本文選題：基因芯片 + 鼻息肉　； 參考：《山東大學(xué)》2010年碩士論文

【摘要】： 研究背景鼻息肉是耳鼻喉科常見(jiàn)病之一,好發(fā)于鼻竇及中鼻道,臨床表現(xiàn)為局部鼻腔粘膜水腫及半透明隆起,治療以手術(shù)切除為主,易復(fù)發(fā)。其病理學(xué)特點(diǎn)包括上皮杯狀細(xì)胞增生、基底膜增厚、大量白細(xì)胞特別是嗜酸粒細(xì)胞浸潤(rùn)等。鼻息肉發(fā)病機(jī)理至今尚未完全明確,現(xiàn)有的研究認(rèn)為其與炎癥,感染及變態(tài)反應(yīng)等關(guān)系密切。國(guó)內(nèi)外學(xué)者通過(guò)實(shí)驗(yàn)證實(shí)了和上述因素密切相關(guān)的效應(yīng)細(xì)胞及細(xì)胞因子在鼻息肉中廣泛存在。國(guó)外最新的研究認(rèn)為鼻息肉的發(fā)生發(fā)展受到許多特異性基因的調(diào)控,而國(guó)內(nèi)現(xiàn)有的實(shí)驗(yàn)研究大多停留在傳統(tǒng)的技術(shù)層面上,很少?gòu)幕蛩窖芯科浒l(fā)病機(jī)理�；蛐酒鳛橐环N新型的實(shí)驗(yàn)技術(shù)已經(jīng)在其他研究領(lǐng)域取得了突出穩(wěn)定的實(shí)驗(yàn)成果。在基因水平的實(shí)驗(yàn)研究中,基因芯片技術(shù)已成為目前最有效的研究手段之一 研究目的通過(guò)應(yīng)用寡聚核苷酸基因表達(dá)譜芯片(GeneChip)研究鼻息肉組織中基因表達(dá)譜的變化,在基因水平上探討鼻息肉發(fā)病的分子生物學(xué)機(jī)制。 研究方法應(yīng)用HG-U133A2. 0(Affymetrix公司)基因芯片檢測(cè)分析5例單純鼻息肉組織,4例合并哮喘鼻息肉組織及5例正常鼻黏膜組織。鼻息肉及哮喘診斷分別依據(jù)病理檢查結(jié)果和肺功能檢查結(jié)果。應(yīng)用RMA標(biāo)準(zhǔn)化軟件將基因芯片的原始掃描數(shù)據(jù)進(jìn)行質(zhì)量控制后行數(shù)據(jù)標(biāo)準(zhǔn)化,應(yīng)用SAM統(tǒng)計(jì)分析軟件進(jìn)行統(tǒng)計(jì)學(xué)分析,篩選出有意義的目的基因后應(yīng)用IPA軟件對(duì)其進(jìn)行繪圖,分析典型差異表達(dá)基因及其信號(hào)通路變化。 實(shí)驗(yàn)結(jié)果SAM統(tǒng)計(jì)分析軟件分析顯示：?jiǎn)渭儽窍⑷饨M及鼻息肉合并哮喘組之間基因表達(dá)的差異無(wú)統(tǒng)計(jì)學(xué)意義,鼻息肉病例組(單純鼻息肉組+鼻息肉合并哮喘組)與正常對(duì)照組之間基因差異有統(tǒng)計(jì)學(xué)意義。應(yīng)用SAM統(tǒng)計(jì)軟件(False Discovery Rate, FDR值=5.8)篩選出鼻息肉組對(duì)照正常鼻黏膜組差異表達(dá)基因共2122個(gè),其中下調(diào)基因871個(gè),上調(diào)基因1251個(gè)。下調(diào)基因中,Fold Change≥0.5的基因?yàn)?33個(gè),上調(diào)基因中,Fold Change≥2為486個(gè)。應(yīng)用IPA軟件分析挑選出的目的基因發(fā)現(xiàn)：TGFβ信號(hào)傳導(dǎo)系統(tǒng)、花生四烯酸系統(tǒng)及補(bǔ)體系統(tǒng)信號(hào)傳導(dǎo)通路相關(guān)基因在鼻息肉組織中大多呈上調(diào)表達(dá)。 結(jié)論(1)TGFβ在鼻息肉中的表達(dá)明顯上調(diào),其信號(hào)通路中細(xì)胞因子(TGFβ1,TGFβ2,Smad2／3等)表達(dá)亦發(fā)生變化。此結(jié)果表明鼻息肉的形成有免疫因子的參與,局部嗜酸粒細(xì)胞浸潤(rùn)及組織結(jié)構(gòu)重塑亦參與鼻息肉發(fā)生。(2)鼻息肉中補(bǔ)體(C3、C4、C1q等)活性的增加,表明了炎性因子及炎性細(xì)胞代謝產(chǎn)物是鼻息肉形成的重要原因之一。(3)在鼻息肉組織的花生四烯酸信號(hào)通路中,白三烯和前列腺素E2傳導(dǎo)途徑中的基因表達(dá)明顯變化,表明了變態(tài)反應(yīng)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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