早期肺纤维化在极重度骨髓型放射病中启动机制的探讨

Exploration of initiation mechanism of early pulmonary fibrosis in extremely severe hematopoietic type of radiation sickness

目的探讨极重度骨髓型放射病早期肺纤维化发生机制,以及与照射剂量和存活时间的关系。方法从两例尸检病例取材制片,进行HE、免疫组化包括TGFβ、-αSMA、Ⅳ型前胶原、MMP-9和天狼猩红染色。结果107病例TGFβ信号位于肺泡巨噬细胞,-αSMA信号出现于肺平滑肌和巨噬细胞,少数Ⅱ型上皮可见微弱的Ⅳ型前胶原和MMP-9阳性信号;而在108病例,增生的成纤维细胞TGFβ信号阳性,肌成纤维细胞-αSMA阳性,肺泡间隔出现较多的Ⅰ、Ⅲ型胶原,Ⅱ型上皮可见较强的Ⅳ型前胶原和MMP-9信号。结论极重度骨髓型放射病人肺内可表达TGF-β,促进成纤维细胞转化,产生Ⅰ、Ⅲ型胶原;其程度与照射剂量成反比,与存活时间成正比。

Objective To explore pathogenetic mechanism of early pulmonary fibrosis in extremely severe hematopoietic type of radiation sickness and its relation to irradiation dose and surviving time of the patient. Methods Autopsy of two cases of radiation sickness was performed and conventional histopathological sections of lung tissue were prepared, which were stained immunohistochemically for TGFβ, α-SMA, precollagen Ⅳ, MMP-9 and Sirius red. Results In one case, the TGFβ-positive signal was located in alveolar macrophages, α-SMA signal appeared in smooth muscle cells and macrophages, weak procollagen Ⅳ and MMP- 9 signals displayed in a small number of type Ⅱ epithelial cell. In another case, the TGFβ signal was located in proliferating fibroblasts, α-SMA signal displayed in myofibroblasts, a lot of collagen Ⅰ and Ⅲ signals appeared in thickened alveolar septa, and a strong positive signals of procollagen Ⅳ and MMP-9 could be seen in type Ⅱ epithelal cell. Conclusion TGF-β can be expressed in lung tissue of patients with hematopoietic type of radiation sickness and promote fibroblasts to transform into myofibroblasts. Collagen I and Ⅲ can be produced at alveolarseptum, which extent is in inverse ratio to radiation dose and in direct ratio to surviving time of the patient.