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The Observation Of Radiation-Induced Pulmonary Injury In Rats By Different Dose Fractionation

Posted on:2012-12-09Degree:MasterType:Thesis
Country:ChinaCandidate:K YuanFull Text:PDF
GTID:2154330332494272Subject:Radiation Therapy Oncology
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Objective To establish animal models of radiation-induced pulmonary injury by different dose fractionation. We want to detect the changes of TGF-β1, TNF-α, ACE in serum, observe the radiation-induced pulmonary injury pathological changes in rats, discuss TGF-β1, TNF-α, ACE in serum on the acute radiation-induced pneumonitis and late stages of chronic pulmonary fibrosis, and study the differences of radiation-induced lung injury in different dose fractionation.Methods Using male Wistar rats of SPF level, the right lungs of rats were radiated by 60Coγ-ray. Ninety Wistar rats were randomly divided into experimental A group (Low-dose fraction irradiation group), B group (High-dose fraction irradiation group), and control group (which were not been radiated). We sampled blood and right lungs in rats after irradiation in the 1st, 3rd, 5th, 10th and 24th week. The TGF-β1, TNF-α, ACE in serum were measured by ELISA technique. We observed the histological changes of their right lungs with HE staining from 1st week to 24th week after irradiation.Results1. High-dose fraction irradiation group, TGF-β1 in serum increased after being radiated, and it reached a peak in 10th week. TGF-β1 in serum remained at high level from 5th week to 24th week; After being radiated, TNF-αin serum increased rapidly from 1st week and reached the peak in 10th week, then declined rapidly; After being radiated, the ACE in serum declined to bottom in 10th week, and then it recovered quickly.2. Low-dose fraction irradiation group, TGF-β1, TNF-αin serum increased after irradiation, but the changes were less than that of High-dose fraction irradiation group;ACE in serum decreased slowly after irradiation, and then it increased rapidly to peak at 10th week, which higher than control group.Finally, ACE in serum decreased to normal level.3. The model with High-dose fraction irradiation, ACE in serum was lower than Low-dose fraction irradiation group and control group at any time. The model with Low-dose fraction irradiation, ACE in serum was lower than control group at any time except the 10th week.4. The pathological changes in pulmonary tissue have experienced a process from acute radiation-induced pneumonitis to chronic pulmonary fibrosis, including acute inflammation period, hyperplasia period, and fibrosis period. Whether the acute radiation-induced pneumonitis or the radiation-induced pulmonary fibrosis, the Low-dose fraction irradiation group is lighter than the High-dose fraction irradiation group.5. With the extent of acute radiation injury gradually increased, the TGF-β1, TNF-αexpression levels adding. When radiation-induced pneumonia showed the most severe, the TGF-β1,TNF-αexpression levels increased to the highest point. At the periods of late fibrosis, TNF-αdecreased rapidly, but TGF-β1 remained at high levels.Conclusions TGF-β1, TNF-αin serum and the lung injury have a close relationship. With TGF-β1, TNF-αgradually adding, the pulmonary tissue pathological injury increased. TNF-αplays an active role in acute inflammation, which caused by radiation-induced lung injury, and TGF-β1 not only plays a role in acute inflammation but also plays an important role in fibrosis, which caused by late-stage damage. Received the same total doses of irradiation, Low-dose fraction irradiation group has less histological changes and the contents of TGF-β1, TNF-αin serum than High-dose fraction irradiation group, Low-dose fraction irradiation can protect late response tissue. The ACE in serum is negatively associated with acute radiation-induced pneumonitis, ACE can monitor the repair situation of pulmonary vascular endothelial cells after radiation injury. The model of 2Gy fractionated irradiation, which total doses are 30Gy, is safe to the right pulmonary irradiation.
Keywords/Search Tags:Transforming growth factor-β1 (TGF-β1), Tumor necrosis factor-α(TNF-α), Radiation-induced pulmonary injury, serum, Enzyme-linked immunosorbent assay (ELISA)
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