【摘要】：目的：探討乳鐵蛋白在變應(yīng)性鼻炎小鼠鼻腔中蛋白和基因表達(dá)水平及其和變應(yīng)性鼻炎的關(guān)系,研究小鼠鼻腔滴入重組人乳鐵蛋白對變應(yīng)性鼻炎的防治作用,并探討其可能的分子機制。 方法：采用卵清蛋白建立BALB/c小鼠變應(yīng)性鼻炎動物模型,用蘇木素-伊紅,高碘夫稀,肥大細(xì)胞染色方法分析鼻黏膜嗜酸性粒細(xì)胞,杯狀細(xì)胞和肥大細(xì)胞浸潤的情況。用熒光定量RT-PCR和酶聯(lián)免疫方法檢測小鼠鼻腔中T淋巴細(xì)胞亞群轉(zhuǎn)錄因子和細(xì)胞因子以及乳鐵蛋白基因和蛋白的表達(dá)水平。用Spearman分析鼻腔中的乳鐵蛋白表達(dá)水平和嗜酸性粒細(xì)胞的相關(guān)性。 結(jié)果：與正常小鼠相比,嗜酸性粒細(xì)胞,杯狀細(xì)胞和肥大細(xì)胞的數(shù)量,Th2、Th17、 Treg基因和蛋白表達(dá)水平在變應(yīng)性鼻炎小鼠鼻腔顯著增加(P0.01),但是在卵清蛋白激發(fā)前和激發(fā)后鼻腔給予重組人乳鐵蛋白后均顯著減少(P0.01)。Thl相關(guān)基因和蛋白表達(dá)水平在正常小鼠和模型小鼠之間無明顯差異,但是給予重組人乳鐵蛋白治療后明顯上調(diào)(P0.01)。與正常小鼠相比,內(nèi)源性乳鐵蛋白的基因和蛋白表達(dá)水平在變應(yīng)性鼻炎小鼠鼻腔顯著下調(diào)(P0.01),但是給予重組人乳鐵蛋白治療后明顯上調(diào)(P0.01)。Spearman相關(guān)分析顯示乳鐵蛋白表達(dá)水平和嗜酸性粒細(xì)胞數(shù)量成負(fù)向關(guān)系(r=-0.920,P0.01)。 結(jié)論：內(nèi)源性乳鐵蛋白在變應(yīng)性鼻炎小鼠鼻腔中表達(dá)下調(diào),該蛋白表達(dá)不足可能與變應(yīng)性鼻炎的發(fā)生和發(fā)展相關(guān)。外源性乳鐵蛋白抑制了小鼠變應(yīng)性鼻炎的炎癥,其機制可能與增強了內(nèi)源性乳鐵蛋白的表達(dá),促進了Thl細(xì)胞活性和抑制Th2以及Th17細(xì)胞反應(yīng)有關(guān)。該研究結(jié)果提示乳鐵蛋白在未來可能作為一種新的預(yù)防和治療變應(yīng)性鼻炎的制劑。
[Abstract]:Objective: to investigate the expression of lactoferrin in nasal cavity of allergic rhinitis mice and its relationship with allergic rhinitis, and to study the preventive and therapeutic effects of recombinant human lactoferrin on allergic rhinitis. The possible molecular mechanism was also discussed. Methods: the animal model of allergic rhinitis in BALB/c mice was established by ovalbumin. The infiltration of eosinophils goblet cells and mast cells in nasal mucosa was analyzed by hematoxylin-eosin hyperiodophore and mast cell staining. The expression levels of transcription factors, cytokines, lactoferrin genes and proteins in T lymphocyte subsets in nasal cavity of mice were detected by fluorescence quantitative RT-PCR and enzyme-linked immunosorbent assay (Elisa). The correlation between the expression of lactoferrin and eosinophil in nasal cavity was analyzed by Spearman. Results: the number of eosinophilic granulocytes, goblet cells and mast cells, and the expression of Th2,Th17, Treg gene and protein were significantly increased in allergic rhinitis mice compared with normal mice (P0.01). However, the expression of recombinant human lactoferrin in nasal cavity before and after ovalbumin stimulation was significantly decreased (P0.01). Thl related gene and protein expression levels were not significantly different between normal mice and model mice. But after treatment with recombinant human lactoferrin, it was significantly up-regulated (P0.01). Compared with normal mice, the expression of endogenous lactoferrin gene and protein was significantly decreased in allergic rhinitis mice (P0.01). However, the expression of lactoferrin was significantly up-regulated after treatment with recombinant human lactoferrin (P0.01). Spearman correlation analysis showed that the expression of lactoferrin was negatively correlated with the number of eosinophils (r-0.920, P0.01). Conclusion: the expression of endogenous lactoferrin is down-regulated in the nasal cavity of allergic rhinitis mice, which may be related to the occurrence and development of allergic rhinitis. Exogenous lactoferrin inhibited the inflammation of allergic rhinitis in mice. The mechanism may be related to the enhancement of endogenous lactoferrin expression, the promotion of Thl cell activity and the inhibition of Th2 and Th17 cell response. The results suggest that lactoferrin may be a new preparation for the prevention and treatment of allergic rhinitis in the future.
【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

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