pneumocytes, increases in capillary permeability, interstitial edema, alveolar capillary congestion and the accumulation of inflammatory and immune cells from peripheral blood in the alveolar space. radiation pneumonitis may trigger multiple repair mechanisms to restore lung function and remodel
نویسندگان
چکیده
radiation-induced lung injury (rili) is one of the most common and severe side effects of thoracic radiotherapy. Therefore, novel therapeutic approaches to improve the effectiveness of rili treatment are required. The present study was designed to determine the effectiveness of a traditional chinese medicine regimen, Shenqi Fuzheng injection (SFi), in the treatment of rili. SFi is composed of extracts from codonopsis pilosula and radix astragali. Here, we determined the protective effects of SFi on rili with a single-dose irradiation (rT) of 12 Gy in c57Bl/6 8-week-old mice. The mice were divided into four groups treated with i) phosphatebuffered saline (PBS; pH 7.4, 20 ml/kg/day) alone as normal a control; ii) SFi only (20 ml/kg/day); iii) rT + PBS (20 ml/ kg/day); and iv) rT + SFi (20 ml/kg/day). SFi and PBS were administered via intraperitoneal injection 1 week before and 2 weeks after rT. The pathology of rili and any clinical signs of toxicity were monitored. The expression of tumour necrosis factor (TnF)-α and transforming growth factor (TGF)-β1 in the lungs was analyzed by rT-Pcr and immunohistochemistry. TnF-α and TGF-β1 expression was increased by rT, but was reversed by SFi treatment during the radiation pneumonic and fibrotic phases (P<0.05). Lung histology at 24 weeks revealed a significant decrease in structural damage and collagen deposition in the rT + SFi group compared to the rT + PBS group. in conclusion, TnF-α and TGF-β1 are key mediators for the pathogenesis of rili, and SFi reduces TnF-α and TGF-β1 expression after rT. This may be a key mechanism behind the preventive effects of SFi on lung injury after radiation. Introduction Pulmonary radiation is an important curative and palliative modality in the treatment of thoracic cancer, but is often associated with toxicity to neighbouring normal tissues, which limits the deliverable dose intensity (1). The radiosensitivity of lungs represents a critical late toxicity issue after radiation therapy; clinical manifestations of lung toxicity, termed radiation-induced lung injury (rili), mainly include radiation pneumonitis and lung fibrosis. RILI is the most common and most severe side effect of thoracic radiotherapy (2-4). it is usually unavoidable, seriously affects the quality of life of patients, and suggests a poor prognosis (5). The incidence of rili is 10-20% (6); 50-100% of patients with rili develop radiological evidence of regional lung injury, while 50-90% experience a decline in pulmonary function (7). early rili manifests as radiation pneumonitis, occurs between 1 and 3 months of radiation, and is characterized by the loss of type i pneumocytes, increases in capillary permeability, interstitial edema, alveolar capillary congestion and the accumulation of inflammatory and immune cells from peripheral blood in the alveolar space. radiation pneumonitis may trigger multiple repair mechanisms to restore lung function and remodel lung fibrosis (8-10). The duration (hours to days) before the obvious appearance of radiation pneumonitis is referred to as the ‘latent’ period, since no clear histopathologic signs are observed. if radiation pneumonitis develops, it leads to pulmonary fibrosis characterized by the loss of capillaries, thickened alveolar septa and obliteration of the alveolar space. The clinical symptoms of rili are characterized by cough, dyspnea and fever. Several studies have shown that pro-inflammatory cytokines play direct and indirect roles in the development of rili (11-13). Tumour necrosis factor (TnF)-α and transforming growth factor (TGF)-β1 are among the most crucial pro-fibrosis cytokines. TNF-α and TGF-β1 expression is elevated in lung tissue after irradiation (12,14,15). Therefore, in this study, TnF-α and TGF-β1 were used as biomarkers to evaluate the effects of rili treatment. although several agents have been used for the treatment of rili (including glucocorticoid, angiotensin-1-converting Modulation of radiation-induced tumour necrosis factor-α and transforming growth factor β1 expression in the lung tissue by Shengqi Fuzheng injection Xiao-ronG donG, JinG-na WanG, li liu, Xue cHen, MinG-SHi cHen, Juan cHen, JinG-Hua ren, Qin li and Jun Han cancer center, union Hospital, Tongji Medical college, Huazhong university of Science and Technology, Hubei 430022, P.r. china received January 25, 2010; accepted april 19, 2010 doi: 10.3892/mmr_00000306 Correspondence to: Professor li liu, cancer center, union Hospital, Tongji Medical college, Huazhong university of Science and Technology, Wujiadun 156, Jianghan, Wuhan, Hubei 430022,
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