鼻息肉的基因表达谱研究及发病机理探讨

发布时间：2018-07-08 19:25

  本文选题：基因芯片 + 鼻息肉　； 参考：《山东大学》2010年硕士论文

【摘要】： 研究背景鼻息肉是耳鼻喉科常见病之一,好发于鼻窦及中鼻道,临床表现为局部鼻腔粘膜水肿及半透明隆起,治疗以手术切除为主,易复发。其病理学特点包括上皮杯状细胞增生、基底膜增厚、大量白细胞特别是嗜酸粒细胞浸润等。鼻息肉发病机理至今尚未完全明确,现有的研究认为其与炎症,感染及变态反应等关系密切。国内外学者通过实验证实了和上述因素密切相关的效应细胞及细胞因子在鼻息肉中广泛存在。国外最新的研究认为鼻息肉的发生发展受到许多特异性基因的调控,而国内现有的实验研究大多停留在传统的技术层面上,很少从基因水平研究其发病机理。基因芯片作为一种新型的实验技术已经在其他研究领域取得了突出稳定的实验成果。在基因水平的实验研究中,基因芯片技术已成为目前最有效的研究手段之一 研究目的通过应用寡聚核苷酸基因表达谱芯片(GeneChip)研究鼻息肉组织中基因表达谱的变化,在基因水平上探讨鼻息肉发病的分子生物学机制。 研究方法应用HG-U133A2. 0(Affymetrix公司)基因芯片检测分析5例单纯鼻息肉组织,4例合并哮喘鼻息肉组织及5例正常鼻黏膜组织。鼻息肉及哮喘诊断分别依据病理检查结果和肺功能检查结果。应用RMA标准化软件将基因芯片的原始扫描数据进行质量控制后行数据标准化,应用SAM统计分析软件进行统计学分析,筛选出有意义的目的基因后应用IPA软件对其进行绘图,分析典型差异表达基因及其信号通路变化。 实验结果SAM统计分析软件分析显示：单纯鼻息肉组及鼻息肉合并哮喘组之间基因表达的差异无统计学意义,鼻息肉病例组(单纯鼻息肉组+鼻息肉合并哮喘组)与正常对照组之间基因差异有统计学意义。应用SAM统计软件(False Discovery Rate, FDR值=5.8)筛选出鼻息肉组对照正常鼻黏膜组差异表达基因共2122个,其中下调基因871个,上调基因1251个。下调基因中,Fold Change≥0.5的基因为533个,上调基因中,Fold Change≥2为486个。应用IPA软件分析挑选出的目的基因发现：TGFβ信号传导系统、花生四烯酸系统及补体系统信号传导通路相关基因在鼻息肉组织中大多呈上调表达。 结论(1)TGFβ在鼻息肉中的表达明显上调,其信号通路中细胞因子(TGFβ1,TGFβ2,Smad2／3等)表达亦发生变化。此结果表明鼻息肉的形成有免疫因子的参与,局部嗜酸粒细胞浸润及组织结构重塑亦参与鼻息肉发生。(2)鼻息肉中补体(C3、C4、C1q等)活性的增加,表明了炎性因子及炎性细胞代谢产物是鼻息肉形成的重要原因之一。(3)在鼻息肉组织的花生四烯酸信号通路中,白三烯和前列腺素E2传导途径中的基因表达明显变化,表明了变态反应及炎性因子在鼻息肉形成中起重要作用。
[Abstract]:Background nasal polyp is one of the most common diseases in otolaryngology. It usually occurs in the nasal sinus and middle nasal canal. Its clinical manifestations are local nasal mucosal edema and semitransparent protuberance. Its pathological features include epithelial goblet cell proliferation, basement membrane thickening, leukocyte infiltration, especially eosinophil infiltration. Up to now, the pathogenesis of nasal polyps has not been completely clear, and the existing studies suggest that it is closely related to inflammation, infection and allergic reaction. Domestic and foreign scholars have confirmed that the effector cells and cytokines closely related to the above factors exist widely in nasal polyps. The latest studies abroad believe that the occurrence and development of nasal polyps are regulated by many specific genes, but most of the existing experimental studies stay on the traditional technical level, and rarely study the pathogenesis of nasal polyps at the gene level. As a new type of experimental technology, gene chip has obtained outstanding and stable experimental results in other research fields. In experimental studies at the gene level, Gene chip technology has become one of the most effective research methods objective to study the changes of gene expression profile in nasal polyp tissue by using gene chip of oligonucleotide gene expression profile (GeneChip). To explore the molecular biological mechanism of nasal polyps at the gene level. Methods HG-U133A2. 0 (Affymetrix) gene chip analysis was performed in 5 cases of simple nasal polyps, 4 cases of asthmatic nasal polyps and 5 cases of normal nasal mucosa. The diagnosis of nasal polyps and asthma were based on pathological examination and pulmonary function examination. RMA standardization software was used to standardize the original scanning data of gene chip after quality control, and SAM statistical analysis software was used to carry out statistical analysis. The meaningful target gene was selected and the IPA software was used to plot it. The changes of typical differentially expressed genes and their signaling pathways were analyzed. Results SAM statistical analysis software showed that there was no significant difference in gene expression between simple nasal polyp group and nasal polyp with asthma group. The gene difference between nasal polyp group (simple nasal polyp group with asthma group) and normal control group was statistically significant. A total of 2122 differentially expressed genes were screened by means of false Discovery Rate5.8 (FDR 5.8) in normal nasal mucosa, including 871 down-regulated genes and 1251 up-regulated genes. There were 533 genes with Fold change 鈮，

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