Objective:To investigate the regulatory mechanism of TGF-β/Smad signal pathway in the radiation-induced lung injury (RILI).Methods:144 male SD rats were randomly divided into six groups:normal control group (A),8 Gy irradiation group (B),10 Gy irradiation group (C),12 Gy irradiation group (D),14 Gy irradiation group (E),16 Gy irradiation group (F),24 mice in each group.The models of RILI in SD rats were established by irradiating with a single dose of 0 Gy (sham),8 Gy,10 Gy,12 Gy,14 Gy,16 Gy over right hemithorax using 60Co 7 therapeutic machine.At 2,5,12 and 24 weeks post-irradiation,five rats from each group were sacrificed.The pathological changes of lung tissue were evaluated by hematoxylin and eosin (HE) stains and Masson stains.Western blotting was performed to detect the protein expression of Smad2 and Smad7.Results:(1) The alveolar structure of lung tissue of group A was intact,and no obvious exudation and hyperplasia were observed.At the end of the 5th and 12th week after irradiation,pathologic changes in the lung tissue of all irradiated rats exhibited chronic inflammatory changes,manifested as lymphocyte infiltration,collagen deposition and fibrous tissue hyperplasia.At week 24 after irradiation,hyperemia and edema subsided in group B,C and D,lymphocyte infiltration was still visible in part of the lung tissue,pulmonary interstitial fibrosis were less compared to week 12.While in the group E and F,the tissue showed thickened significant alveolar wall,incomplete alveolar wall,more lymphocytes infiltration,and significant pulmonary interstitial fibrosis hyperplasia.(2) Compared to group A,the expression of Smad2 in the groups B,C,D,E peaked at 5 weeks,and fell at 12 and 24 weeks (P＜0.05).It also rapidly reached to the peak at 5th weeks also in the 16 Gy irradiation group F,but it did not fall at 12 and 24 weeks and was significant higher than those in other groups (P ＜ 0.05).The expression of Smad7 proteins were also increased at 2 and 5 weeks in all the irradiation group (P ＜0.05).It dropped sharply in groups B,C,D at 12 weeks (all P＜0.05),while it did not fall in groups E and F (all P＞0.05).Conclusion:The TGF-β/Smad signaling pathway plays an important role in the development of the radiation-induced lung injury.%目的:研究TGF-β/Smad信号通路在大鼠放射性损伤中的作用.方法:将144只健康雄性SD大鼠随机分为空白对照组(A组)和不同剂量8 Gy、10 Gy、12 Gy、14 Gy、16 Gy照射组(分别为B组、C组、D组、E组、F组),每组24只.采用60C0 γ射线放射治疗仪分别给予各剂量照射组大鼠进行右全肺照射,A组不作照射处理.于照射后第2、第5、第12、第24周末处死大鼠,取其右肺组织行苏木精伊红(HE)、Masson染色评价其病理改变;westen blotting检测大鼠肺组织中Smad2、Smad7蛋白表达.结果:(1)A组大鼠肺组织肺泡结构完整,未见明显渗出、增生;照射后第5、第12周末,所有照射组大鼠肺组织表现为淋巴细胞浸润为主的慢性炎症改变,且可见肺组织间胶原沉积、纤维组织增生;照射后第24周末,B组、C组、D组照射后充血、水肿消退,部分肺组织仍可见淋巴细胞浸润,肺间质纤维化较第12周减轻,而E组、F组则表现为明显的肺泡壁增厚,肺泡壁不完整,组织间仍有较多的淋巴细胞,肺间质纤维组织增生明显.(2)与A组比较,各照射组大鼠肺组织的Smad2、Smad7蛋白表达量在照射后第5周末均明显升高(均P ＜0.05),随后逐渐下降.与第5周末比较,B组、C组、D组、E组的Smad2蛋白表达量在第12、第24周末明显回落(均P ＜0.05),而高剂量的F组到第12、第24周末并未出现明显回落(均P＞0.05),且第24周末明显高于其他各组(均P＜0.05);同时,B组、C组、D组的Smad7蛋白表达量在第24周末也均大幅回落(均P＜0.05),但E组、F组却无明显下降趋势(均P＞0.05).结论:在大鼠放射性肺损伤中,Smad2、Smad7蛋白的变化与其肺组织病理改变一致,TGF-β/Smads信号通路参与调控大鼠放射性肺损伤的过程.
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