【摘要】：背景：變應(yīng)性鼻炎是耳鼻咽喉頭頸外科中的常見(jiàn)疾病。它是由IgE介導(dǎo)的免疫反應(yīng),以Th2相關(guān)的細(xì)胞因子分泌增加,鼻黏膜嗜酸性粒細(xì)胞和鼻腔分泌物增多為特征的變態(tài)反應(yīng)性疾病。 方法：本研究通過(guò)microRNA芯片技術(shù)篩選出變應(yīng)性鼻炎小鼠鼻黏膜中表達(dá)發(fā)生顯著性改變的microRNA.利用網(wǎng)站對(duì)相關(guān)microRNA靶點(diǎn)進(jìn)行預(yù)測(cè),結(jié)合當(dāng)前文獻(xiàn)研究的進(jìn)展著眼于在變應(yīng)性小鼠鼻黏膜中表達(dá)下降的mir-466a-3p,探討其在小鼠變應(yīng)性鼻炎發(fā)病過(guò)程中對(duì)Thl/Th2細(xì)胞失衡的影響。利用雙熒光素酶的方法驗(yàn)證網(wǎng)站預(yù)測(cè)的GATA3是否確實(shí)為mir-466a-3p的靶基因。利用mir-466a-3p模擬物在小鼠脾單個(gè)核細(xì)胞過(guò)表達(dá)mir-466a-3p,檢測(cè)GATA3蛋白的表達(dá)變化。另外,通過(guò)構(gòu)建mir-466a-3p的模擬物,尾靜脈注射變應(yīng)性鼻炎小鼠,檢測(cè)小鼠變應(yīng)性鼻炎相關(guān)指標(biāo)的改變及GATA3蛋白的表達(dá)變化。 結(jié)果：MicroRNA芯片結(jié)果發(fā)現(xiàn),在變應(yīng)性鼻炎小鼠鼻黏膜中部分microRNAs表達(dá)與正常小鼠差異顯著。雙熒光素酶報(bào)告系統(tǒng)證實(shí)GATA3為mir-466a-3p的靶基因,與網(wǎng)站預(yù)測(cè)的結(jié)果相符。同時(shí),體外實(shí)驗(yàn)發(fā)現(xiàn)mir-466a-3p的表達(dá)增加可以抑制GATA3蛋白的表達(dá)；體內(nèi)實(shí)驗(yàn)也發(fā)現(xiàn)給予變應(yīng)性鼻炎小鼠mir-466a-3p模擬物后使該microRNA表達(dá)趨于正常,可以使GATA3蛋白的表達(dá)水平較變應(yīng)性鼻炎組下調(diào),從而起到調(diào)節(jié)Thl/Th2細(xì)胞的平衡,緩解變應(yīng)性鼻炎癥狀,達(dá)到治療變應(yīng)性鼻炎的作用。 結(jié)論：本研究探究了microRNAs在變應(yīng)性鼻炎發(fā)病中的作用,為其發(fā)病機(jī)制的研究提供全新的視角,為以mir-466a-3p作為分子靶點(diǎn)的變應(yīng)性鼻炎的治療奠定理論依據(jù)和實(shí)驗(yàn)參考,具有一定的理論與實(shí)踐意義。
[Abstract]:Background: allergic rhinitis is a common disease in otolaryngology. It is an allergic disease mediated by IgE, characterized by increased secretion of cytokines associated with Th2, increased eosinophil and nasal secretion in nasal mucosa. Methods: in this study, microRNA microarray was used to screen microRNA. in nasal mucosa of allergic rhinitis mice. The site was used to predict the relevant microRNA targets, and the current research progress was focused on exploring the effect of mir-466a-3p, on the imbalance of Thl/Th2 cells in allergic rhinitis during the pathogenesis of allergic rhinitis in mice with decreased expression of mir-466a-3p, in the nasal mucosa of allergic mice. Double luciferase method was used to verify whether the GATA3 predicted by the website was indeed the target gene of mir-466a-3p. Mir-466a-3p mimics were used to detect the expression of GATA3 protein in murine splenic mononuclear cells by overexpression of mir-466a-3p,. In addition, by constructing the mimic of mir-466a-3p and injecting mice with allergic rhinitis via caudal vein, the changes of related indexes and the expression of GATA3 protein in allergic rhinitis mice were detected. Results the expression of microRNAs in nasal mucosa of allergic rhinitis mice was significantly different from that of normal mice. Double luciferase reporting system confirmed that GATA3 was the target gene of mir-466a-3p, which was consistent with the results predicted by the website. At the same time, it was found in vitro that the increased expression of mir-466a-3p could inhibit the expression of GATA3 protein, and the in vivo experiment also found that the expression of microRNA tended to normal after giving mir-466a-3p mimics of allergic rhinitis mice. The expression level of GATA3 protein was lower than that of allergic rhinitis group, which could regulate the balance of Thl/Th2 cells, alleviate the symptoms of allergic rhinitis, and achieve the effect of treating allergic rhinitis. Conclusion: this study explored the role of microRNAs in the pathogenesis of allergic rhinitis, provided a new perspective for the study of its pathogenesis, and laid a theoretical and experimental reference for the treatment of allergic rhinitis with mir-466a-3p as a molecular target. It has certain theoretical and practical significance.
【學(xué)位授予單位】：武漢大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R765.21

【共引文獻(xiàn)】

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