微小RNA在大鼠慢性胰腺炎与正常胰腺组织中的表达差异

Differential expression of microRNA in the pancreatic tissue of rats with chronic pancreatitis and normal pancreatic tissues

目的 比较大鼠慢性胰腺炎（CP）胰腺组织与正常胰腺组织微小RNA （miRNA）表达谱的差异,探讨CP发病中潜在的关键调节作用的miRNA及其靶基因功能.方法 将16只SD大鼠随机分为实验组和对照组,分别尾部静脉注射二氯二丁基酯和无菌生理盐水建立模型,8周后检测血清淀粉酶及胰腺组织病理变化.检测分析胰腺组织miRNA表达谱差异,对差异表达的miRNA进行靶基因预测、Gene Ontology（GO）分析和信号通路分析.结果 实验组与对照组血清淀粉酶、病理组织学评分差异有统计学意义（P＜0.05）;两组miRNA表达谱差异明显,与对照组胰腺组织比较,实验组胰腺组织中上调miRNA共49个,下调miRNA共37个（变化倍数＞2.0,P＜0.05）,上调的部分miRNA参与胰腺组织的纤维化和细胞的凋亡.在差异表达miRNA中有24个（占27.91％）可以找到相应的靶基因,GO分析结果表明靶基因在细胞物质代谢、增殖周期、信号传导、胞外结构活动、细胞器合成等过程中起重要调节作用;信号通路分析表明基因在代谢通路、丝裂原活化蛋白激酶（MAPK）信号通路、癌症通路和Hedgehog信号通路等富集有显著变化.结论 慢性胰腺炎大鼠胰腺组织与正常大鼠胰腺组织中miRNA表达谱差异有统计学意义,miRNA通过调节靶基因的表达参与调控代谢通路、MAPK信号通路、癌症通路和Hedgehog信号通路等,在胰腺实质纤维化的进展和癌变中起重要调节作用.

Objective By comparing differences of microRNA （miRNA） expression profiles in chronic pancreatitis （CP） pancreatic tissue and normal pancreatic tissue of rats,to study the regulation function and protein-coding of miRNA in the fibrosis of CP organization and the biological function of the target gene.Methods Sixteen SD rats were divided into experimental and control groups randomly.Dichlorobis-butyl ester was injected via the tail vein in experimental group,and normal saline was given in control group.Serum amylase and pathological changes of pancreatic tissues after 8 weeks were observed.The differentially expressed miRNA profiles between CP and normal pancreatic tissues were analyzed by microarrays.The target gene was predicted,and the biological function （gene ontology,pathway analysis） of the target gene was investigated.Results The results showed that there was significant difference in serum amylase and histological score,and the expression levels of miRNA between two groups.As compared with control group,49 miRNAs were up-regulated,and 37 miRNAs were down-regulated （fold change 〉 2.0,P 〈 0.05） in experimental group.The up-regulated miRNAs were significantly related to the fibrosis and apoptosis of pancreatic tissues.Twenty-four miRNAs had their target gene.GO analysis showed that target genes played an important role in biological regulatory function.Pathway analysis revealed the pathways in mitogen-activated protein kinase （MAPK）,and carcinoma signaling pathways etc.significantly changed in the CP tissues as compared with normal pancreatic tissues （P 〈 0.05）.Conclusion It was suggested miRNA expression profiles showed significant difference between CP and normal pancreatic tissues.MiRNA regulated MAPK,Hedgehog and carcinoma signaling pathways by regulating the expression of target genes,and played an important regulatory role in the fibrosis progress and canceration.