changes persistently after radiation which was primary factor of radiation firbrosis. Secondly,tissue hypoxia may be no an important factor in the process of pulmonary fibrosis, it maybe the result of the later peride of radiation-induced lung injury. Thirdly when more than "threshold" dose of radiation, the microcirculation dysfunction was the main mechanism of radiation-induced lung injury.
引文
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