特发性肺纤维化和特发性非特异性间质性肺炎中细胞因子的表达及分析
특발성폐섬유화화특발성비특이성간질성폐염중세포인자적표체급분석
The expressions and meanings of BMP-7 and TGF-β in idiopathic pulmonary fibrosis and idiopathic nonspecific interstitial pneumonia
  • 万方数据
    中华结核和呼吸杂志 중화결핵화호흡잡지
    Chinese Journal of Tuberculosis and Respiratory Diseases
    2014年 9期 664-670 ,共7页

    顾盼%罗本芳%易祥华%朱海龙%李帅%宇小婷%韩非%张素霞%朱旭友

    고반%라본방%역상화%주해룡%리수%우소정%한비%장소하%주욱우

    肺疾病,间质性%骨形成蛋白家族%基因芯片%免疫组织化学 肺疾病,間質性%骨形成蛋白傢族%基因芯片%免疫組織化學
    폐질병,간질성%골형성단백가족%기인심편%면역조직화학
    Pulmonary diseases,interstitial%Bone morphogenetic proteins%Gene microarray%Immunohistochemistry
    目的 探讨细胞因子在特发性肺纤维化(IPF)和特发性非特异性间质性肺炎(INSIP)患者中的表达状况,分析其中骨形成蛋白-7(BMP-7)和转化生长因子-β(TGF-β)的表达及意义.方法 选择经临床-影像-病理诊断的特发性间质性肺炎(IIP)47例,其中男27例,女20例,IPF 25例(IPF组),INSIP 22例(INSIP组,包括富于细胞型6例,纤维化型16例),正常肺组织作为对照.使用新鲜组织制作基因芯片,采用Oligo GEArray基因芯片技术检测114种细胞因子在各组表达状况.使用石蜡包块制作组织芯片,采用免疫组织化学EnVision法检测BMP-7和TGF-β蛋白在两组肺病灶组织中的表达.对两组患者进行5 ～10年的随访,用Kaplan-Meier法估计生存曲线.结果 基因芯片检测结果显示,与正常肺组织相比,两组在转化生长因子家族、白介素家族和肿瘤坏死因子家族总体表现为上调,而骨形成蛋白家族除BMP-5、BMP-8B、BMP-15外,其他成员表现为下调;组织芯片免疫组织化学结果显示,与正常肺组织相比,BMP-7表达在IPF组和INSIP组均下降(t=27.618,-12.404,均P＜0.001),IPF组低于INSIP组(t=5.387,P＜0.05),INSIP组富于细胞型表达高于纤维化型(t=-5.341,P＜0.001);TGF-β表达在IPF组和INSIP组中均明显高于对照组(t=23.393,-13.445,均P＜0.001),并且与BMP-7表达呈负相关(r=-0.771,-0.729,均P＜0.001).临床随访:IPF组与INSIP组在稳定(好转)、进展、死亡例数分别为0、2、23例和15、3、4例,2组间比较差异有统计学意义(均P＜0.01).BMP-7表达较高组与表达较低组中位生存时间分别为110.8和66.4个月(IPF组,t=-2.686,P=0.014＜0.05)和146.4及74.9个月(INSIP组,t=-3.037,P=0.007＜0.01).结论 细胞因子在IPF和INSIP患者体内有不同的表达谱.与高表达的TGF-β不同,BMP-7的表达受到抑制,是提示患者纤维化程度和不良预后的一个有用的标志物,有望成为研究IIP发生机制和预后潜在有用的基因靶点.
    목적 탐토세포인자재특발성폐섬유화(IPF)화특발성비특이성간질성폐염(INSIP)환자중적표체상황,분석기중골형성단백-7(BMP-7)화전화생장인자-β(TGF-β)적표체급의의.방법 선택경림상-영상-병리진단적특발성간질성폐염(IIP)47례,기중남27례,녀20례,IPF 25례(IPF조),INSIP 22례(INSIP조,포괄부우세포형6례,섬유화형16례),정상폐조직작위대조.사용신선조직제작기인심편,채용Oligo GEArray기인심편기술검측114충세포인자재각조표체상황.사용석사포괴제작조직심편,채용면역조직화학EnVision법검측BMP-7화TGF-β단백재량조폐병조조직중적표체.대량조환자진행5 ～10년적수방,용Kaplan-Meier법고계생존곡선.결과 기인심편검측결과현시,여정상폐조직상비,량조재전화생장인자가족、백개소가족화종류배사인자가족총체표현위상조,이골형성단백가족제BMP-5、BMP-8B、BMP-15외,기타성원표현위하조;조직심편면역조직화학결과현시,여정상폐조직상비,BMP-7표체재IPF조화INSIP조균하강(t=27.618,-12.404,균P＜0.001),IPF조저우INSIP조(t=5.387,P＜0.05),INSIP조부우세포형표체고우섬유화형(t=-5.341,P＜0.001);TGF-β표체재IPF조화INSIP조중균명현고우대조조(t=23.393,-13.445,균P＜0.001),병차여BMP-7표체정부상관(r=-0.771,-0.729,균P＜0.001).림상수방:IPF조여INSIP조재은정(호전)、진전、사망례수분별위0、2、23례화15、3、4례,2조간비교차이유통계학의의(균P＜0.01).BMP-7표체교고조여표체교저조중위생존시간분별위110.8화66.4개월(IPF조,t=-2.686,P=0.014＜0.05)화146.4급74.9개월(INSIP조,t=-3.037,P=0.007＜0.01).결론 세포인자재IPF화INSIP환자체내유불동적표체보.여고표체적TGF-β불동,BMP-7적표체수도억제,시제시환자섬유화정도화불량예후적일개유용적표지물,유망성위연구IIP발생궤제화예후잠재유용적기인파점.
    Objective To investigate the expressions of cytokines in idiopathic pulmonary fibrosis (IPF) and in idiopathic nonspecific interstitial pneumonia (INSIP) ; To discuss expressions and meanings of bone morphogenetic protein 7 (BMP-7) and transforming growth factor beta (TGF-β) in IPF and IPF.Methods Selected 47 cases of idiopathic interstitial pneumonia (IIP),which were diagnosed by clinical-radiologic-pathologic (CRP),and classified into two groups which were group IPF (25 IPF) and group INSIP (22 INSIP,including 6 cellular pattern and 16 fibrosing pattern).The normal lung tissues were collected as the control group:The fresh tissues were made to detect more than 114 kinds of cytokines' expressions via Oligo GEArray gene microarray technology.Made a tissue microarray which applied EnVision immunohistochemistry technology to detect the expressions of BMP-7 and TGF-β in both kinds of IIPs.The two groups of patients were followed-up visited around 5 to 8 years and the survival curves were evaluated by Kaplan-Meier method.Results According to gene microarray results,these two groups were up-expression in TGF family,IL family and TNF family.Most of BMP members were down-expression,in comparison with the control group,except BMP-5,BMP-8B and BMP-15.As the tissue microarray results demonstrated,compared with normal lung tissues,BMP-7 expressed decreasingly in IPF and INSIP groups (t1 =27.618,P ＜ 0.001 ;t2 =-12.404,P ＜ 0.001).The expression of IPF were lower than INSIP (t =5.387,P ＜ 0.05) ; In INSIP group,patients of cellular pattern expressed BMP-7 more than fibrosing pattern' s (t =-5.341,P ＜ 0.001).There were dramatically increasing expressions of TGF-β in IPF and INSIP,when compared with the control group (t1 =23.393,P ＜0.001 ; t2 =-13.445,P ＜0.001) and it presented negative correlation with BMP-7 (group IPF:r =-0.771,P ＜ 0.001 ; group INSIP:r =-0.729,P ＜ 0.001).(3) Clinical follow-up data showed,the stability(improvement),deterioration and death rates of the group IPF and the group INSIP were,respectively,0 (0％),2 (8％),23 (92％) and 15 (68.1％),3 (13.6％),4 (18.2％).The results were statistically significant (all P ＜0.05).The median survival time of the part with higher BMP-7 expression and the part with relatively lower BMP-7 expression,in the group IPF,were 110.8 and 66.4 months (t =-2.686,P ＜0.05) ; In the group INSIP,were 146.4 and 74.9 months (t =-3.037,P ＜0.05).Conclusions Cellular cytokines presented different expression profiles in IPF and INSIP patients.Differently with highly activated TGF-β,BMP-7 was inhibited in IIP patients,which would remind the degree of fibrosis and prognosis of IIP.BMP-7 would be expected to be a novel target for IIP pathogenesis and prognostic research.
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