CAJ | 학술논문

目的探讨放射性肺损伤过程中吡啡尼酮对抗肺成纤维细胞(Fb)向肌成纤维细胞(MFb)转化的作用.方法将Wistar大鼠随机分为正常对照组、单纯照射组和照射+给药组,照射前2 d开始灌胃给予吡啡尼酮,用20 Gy~(60)Coγ射线进行全胸照射,于照射后2周应用图像分析测定肺组织放射性炎性反应范围的面密度;计算肺组织湿/干重比;免疫组化检测肺组织成纤维细胞a-平滑肌肌动蛋白(a-SMA)表达.应用免疫细胞化学和四甲基偶氮唑盐(MTT)比色法分别检测人肺成纤维细胞(HLF)表达TGF-β_1和细胞异常增生的程度.结果和单纯照射组相比,照射+给药组大鼠肺组织炎性病变区面密度、湿/干重比和a-SMA含量较照射组分别减少14.0%、3.82%和52.8%.吡啡尼酮可抑制照射促进HLF表达TGF-β_1和细胞增牛的作用,且此种抑制作用和给药剂量呈明显的依赖关系.结论吡啡尼酮对放射性肺损伤早期的间质性肺炎具有明显的对抗作用,并且可显著抑制肺Fb异常增生、TG-β_1表达和向肌成纤维细胞方向转化,有利于放射性肺纤维化的有效防治.
목적 탐토방사성폐손상과정중필배니동대항폐성섬유세포(Fb)향기성섬유세포(MFb)전화적작용.방법 장Wistar대서수궤분위정상대조조、단순조사조화조사+급약조,조사전2 d개시관위급여필배니동,용20 Gy~(60)Coγ사선진행전흉조사,우조사후2주응용도상분석측정폐조직방사성염성반응범위적면밀도;계산폐조직습/간중비;면역조화검측폐조직성섬유세포a-평활기기동단백(a-SMA)표체.응용면역세포화학화사갑기우담서염(MTT)비색법분별검측인폐성섬유세포(HLF)표체TGF-β_1화세포이상증생적정도.결과 화단순조사조상비,조사+급약조대서폐조직염성병변구면밀도、습/간중비화a-SMA함량교조사조분별감소14.0%、3.82%화52.8%.필배니동가억제조사촉진HLF표체TGF-β_1화세포증우적작용,차차충억제작용화급약제량정명현적의뢰관계.결론 필배니동대방사성폐손상조기적간질성폐염구유명현적대항작용,병차가현저억제폐Fb이상증생、TG-β_1표체화향기성섬유세포방향전화,유리우방사성폐섬유화적유효방치.
Objective To explore the effeets of pirfenidone antagonizing pulmonary fibroblasts (Fb) transformation towards myofibroblasts (MFb) during the course of radiational pulmonary mjury.Methods Wistar rats were randomly assigned into three groups:normal control group,radiation group and radiation and administration group.The rats were given with pirfenidone by intragastric administration 2 davs before radiation.The whole breasts of rats were irradiated by~(60)Co γ-rays at a dose of 20 Gy and 2 weeks after radiation area density of pulmonary radiational inflammation was determined by image analysis.The ralio of Dulmonary humid weight and dry weight was calculated.a-smooth muscle aetin (a-SMA) expression of pulmonary fibroblasts was examined by immunohistochemistry. Human lung fibroblasts (HLF) abnormal proliferation and TGF-β_1 expression were respectively detected by MTT colorimetric method and immunocytochemical stain.Results Compared with radiation group,the area density of pulmonary inflammatory pathological changes,the ratio of pulmonary humid weight and dry weight and pulmonary a-SMA content in rats of radiation and administration group were reduced by 14.0%,3.82% and 52.8%,respectively.Pirfenidone could suppress radiation-enhanced HLF proliferation and TGF-β_1 exDression in a dose-dependent manner. Conclusions Pirfenidone can antagonize the induction of interstitiai Dneumonia in the earlier period of radiational pulmonary injury evidently,and it can significantly suppress HLF abnormal proliferation,TGF-β_1 expression and transformation towards MFb,which help for preventing and curing radiational pulmonary fibrosis effectively.