Studies On The NF-?B Signal Pathway In Radiation-induced Lung Injury

Objective To discuss the role of TNF-?and related NF-?B signal pathway in radiation-induced lung injury,that might get a new insight into the pathogenesis of RILI and help to find new potential therapeutic measures.Methods Forty-eight SD rats were randomly divided into two groups:control group?A?and 16Gy irradiation group?F?,n=24 in each group.The models of RILI in SD rats were established by irradiating with a single dose of 0Gy?sham?or 16Gy over their right hemithoraces using ⁶⁰Co?therapeutic machine.All rats were sacrificed at 2,5,12 and 24 weeks post-irradiation,the pathological changes of the lung were observed by hematoxylin-eosin?HE?staining and Masson staining;content of hydroxyproline in lung tissues was detected by UV spectrophotometer;the expression of transforming growth factor?1?TGF-?1?,tumor necrosis factor??TNF-??,nuclear transcription factor-?B p65?NF-?B p65?and interleukin-10?IL-10?were detected by immunohistochemistry;theinterleukin-10?IL-10?in serum was detected by enzyme-linked immunosorbent assay;the expression of phosphorylation NF-?B p65 and NF-?B p65 were detected by western blotting.Results?1?The histological results of lung tissue in rats:the lung tissue of rats was intact in the control group at all time point after irradiation.The 16Gy radiation groups showed that displayed hyperemia,edema and inflammatory cell infiltration in the lung tissue at 2 and 5 weeks post-irradiation,and showed thickening of alveolar walls and pulmonary fibrosis in the lung tissue in it at 12and 24 weeks post-irradiation.?2?the content of hydroxyproline in lung tissue:with the extension of time after irradiation,the HYP in the lung tissue of rats in16Gy group increased gradually,when cpmpared with that in group A p<0.05.?3?The expression level of TNF-?protein in the lung tissue of rats:it's little positive expression of TNF-?in lung tissue of rats in the control group,and the TNF-?in group F was increasing after irradiation,in lung tissue of rats in the group A and F two groups to have statistical sense?p<0.05?.?4?The expression level of NF-?B p65 protein in lung tissue of rats:?1?immunohistochemical results:prolonged after irradiation,the expression of NF-?B p65 in lung tissue showed a trend of increasing first and then decreased and finally increased again.In the 16Gy irradiation group?F?increased rapidly at 2th weeks post-irradiation and reached to the peak at 5th weeks,and it falled at 12 and 24 weeks.And it in the 16Gy irradiation group was higher than in the control group at each time point after irradiation?p<0.05?.?2?Western blotting results:the expression of NF-?B p65 in the group F was higher than in the control group at each time point after irradiation?p<0.01?.And it in the group F increased at 2th weeks post-irradiation and reached to the peak at 5th weeks,falled at 12 and 24 weeks.Comparison between time points,p<0.05.?5?The expression of NF-?B p-p65proteins:prolonged after irradiation,the expression of NF-?B p-p65 in lung tissue showed a trend of increasing first and then decreased and increased again.In the 16Gy irradiation group,it increased at 2 weeks and reached the maximum at 5 week,then decreased at 12 weeks,and increased at 24 weeks.Comparison between time points has statistical?p<0.05?.?6??1?Th expression of IL-10proteins in lung tissue of rats:prolonged after irradiation,the expression of IL-10 in lung tissue showed a trend of increasing first and then decreased.On the second week after irradiation,a large number of positive cells were found in the 16Gy irradiation group and it reached the maximum at 5 week,decreased at12 and 24 weeks,which was lower than that of the second week.?2?The serum levels of IL-10:it was higher in the 16Gy irradiation group than the control group at each time point after irradiation,p<0.05.And it increased at 2 weeks,reached the maximum at 5 weeks,decreased at 12 and 24 weeks,but was higher than the group A.Comparison between time points has statistical?p<0.05?.?7?The expression level of TGF-?1 proteins:the expression of TGF-?1 in the group R was higher than in the control group at each time point after irradiation?p<0.05?.It increasd with the prolongation of time after irradiation.Conclusions?1?TNF-?,NF-?B p65,IL-10,TGF-?1 take part in the development of radiation pneumonitis and fibrosis,and TNF-?,NF-?B p65,IL-10 play a role in the acute stage of RILI.?2?TNF-?-NF-?B signal pathway is activated in the course of RILI,and the NF-?B signal pathway is involved in the acute stage of RILI.