大鼠胰腺癌和非癌胰腺组织DNA损伤修复蛋白表达及意义  

Expression of Repair Proteins of DNA Damage and Their Significances in Pancreatic Cancer and Non-cancerous Pancreatic Tissues of Sprague-Dawely (SD) Rats.

作　　者：杨竹林[1] 李清龙[1] 邓星辉[1] 杨乐平[1] 刘洁琼[1] 苗雄鹰[1] 

机构地区：[1]中南大学湘雅二医院肝胆疾病研究室,长沙410011

出　　处：《医学研究杂志》2009年第2期59-62,F0003,共5页Journal of Medical Research

摘　　要：目的建立SD(sprague-dawely)大鼠胰腺癌模型,研究胰腺癌发生过程中DNA损伤修复蛋白(MGMT,ERCC1,hMSH2,hMLH1)表达水平及其意义。方法将二甲基苯荓蒽(dimethylbenzanthracene,DMBA)直接置入胰腺实质内(A组+B组),B组每周腹腔注射曲古霉素A(trichostatin,TSA)1μg,A组和B组鼠于3～5个月内处死,对照组(C组)于第5个月处死;肉眼检查及HE染色观察胰腺癌发生情况,MGMT、ERCC1、hMSH2和hMLH1染色方法均为EnVisionTM免疫组化法。结果(1)A组3～5个月癌发生率为48.7%(18/37),17例为胰腺导管腺癌,1例为纤维肉瘤;B组3～5个月癌发生率为33.3%(12/36),11例为胰腺导管腺癌,1例为纤维肉瘤;A组胰腺肿瘤最大径均值大于B组(P<0.05);C组胰腺及A组、B组胰腺外主要脏器均无明显病理改变。(2)A组+B组胰腺导管腺癌组织MGMT、ERCC1、hMSH2和hMLH1表达阳性率明显低于A组+B组非癌胰腺组织(P<0.01或P<0.05),A组胰腺导管腺癌MGMT、ERCC1、hMSH2和hMLH1表达阳性率与A组非癌胰腺组织比较无明显差异(P>0.05),B组胰腺导管腺癌MGMT、ERCC1、hMSH2和hMLH1表达阳性率均较明显低于B组非癌胰腺组织(P≤0.05);C组胰腺组织4种修复蛋白均阳性表达;A组或B组非癌胰腺组织MGMT、ERCC1、hMSH2和hMLH1阴性表达者胰腺导管上皮均呈轻至重度不典型增生。结论较大剂量DMBA置入胰实质内可在短期内获得较高的胰腺癌发生率,TSA能干预胰腺癌的发生和生长;在DMBA诱导胰腺癌发生发展过程中DNA损伤修复蛋白失活起较重要作用。Objective To establish a model of pancreatic cancer induced by dimethylbenzantracene （DMBA） in SD rats, and to detect the expressive levels of repair proteins of DNA damage（ MGMT, ERCC1 , hMSH2 and hMLH1 ） and their effect on carcinogenesis of rat pancreas. Methods DMBA was directly implanted into the parenchyma of pancreas in rats （group A ＋ group B）. The rats of group B were treated with 1 ml TSA saline solution （1μg/ml） via ip weekly. The carcinogenesis of rats executed within 3 - 5months in group A and group B was observed by macrography and under microscopy. Meanwhile, the rats in the control group （group C） were executed in 5 months. The EnVision immunohistochemistry was used for assaying the expressive levels of MGMT, ERCC1, hMSH2 and hMLH1 in conventional paraffin - embedded sections from above pancreatic specimens. Results （ 1 ） The incidence of pancreatic cancer in group A within 3 -5 months was 48.7% （18/37） , including 17 cases of pancreatic ductal adenocarcinoma and 1 case of fibrosarcoma. The incidence of pancreatic cancer in group B was 33.3 % （12/36） , including 11 cases of pancreatic ductal adenocarcinoma and 1 cases of fibro sarcoma. The maximal diameter of tumor mass in group A was larger than that in group B （ P 〈 0.05 ）. No pathological changes were found in pancreas of group C and other main organs of group A and group B. （2） The positive rates of MGMT, ERCC1 , hMSH2 and hM- LH1 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 ）. No statistial differences were fnund among the expression rates of MGMT, ERCC1 , hMSH2 and hMLH1 in ductal adenocarcinoma and non - cancerous pancreatic tissues of group A （ P 〉 0.05 ）. The positive rates of MGMT, ERCC1 , hMSH2 and hMLHl were significantly lower in ductal adenocarcinoma of group B than those in non - cancerous pancreatic tissues of group B （ P〈0.05 ）. Pancreas of group

关 键 词：胰腺肿瘤 Sprague—Dawely大鼠 动物模型 DNA修复蛋白类 

分 类 号：R394[医药卫生—医学遗传学] R576[医药卫生—基础医学]