【摘要】：背景：變應(yīng)性鼻炎是耳鼻咽喉頭頸外科中的常見疾病。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)站對相關(guān)microRNA靶點進(jìn)行預(yù)測,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)病過程中對Thl/Th2細(xì)胞失衡的影響。利用雙熒光素酶的方法驗證網(wǎng)站預(yù)測的GATA3是否確實為mir-466a-3p的靶基因。利用mir-466a-3p模擬物在小鼠脾單個核細(xì)胞過表達(dá)mir-466a-3p,檢測GATA3蛋白的表達(dá)變化。另外,通過構(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。雙熒光素酶報告系統(tǒng)證實GATA3為mir-466a-3p的靶基因,與網(wǎng)站預(yù)測的結(jié)果相符。同時,體外實驗發(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)實驗也發(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作為分子靶點的變應(yīng)性鼻炎的治療奠定理論依據(jù)和實驗參考,具有一定的理論與實踐意義。
[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)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R765.21

【共引文獻(xiàn)】

相關(guān)期刊論文 前10條

1 黃學(xué)勤;程學(xué)仕;王俊芳;楊洋;;粉塵螨滴劑治療變應(yīng)性鼻炎的臨床療效及安全性觀察[J];安徽醫(yī)藥;2010年06期

2 曾小芳;;免疫脫敏治療過敏性鼻炎的護(hù)理[J];當(dāng)代護(hù)士(學(xué)術(shù)版);2010年09期

3 岳文江;倪宏亮;黃偉;;320例手術(shù)治療變應(yīng)性鼻炎療效觀察[J];中國醫(yī)藥導(dǎo)刊;2012年03期

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5 楊東寶;梁小軍;李麗萍;;變應(yīng)性鼻炎合并鼻腔解剖結(jié)構(gòu)異常50例[J];第三軍醫(yī)大學(xué)學(xué)報;2012年14期

6 索利敏;趙長青;安云芳;韓穎;賈建生;王嬡;師新宇;;太原市迎澤區(qū)10～11歲兒童變應(yīng)性鼻炎自報患病率調(diào)查分析[J];中國耳鼻咽喉頭頸外科;2009年04期

7 孟娟;張虹婷;劉世喜;;鼻用激素與孟魯司特鈉治療中重度持續(xù)性變應(yīng)性鼻炎的隨機(jī)對照研究[J];中國耳鼻咽喉頭頸外科;2010年11期

8 黃雪琨;陳玉蓮;張革化;楊欽泰;;廣州地區(qū)1376例變應(yīng)性鼻炎常見吸入性變應(yīng)原分析[J];中國耳鼻咽喉頭頸外科;2011年07期

9 王e，

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