The Role Of Activation, Secretion, And Apoptosis Of Lung Fibroblastic In Radiation Lung Injury

Thoracic tumors such as lung cancer, breast cancer, lymphoma is the most widespread malignant tumor and is one of the supreme cause of death in china. Radiation-induced pulmonary pneumonitis and fibrosis secondary is a major limiting factor in the successful treatment of thoracic tumors. The disease afflicts millions of individuals worldwide and there are no effective therapeutic approaches. The radio-oncologists have focused on the molecular mechanisms through which growth factors could play a role in the development of Radiation-induced pulmonary injury, and wish to get the key targets to prevention and cure the diseaseRadiation-induced pulmonary reactions have classically been viewed as distinct phases-acute pneumonitis and, later, fibrosis-occurring at different times after irradiation and attributed to different target cell populations. As yet our understanding of disease pathogenesis is still controversial. It has been demonstrated that Radiation-induced pulmonary pneumonitis develops to be pulmonary interstitial fibrosis ultimately. Intraluminal fibrosis is one of the major characteristics of Radiation-induced pulmonary pneumonitis and is associated with recruitment of inflammatory cells , particularly fibroblast , macrophages , neutrophils and lymphocytes.We think the key to future success in developing useful treatment strategies for the disease will be to focus on developing a more complete understanding of the fundamental molecular mechanisms. In this research a single-dose of 30Gy irradiation of right hemithorax and sham right lung irradiation in Wistar rats was delivered and then sacrificed respectively at 1d, 7d, 14d, 28d, 56d and 84d. The values will be measured at different stages, including clinical manifestation, immunohistochemistry for a-SMA,TGF-β,MMP9,Bcl-2 and Bax. Meanwhile interferon-γ(IFN-γ) will be admoved experimentally to explore whether IFN-γwill degrade the radiation injury .The results are as the following:(1) The express of a-SMA in Fibroblast increased after irradiation. It demonstrate that the activation the FB after irradiation.(2) The express of TGF-6,MMP-9 in Fibroblast increased after irradiation. The result proved that the externalization of FB. As we all known,TGF-6 was the important biology excitatory transmitter during the activation. We suspected that FB could be the target cell to prevention and cure the radiation induced lung injury;(3) The increased express of Bcl-2 and the decreased express of Bax proved the counteract apotosis of FB. We suspect that should be correlation with the excessus proliferation;(4) Early intervention with IFN-γcould inhibit the secretion of a-SMA,TGF-8,MMP9. Then we suspect IFN-γcould prevent the development of alveolitis but not fibrosis of lungs in radiation induced pulmonary injury rats. The machanism was unknown as yet.