博莱霉素损伤早期EGF,TGF-β_1活性表达与肺泡泡炎病理分级

Active expression of EGF and TGF-β_1 and pathological grading of pulmonary alveolitis in early bleomycin induced pulmonary injuries

目的 定量测量小鼠肺泡炎肺泡灌洗液中 EGF,TGF-β1 的表达与同期肺泡炎的病理分级和肺泡 型细胞超微结构的变化间的关系 .方法 通过气管内滴注博莱霉素A5建立小鼠肺泡炎模型 ,按采集灌洗液的时间 (1,3,7d)分为 3组 ,分批直视下取肺泡灌洗液 ,采用夹心 EL ISA法定量检测灌洗液中 EGF,TGF- β1 表达 ,同时取各组的肺组织行常规 HE染色 ,光镜观察肺泡的病理变化及炎症分级 ,电镜观察肺泡 型细胞的超微结构变化 .结果实验组 EL ISA测定显示 :1,3,7d组肺泡灌洗液中 EGF的水平均低于正常对照组(P<0 .0 1) ,TGF- β1 的水平有所升高 ,但与正常对照组比较无显著性差异 .病理学检查显示 ,各组病变以 级肺泡炎为主 ,随病程进展逐渐向 , 级发展 ,肺泡 型细胞变性坏死以 3,7d组明显 .将 EGF和 TGF- β1 的水平与肺泡炎的分级对照相比较 ,各组 EGF水平变化与肺泡炎分级相关不显著 ,但 r值均为负值 .TGF- β1 水平升高与肺泡炎分级呈显著正相关 (P<0 .0 1) .结论 博莱霉素损伤早期肺泡 型细胞变性、坏死 ,抑制了 EGF自分泌的机制 ,诱导 TGF-β1 活性高表达是肺间质纤维化进程启动的重要因素之一 .

AIM Quantitative measurement of EGF, TGF β 1 in the alveolar lavage from pulmonary alveolitis (PAL) of the mouse mAel and comparative analysis of pathological grading of simultaneous pulmonary alveolitis with the ultrastructure changes of alveolar type II cell. METHODS PAL mouse mAels were established by single intratracheal injection of bleomycin A5 (BLM A 5). After 1, 3, 7 d,mouse mAels were operated on according to the divided groups and BAL was obtained. EGF and TGF β 1 quantitative expression of BAL was studied by adopting ELISA methA. The pulmonary tissues were obtained and the pathological change was demonstrated under routine microscope and the ultrastructure changes of alveolar type II cell were observed through an electronic microscope. RESULTS ELISA measurement of the experimental groups showed that EGF expressions of BAL of 1, 3 and 7 d groups were lower than those of normal groups ( P <0.01), but the TGF β 1 expressions increased while they did not make any distinct difference in contrast with the normal groups. Pathological examination discovered that the I rate PAL took a dominant position and with the development of the course it worsened into the Ⅱ and Ⅲ rate PAL gradually. The electronic microscope check up showed that the alveolar type Ⅱ cell in the experimental groups ended up in both degeneration and necrosis with the most striking distinction in 3, 7 d groups. The comparative analysis of EGF and TGF β 1 expression with the grading of PAL showed that the changes of EGF expression in each group were not clearly related with the grading of PAL, but r value proved negative. The increase of TGF β 1 expression had close association with the grading of PAL ( P <0.01). CONCLUSION Degeneration and necrosis of the alveolar type Ⅱ cell of pulmonary alveolitis in early Bleomycin induced pulmonary injuries may inhibit the autocrine of EGF while they induce the active high expression of TGF β 1, which might be one of the major factors in the initiation of pulmonary interstitial fibrosis.