摘要
目的 急性胰腺炎是消化系统常见的急腹症,患病率高,治疗方法有限,发病机制复杂。本研究的目的是确定急性胰腺炎发病中可靠的差异表达基因和潜在的致病机制,丰富急性胰腺炎的研究,为未来在治疗上提供更多的参考价值和依据。方法 从GEO数据库获得高通量数据集GSE194331和GSE109227的全基因组表达谱,找出表达值高且存在共表达的差异表达基因,再对这些基因蛋白质-蛋白质相互作用网络构建,筛选出存在关联的50个基因,进一步对这些基因进行基因本体和KEGG通路富集分析。接下来,从中挑出一个目标基因NMI进行实验验证。首先,收取急性胰腺炎患者的血液样本验证NMI的激活。然后,用雨蛙素对野生小鼠造急性胰腺炎模型验证NMI的活化。最后,通过NMI基因敲除小鼠验证NF-κB信号通路。结果 从数据集中筛查出246个共表达的差异基因,其中50个基因在蛋白互作网中存在着关联性,基因富集分析表明这些基因主要参与了NF-κB、TLR和MAP多条信号传导通路。实验也验证了从中挑选出的NMI基因在急性胰腺炎患者和野生鼠的胰腺炎模型中激活,并且NMI基因敲除后,小鼠胰腺组织的NF-κB/p65的基础表达水平明显降低,磷酸化NF-κB/p65在NMI KO胰腺炎组小鼠中活化水平明显低于野生胰腺炎组。NMI KO胰腺炎组中胰腺腺泡的损伤程度比野生胰腺炎组低。结论 NMI可通过NF-κB信号通路促进急性胰腺炎的损伤过程。
Objective Acute pancreatitis is a common acute abdomen of the digestive system with high prevalence, limited treatment methods and complex pathogenesis. The aim of this study is to identify reliable differentially expressed genes and potential pathogenesis in the pathogenesis of acute pancreatitis, and to enrich the research on acute pancreatitis, so as to provide more reference value and basis for future treatment. Methods Genome-wide expression profiles of high-throughput datasets GSE194331 and GSE109227 were obtained from GEO database, and differentially expressed genes with high expression values and co-expression were identified. Then, the protein-protein interaction network of these genes was constructed, and 50 genes were screened out. The Gene Ontology and KEGG pathway enrichment analysis of these genes were carried out. Next, the target gene NMI was selected for experimental verification. Blood samples from acute pancreatitis patients were collected to detect NMI activation. The activation of NMI was verified by acute pancreatitis in wild mice with caerulein. NF-κB signaling pathway was verified by NMI knockout mice. ResultsA total of 246 co-expressed differentially expressed genes were identified from the data set, of which 50 genes were associated with each other in the protein-protein interaction network. Gene enrichment analysis showed that these genes were mainly involved in NF-κB, TLR and MAP signaling pathways. Experiments also confirmed that the selected NMI genes were activated in acute pancreatitis patients and wild mice models of pancreatitis. After NMI knockout(NMI KO), the basal expression level of NF-κB/p65 in pancreatic tissue of mice was significantly decreased, and the expression level of phosphorylated NF-κB/p65 in NMI KO pancreatitis group was significantly lower than that in wild type pancreatitis group. The pancreatic tissue injury in NMI KO pancreatitis group was lower than that in wild type pancreatitis group. Conclusion NMI can promote the process of acute pancreatitis injury
作者
吴浪
陈升鑫
张贯军
张大涯
陈德鑫
李明阳
WU Lang;ZHANG Guan-jun;ZHANG Da-ya;CHEN Sheng-xin;CHEN De-xin;LI Ming-yang(Chinese PLA Medical School,Beijing 100853,China;Department of Gastroenterology,the First Medical Center,Chinese PLA General Hospital,Beijing 100853,China)
出处
《现代消化及介入诊疗》
2022年第9期1141-1146,共6页
Modern Interventional Diagnosis and Treatment in Gastroenterology
