本文選題：變應(yīng)性鼻炎 + IL-6��； 參考：《山東大學(xué)》2016年博士論文

【摘要】：目的目前已有多個(gè)研究發(fā)現(xiàn),白介素6(IL-6)基因多態(tài)性是多種免疫相關(guān)疾病的易感基因。最近的研究顯示,在過(guò)敏性呼吸系統(tǒng)疾病中,IL-6擔(dān)當(dāng)重要角色。有關(guān)數(shù)據(jù)顯示,IL-6的表達(dá)同變應(yīng)性鼻炎的發(fā)病之間存在一定的關(guān)系,本研究通過(guò)三部分實(shí)驗(yàn)來(lái)探討IL-6基因多態(tài)性與中國(guó)漢族人群變應(yīng)性鼻炎易感性之間是否相關(guān)性。方法(1)采用HE染色和免疫組織化學(xué)法分別檢測(cè)45例變應(yīng)性鼻炎患者下鼻甲組織、15例鼻中隔偏曲患者下鼻甲組織(對(duì)照組)的病理組織學(xué)變化以及IL-6的表達(dá)。(2)收集265例變應(yīng)性鼻炎患者的外周靜脈血及265例對(duì)照組的外周靜脈血樣本,對(duì)兩組樣本進(jìn)行病例對(duì)照研究。提取血液樣本中的DNA,并對(duì)DNA樣本中IL-6基因的兩個(gè)多態(tài)位點(diǎn)(rs1800795和rs1800796)進(jìn)行基因分型,探討IL-6的基因多態(tài)性與變應(yīng)性鼻炎易感性的關(guān)系。基因分型采取PCR-RFLP和直接測(cè)序的法。(3) 利用Balb/c小鼠建立卵清蛋白致敏的變應(yīng)性小鼠模型,按末次激發(fā)后處死時(shí)間分為6組(30min、1h、2h、6h、12h、24h),同時(shí)使用生理鹽水作為對(duì)照組,每組各5只小鼠。取各組小鼠鼻黏膜組織,利用HE染色法檢測(cè)各組小鼠鼻黏膜組織的病理組織學(xué)變化情況,western blot法檢測(cè)IL-6在各組小鼠鼻黏膜組織中的表達(dá)情況。結(jié)果(1)HE染色結(jié)果表明,變應(yīng)性鼻炎患者的鼻黏膜上皮組織發(fā)生部分脫落,視野下能夠見(jiàn)到杯狀細(xì)胞增生,組織存在水腫現(xiàn)象,腺體增生,血管擴(kuò)張,在上皮組織間可見(jiàn)到醫(yī)以嗜酸性粒細(xì)胞和淋巴細(xì)胞為主的大量炎細(xì)胞浸潤(rùn),其中還包括嗜堿性粒細(xì)胞、中性粒細(xì)胞等。對(duì)兩組組織切片中嗜酸性細(xì)胞進(jìn)行計(jì)數(shù),結(jié)果表明變應(yīng)性鼻炎組嗜酸性粒細(xì)胞浸潤(rùn)顯著,為(31.92±2.95),正常對(duì)照組為(3.83±2.03),變應(yīng)性鼻炎組明顯高于正常對(duì)照組,兩者相比差異顯著(P=0.0010.05); western blot檢測(cè)結(jié)果表明,IL-6蛋白在變應(yīng)性鼻炎患者鼻黏膜組織中的相對(duì)表達(dá)量為(0.40±0.16),而在正常對(duì)照組下鼻甲組織中的相對(duì)表達(dá)量為(0.26±0.14),變應(yīng)性鼻炎組明顯高于正常對(duì)照組(P=0.0030.05)。(2)對(duì)IL-6基因多態(tài)性進(jìn)行分析,結(jié)果表明IL-6 rs1800795等位基因頻率在變應(yīng)性鼻炎患者與對(duì)照組中存在顯著差異(χ2=4.52,P=0.03)；多因素logistic回歸分析表明,相較于G等位基因,IL-6rs1800795的C等位基因具有更高的變應(yīng)性鼻炎發(fā)病風(fēng)險(xiǎn),OR值為1.31(1.01～1.68)。(3) 動(dòng)物行為學(xué)觀察結(jié)果表明,變應(yīng)性鼻炎小鼠模型造模成功；HE染色結(jié)果表明,各變應(yīng)性鼻炎模型組小鼠的鼻腔黏膜上皮均出現(xiàn)不同程度的結(jié)構(gòu)紊亂,同時(shí)還可見(jiàn)充血、水腫以及黏膜層增厚等現(xiàn)象,此外還伴有黏膜上皮組織壞死以及脫落等,纖毛上皮可見(jiàn)有融合現(xiàn)象出現(xiàn),細(xì)胞核發(fā)生形變,形狀不規(guī)則,柱狀細(xì)胞以及杯狀細(xì)胞增生,血管擴(kuò)張并增生,大量肥大細(xì)胞、中性粒細(xì)胞以及嗜酸性粒細(xì)胞、淋巴細(xì)胞浸潤(rùn)。Western blot檢測(cè)結(jié)果表明,各組小鼠鼻黏膜組織中均有IL-6蛋白的表達(dá),其中在30 min組中的相對(duì)表達(dá)量為0.142±0.064,在1h組中的相對(duì)表達(dá)量為0.214±0.104,在2h組中相對(duì)表達(dá)量為0.274±0.092,在6h組中的相對(duì)表達(dá)量為0.324±0.122,然后隨著時(shí)間的延長(zhǎng)呈逐漸下降趨勢(shì),在12h組中的相對(duì)表達(dá)量為0.236+0.059,在24h組中的表達(dá)量為0.172±0.058。與對(duì)照組的相對(duì)表達(dá)量0.068±0.020相比,實(shí)驗(yàn)組小鼠鼻黏膜組織中IL-6蛋白的表達(dá)量較正常組增高。結(jié)論IL-6在變應(yīng)性鼻炎患者鼻黏膜組織中呈高表達(dá),且變應(yīng)性鼻炎的易感性與IL-6基因多態(tài)性顯著相關(guān)。
[Abstract]:Objective a number of studies have found that the interleukin 6 (IL-6) gene polymorphism is a susceptible gene for a variety of immune related diseases. Recent studies have shown that IL-6 plays an important role in allergic respiratory diseases. The relevant data show that there is a relationship between the expression of IL-6 and the incidence of allergic rhinitis. This study is conducted through three parts of the study. The correlation between IL-6 gene polymorphism and allergic rhinitis susceptibility in Chinese Han population was investigated. Methods (1) the histopathological changes in inferior turbinate tissue of 45 patients with allergic rhinitis and 15 cases of nasal septum deviation patients were detected by HE staining and immunohistochemistry, and the table of IL-6 (2) collect the peripheral venous blood of 265 patients with allergic rhinitis and 265 cases of the peripheral venous blood samples from the control group, carry out a case-control study on the two groups of samples, extract the DNA in the blood samples, and classify the two polymorphic loci of the IL-6 gene (rs1800795 and rs1800796) in the DNA sample, and explore the gene polymorphism and allergy of the IL-6. The relationship between the susceptibility of sexual rhinitis. The genotyping was made by PCR-RFLP and direct sequencing. (3) the allergic mice induced by ovalbumin were established by Balb/c mice. The time of death was divided into 6 groups (30min, 1H, 2h, 6h, 12h, 24h), and the physiological salt water was used as the control group, and 5 mice in each group were taken as the control group, and the nasal mucosa group of each group was taken. The pathological changes of nasal mucosa in each group were detected by HE staining. The expression of IL-6 in nasal mucosa of each group was detected by Western blot. Results (1) the results of HE staining showed that the nasal epithelium of the allergic rhinitis patients were separated and the goblet cell hyperplasia could be seen in the field of vision. There is edema, hyperplasia of glands and dilatation of blood vessels. A large number of inflammatory cells, mainly eosinophils and lymphocytes, are seen between the epithelial tissues, including basophils and neutrophils. The eosinophils in the two groups of tissue sections are counted, and the results show eosinophilic granulocyte immersion in allergic rhinitis group. It was significant (31.92 + 2.95), the normal control group was (3.83 + 2.03), the allergic rhinitis group was significantly higher than the normal control group, and the difference was significant (P=0.0010.05). The results of Western blot detection showed that the relative expression of IL-6 protein in the nasal mucosa of patients with allergic rhinitis was (0.40 + 0.16), but in the normal control group, the inferior turbinate tissue was in the normal control group. The relative expression amount was (0.26 + 0.14), the allergic rhinitis group was significantly higher than that of the normal control group (P=0.0030.05). (2) the IL-6 gene polymorphism was analyzed. The results showed that the IL-6 rs1800795 allele frequency was significantly different in the allergic rhinitis patients and the control group (x 2= 4.52, P=0.03), and the multiple factor Logistic regression analysis showed that it was compared with G. The allele of the allele, IL-6rs1800795 C allele had a higher risk of allergic rhinitis, the OR value was 1.31 (1.01 ~ 1.68). (3) the animal behavior observation showed that the model of allergic rhinitis mice model was successful, and the HE staining results showed that the nasal mucosa epithelium of each allergic rhinitis model group had different degree of structural turbulence. At the same time, hyperemia, edema, and thickening of mucous membrane were also seen, in addition to necrosis and exfoliation of epithelial tissue of mucous membrane. Ciliated epithelium showed fusion phenomenon, nuclear deformation, irregular shape, columnar cells and goblet cells hyperplasia, vasodilatation and hyperplasia, large numbers of mast cells, neutrophils, and neutrophils. The results of.Western blot detection in acid granulocyte and lymphocyte infiltration showed that the expression of IL-6 protein in the nasal mucosa of each group was 0.142 + 0.064 in the 30 min group, the relative expression in the 1H group was 0.214 + 0.104, the relative expression in the 2H group was 0.274 + 0.092, and the relative expression in the 6h group was 0.3. 24 + 0.122, and then gradually decreasing with time, the relative expression in 12h group was 0.236+0.059, the expression amount in 24h group was 0.172 + 0.058. and the relative expression of control group was 0.068 + 0.020. The expression of IL-6 protein in the nasal mucosa of the experimental group was higher than that of the normal group. Conclusion IL-6 is in allergic rhinitis. The expression of IL-6 gene was highly expressed in nasal mucosa, and the susceptibility of allergic rhinitis was significantly correlated with the polymorphism of the gene.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R765.21

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 郝曉瑞;;用鼻內(nèi)鏡下聚焦超聲療法治療變應(yīng)性鼻炎的效果觀察[J];當(dāng)代醫(yī)藥論叢;2015年22期

2 葉實(shí)明;張俊中;關(guān)兵;王瑩;大山;;變應(yīng)性鼻炎的手術(shù)治療及臨床療效分析[J];中國(guó)中西醫(yī)結(jié)合耳鼻咽喉科雜志;2015年05期

3 徐艷;馬梅;張宗強(qiáng);;通竅鼻炎顆粒聯(lián)合針刺治療過(guò)敏性鼻炎及對(duì)患者血清IL-4,IL-6及IL-10的影響[J];中國(guó)實(shí)驗(yàn)方劑學(xué)雜志;2015年14期

4 龔霄陽(yáng);程雷;;變應(yīng)性鼻炎的診治現(xiàn)狀與進(jìn)展[J];中國(guó)中西醫(yī)結(jié)合耳鼻咽喉科雜志;2015年03期

5 馮娟;范宇琴;雍軍;阿依恒·曲庫(kù)爾汗;胡斌;張華;;新疆維吾爾、漢族變應(yīng)性鼻炎患者IgE和IFN-γ水平及其與鼻黏膜嗜酸性粒細(xì)胞浸潤(rùn)的相關(guān)性研究[J];新疆醫(yī)科大學(xué)學(xué)報(bào);2015年06期

6 胡海芳;范宇琴;王燕;陽(yáng)玉萍;張華;;新疆維吾爾、漢族CD14基因-159C/T多態(tài)性與變應(yīng)性鼻炎關(guān)聯(lián)分析[J];新疆醫(yī)科大學(xué)學(xué)報(bào);2015年06期

7 史軍;劉玉;嚴(yán)道南;;鼻敏感方對(duì)變應(yīng)性鼻炎大鼠鼻腔黏膜炎性反應(yīng)的影響[J];中華中醫(yī)藥雜志;2015年04期

8 紀(jì)東;桂曉鐘;江萬(wàn)進(jìn);王琴;;安徽蕪湖地區(qū)變應(yīng)性鼻炎患兒家居環(huán)境塵螨變應(yīng)原的分布特征及影響因素分析[J];臨床耳鼻咽喉頭頸外科雜志;2015年05期

9 趙璐;孫秀英;喻意美;李文光;楊玉霞;莫正政;;兒童過(guò)敏性結(jié)膜炎與變應(yīng)性鼻炎的相關(guān)性及鼻眼聯(lián)合治療的研究分析[J];臨床和實(shí)驗(yàn)醫(yī)學(xué)雜志;2015年03期

10 劉爭(zhēng);王男;;兒童變應(yīng)性鼻炎的診斷與治療[J];臨床耳鼻咽喉頭頸外科雜志;2015年03期

相關(guān)會(huì)議論文 前1條

1 顧曉娜;;變應(yīng)性鼻炎治療進(jìn)展[A];中華中醫(yī)藥學(xué)會(huì)耳鼻喉科分會(huì)第十九屆學(xué)術(shù)交流會(huì)暨貴州省中西醫(yī)結(jié)合學(xué)會(huì)耳鼻咽喉分會(huì)第二次學(xué)術(shù)交流會(huì)論文匯編[C];2013年

相關(guān)碩士學(xué)位論文 前2條

1 張亮;變應(yīng)性鼻炎患者血清中趨化因子CCL17及CCL22的表達(dá)及臨床意義[D];南昌大學(xué);2014年

2 李瑩;寧夏地區(qū)回、漢人群變應(yīng)性鼻炎與MRPL4基因多態(tài)性分析[D];寧夏醫(yī)科大學(xué);2014年

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