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Establishment Of Radiation-induced Lung Injury Model In Vitro And Vivo And Experimental Study Of Protective Effect Of FM0818 On Acute Irradiation-induced Lung Injury

Posted on:2010-04-23Degree:MasterType:Thesis
Country:ChinaCandidate:J M ZhangFull Text:PDF
GTID:2144360275475143Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Background and ObjectiveRadiation-induced lung injury is a common complication of thoracic radiotherapy. It has two clinical stages, one is radiation pneumonitis, and the other one is radiation pulmonary fibrosis. Its mechanism is complex. Currently were no specific effective prevention and treatment methods. It's necessary to establish a stable experimental model in order to investigate radiation-induced lung injury and screen protective drug. This study will establish irradiation-induced lung injury model in vitro and vivo, and observe the protective effect of curcumin derivant FM0818 on acute irradiation-induced lung injury.Methods(1) Murine RAW264.7 cells were irradiated with 8Gy X-ray to establish irradiation-induced lung injury model in vitro. TNF-αwas detected by ELISA and NF-кB,p53 were detected by Western Blot to estimate this model and investigate the mechanism.(2) The whole thorax of mice were irradiated with 18 Gy X-Ray to establish the pulmonary injury model of mice. CT scanning and image analysis of the mean gray value were carried out to acquire the data of each mouse after irradiation for 2, 6 and 12 weeks. The pathologic changes of lung were studied by the way of HE and Masson staining pathologic slice of lung.(3) Observe the protective effect of curcumin derivant FM0818 on acute radiation-induced lung injury. Results(1) After RAW264.7 irradiated with 8Gy X-ray, the release of TNF-αand the expression of NF-кB and P53 were increased in time-effect relationship.(2) The analysis of mean gray value indicate, after irradiation for 2, 6 and 12 weeks, compared with normal control, the mean gray value of the model group all increased, 2 weeks and 6 weeks increased obviously (P<0.01); The analysis of HE and Masson staining pathologic slice of lung indicate, compared with normal control, significant histological and pathologic changes were observed.(3) 0.125,0.25,0.5μg/mL of FM0818 can potently inhibited the release of TNF-αand induced the expression of NF-κB, p-p38, p53 in dose-dependent manners.Conclusions(1) It's possible to establish the radiation-induced lung injury model in vitro by irradiated with 8Gy X-ray on RAW264.7. The detection of TNF-αcan efficiently evaluate this model.(2) It's possible to establish the radiation-induced lung injury model of mouse with 18 Gy X-Ray radiation of whole thorax, and the new way of image analysis can efficiently evaluate the degree of the lung injury.(3) Curcumin derivant FM0818 have some preventive and therapeutic effects in the early time of the radiation pulmonary injury, and has dose-dependent manners. The mechanism may be associated with down-regulation of NF-κB, p-p38, p53 expressions.
Keywords/Search Tags:radiation-induced lung injury, model, curcumin derivant
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