机构地区:[1]中南大学湘雅三医院病理科,湖南长沙410003 [2]中南大学湘雅二医院肝胆胰疾病研究室,湖南长沙410011
出 处:《第四军医大学学报》2009年第22期2595-2598,共4页Journal of the Fourth Military Medical University
摘 要:目的:建立SD大鼠胰腺癌模型,研究细胞连接调控蛋白(Claudin-1,Occludin,E-cad,Snail)在胰腺癌发生发展过程中的作用及其意义.方法:90只大鼠随机分为二甲基苯荓蒽(DMBA)组(A组,n=40),DMBA+曲古霉素A(TSA)组(B组,n=40)和空白对照组(C组,n=10只).将DMBA直接置入A,B组胰腺实质内建立胰腺癌模型,B组腹腔注射TSA,~5mo内处死并观察胰腺癌发生情况,C组于第5mo处死.采用En-VisionTM免疫组化法检测Claudin-1,Occludin,E-cad,Snail的表达.结果:A组3~5mo癌发生率为48.6%(18/37),5mo(60.0%)高于4mo组(40.0%)和3mo组(28.6%).B组3~5mo癌发生率为33.3%(12/36),5mo(40.0%)高于4mo组(30.0%)和3mo组(16.7%).A组发癌率高于B组.A组,B组胰腺导管癌分别为17例和11例,其余为纤维肉瘤;A组胰腺癌最大径均值大于B组(A组:0.5~1.0cm7例,1.0~2.0cm10例,>2.0cm1例;B组:0.5~1.0cm9例,1.0~2.0cm2例,>2.0cm1例,P<0.05);C组胰腺和A,B,C组胰腺外主要脏器均未见明显病理改变.A组+B组胰腺导管癌Clau-din-1,Occludin,E-cad表达阳性率明显低于A组+B组非癌胰腺组织(P<0.05或P<0.01),但Snail则相反(P<0.01);在胰腺导管腺癌中Claudin-1,Occludin,E-cad表达均相互呈一致性(P<0.05或P<0.01),但三者均与Snail表达呈明显不一致性(P<0.05或P<0.01).结论:较大剂量DMBA置入胰实质内可在短期内获得较高的SD鼠胰腺癌发生率,TSA能抑制胰腺癌发生和生长;Claudin-1,Occludin,E-cad和Snail在DM-BA诱导SD大鼠胰腺癌发生中可能有重要作用.AIM:To establish a model of pancreatic cancer in Sprague-Dawely(SD)rats,and to detect the expression of regulated proteins in cell junctions(Claudin-1,Occludin,E-cad,Snail)and their significances on the carcinogenesis in rats pancreas.METHODS:Ninety rats were randomly divided into A(n=40),B(n=40)and C(n=10)groups.For group A and B,dimethylbenzathracene,(DMBA)was directly implanted into the parenchyma of rat pancreas to establish pancreatic cancer model.The rats of group B were treated with trichostatin A(TSA)via intraperitoneal weekly.The rats in group C served as the controls.The rats were executed within 3-5 months,and the carcinogenesis of the rats was observed by pathological methods.The EnvisionTMimmunohistochemistry for assaying the expressive levels of Claudin-1,Occludin,E-cad and Snail was used in conventional paraffin-embedded sections from above pancreatic specimens.RESULTS:The incidence of pancreatic cancer in group A within 3-5 months was 48.6%(18/37),28.6%(2/7)at 3 months,40.0%(4/10)at 4 months and 60.0%(12/20)at 5 months.And that in group B was 33.3%(12/36),16.7%(1/6),30.0%(3/10)and 40.0%(8/20),respectively.The prevalence rate in group A was higher than that of group B.Cases of pancreatic ductal adenocarcinoma in group A and B respectively were 17 and 11,and others were fibrosarcoma.The maximal diameter of tumor mass in group A were significantly larger than those in group B(group A:0.5-1.0 cm 7 cases,1.0-2.0 cm 10 cases,2.0 cm 1 case vs group B:0.5-1.0 cm 9 cases,1.0-2.0 cm 2 cases,2.0 cm 1 case,P〈0.05).No pathological changes were found in pancreas of group C and other main organs of group A,B and C.The positive rates of Claudin-1,Occludin and E-cad were significantly lower in ductal adenocarcinoma of group A + group B than those in non-cancerous pancreatic tissues of group A + group B(P〈0.05 or P〈0.01);but Snail was opposite(P〈0.01).The consistencies were found among the expressive levels of clanudin-1,O
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