重症急性胰腺炎大鼠胰腺全基因表达谱的变化  

Changes of genome expression profile in pancreas of rats with severe acute pancreatitis

作　　者：朱风尚[1] 朱国英[2] 黄东平[2] 沈晓莹[3] 杨长青[1] 郜恒骏[1,3] 

机构地区：[1]同济大学附属同济医院消化内科,上海200065 [2]上海市普陀区人民医院,上海200060 [3]生物芯片上海国家工程研究中心,上海201203

出　　处：《同济大学学报（医学版）》2013年第2期11-16,21,共7页Journal of Tongji University(Medical Science)

基　　金：上海市普陀区科委科研基金(PTKW08-C03)

摘　　要：目的观察牛磺胆酸钠诱导的重症急性胰腺炎(severe acute pancreatitis,SAP)大鼠胰腺基因表达谱的变化。方法 40只SD大鼠随机分为假手术组和SAP模型组,每组20只。经胰胆管逆行注射4%牛磺胆酸钠复制SAP模型,假手术组注射生理盐水,造模48 h后处死动物。检测血清淀粉酶和C-反应蛋白(C-reactive protein,CRP)水平;H-E染色观察胰腺和肺组织病理变化;Illumiina大鼠全基因组表达谱基因芯片分析胰腺表达谱变化:实时反转录-多聚酶链反应(Real-Time reverse transcription PCR,RT-PCR)验证部分基因(F11r、Cdh1)。结果 SAP模型组血清淀粉酶、CRP明显高于假手术组[(7 892±1 776.0)vs(1 296±326.2)U·L^(-1),P<0.01:(106.5±19.9)vs(61.7±15.9)μg·ml^(-1),P<0.01)];Schmidt胰腺病理半定量积分法显示,SAP组胰腺坏死、出血、炎性细胞浸润、水肿指数等较假手术组明显(均P<0.01)。与假手术组相比,胰腺组织表达谱28个基因表达明显变化,其中下调5个,上调23个。基因功能分析显示其与细胞黏附分子通路、钙钾离子通道、促分裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路、脂肪酸代谢等密切相关。RT-PCR对涉及细胞黏附的F11 r、Cdh1基因的验证证实了芯片结果。结论牛磺胆酸钠诱导的SAP大鼠基因表达谱改变涉及到细胞黏附、钙钾离子通道、MAPK信号通路和脂肪酸代谢。Objective To investigate the changes of genome expression profiles of pancreas in rats with severe acute pancreatifis （SAP）. Methods Forty Sprague-Dawley rats were randomly divided into sham control group （n = 20） and SAP group （n = 20 ）. SAP was induced by retrograded injection of 4% sodium taurocholate into the pancreatic duct of rats. After 48 h, the two group animals weresacrificed. Serum amylases, C-reactive protein （CRP）, pathological changes in pancrea and lung tissue were evaluated. Changes in pancreatic genome profile were examined with Rat Illumina microarry. Real-time reverse transcription PCR （RT-PCR） was adopted to validate the part of genes from microarray （Fllr, Cdhl ）. Results Serum levels of amylase, CRP in SAP group were significantly higher than those in the sham control group[ （7 892 ± 776. 0 ） vs （1 296± 326.2） U·L-1,P〈0.01; （106.5 ±19.9） vs （61.7±15.9）μg·ml-1, P〈0.01]. Schmidt semi- quantitative integration showed necrosis, hemorrhage, inflammatory cell infiltration, edema index in SAP group were significantly increased compared with the control group （ all P 〈 0.01 ）. Compared with the control group, the expressions of 28 genes were significantly changed included 5 down- regulated and 23 up-regulated. Gene function analysis showed that these genes were closely related to cell adhesion, calcium potassium channels, mitogen-activated protein kinase （MAPK） signaling pathway and fatty acid metabolism. The mRNA expressions of F11 r and Cdhl were validated by RT- PCR. Conclusion The gene expression profiles in pancreas are significantly changed in SAP rats induced by sodium taurocholate, and the mechanisms may involve in cell adhesion, calcium potassium channels, MAPK signaling pathway and fatty acid metabolism.

关 键 词：重症急性胰腺炎 基因芯片 表达谱 实时反转录-多聚酶链反应 

分 类 号：R576[医药卫生—消化系统]