本文選題：鼻息肉　切入點(diǎn)：慢性鼻竇炎　出處：《承德醫(yī)學(xué)院》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：鼻息肉(nasal polyps,NP)乃鼻科常見病、多發(fā)病,文獻(xiàn)報(bào)道的歐洲地區(qū)成年人發(fā)病率約1~4%,多伴隨鼻腔、鼻竇粘膜的慢性炎性改變,由于其病因的錯(cuò)綜復(fù)雜和術(shù)后極易復(fù)發(fā)的特性故而在耳鼻喉科疾病中占重要地位。鼻息肉發(fā)病原因不明,細(xì)胞因子在引起鼻息肉發(fā)病的眾多病因中備受關(guān)注,無論是鼻粘膜的高度水腫、粘膜下層間質(zhì)及血管的增生、還是腺體分泌活躍和固有層炎細(xì)胞浸潤等都與細(xì)胞因子有多多少少的關(guān)聯(lián)。本文通過免疫組織化學(xué)SP法檢測白介素25(interleukin 25,IL-25)、白介素13(interleukin 13,IL-13)和血管內(nèi)皮生長因子(vascular endothelial growth factor,VEGF)三者在息肉中的表達(dá)、分布,闡述三者在鼻息肉中的相關(guān)關(guān)系,探討細(xì)胞因子(cytokine,CK)在息肉中發(fā)揮的作用。目的:本實(shí)驗(yàn)通過實(shí)驗(yàn)研究IL-25、IL-13和VEGF三個(gè)因子在鼻息肉組織、篩竇粘膜組織、正常下鼻甲組織中的表達(dá)、分布,來探討IL-25、IL-13和VEGF在息肉的形成過程中所發(fā)揮的效應(yīng)以及三者之間是否存在一定的相互影響,從而為更全面的了解息肉的發(fā)病機(jī)理,為進(jìn)一步探討息肉的病因及非手術(shù)治療提供了分子基礎(chǔ)和新的思緒。材料與方法:本實(shí)驗(yàn)分成鼻息肉組,慢性鼻竇炎篩竇黏膜組,正常下鼻甲對照組三組。取在(2014年3月~2015年7月期間)保定市第一醫(yī)院行鼻內(nèi)窺鏡手術(shù)治療的慢性鼻竇炎伴有息肉、慢性鼻竇炎不伴有息肉及鼻中隔偏曲并伴下鼻甲增生的患者標(biāo)本為實(shí)驗(yàn)材料。鼻息肉組織標(biāo)本30例均來自慢性鼻竇炎伴有息肉患者:男16例,女14例,年齡18~65歲;篩竇黏膜組織標(biāo)本30例均來自慢性鼻竇炎不伴有息肉患者:男16例,女14例,年齡18~60歲;正常下鼻甲黏膜組織標(biāo)本10例均來自鼻中隔偏曲伴有下鼻甲增生患者:男6例,女4例;年齡18~55歲。經(jīng)檢查和詢問病史,全數(shù)入選者均排除變應(yīng)性鼻炎、支氣管哮喘、阿司匹林耐受不良(aspirin intolerance)和其他器官的重大疾病。全部組織標(biāo)本經(jīng)4%甲醛固定,酒精脫水,石蠟包裹,組織切片。之后行常規(guī)HE染色,并用免疫組化SP法檢測IL-25、IL-13和VEGF三者在上述標(biāo)本中的表達(dá)和分布。應(yīng)用SPSS19.0版數(shù)據(jù)軟件對所得結(jié)果進(jìn)行相應(yīng)統(tǒng)計(jì)學(xué)分析。結(jié)果:1蘇木精-伊紅染色光鏡下顯示:鼻息肉組織、篩竇粘膜組織中嗜酸性粒細(xì)胞浸潤明顯增加,分布局限于粘膜上皮下的血管以及腺體周圍。而嗜酸性粒細(xì)胞浸潤現(xiàn)象在正常鼻黏膜組織鮮少見到。組間兩兩對比差異均有意義(P0.01)。2 IL-25在鼻息肉、篩竇粘膜及下鼻甲組織中的表達(dá)和分布IL-25在息肉組織中表達(dá)顯著,呈強(qiáng)陽性,在篩竇粘膜中呈陽性表達(dá),表達(dá)部位主要分布在嗜酸性粒細(xì)胞和中性粒細(xì)胞的胞質(zhì)內(nèi),少數(shù)在上皮層細(xì)胞和間質(zhì)腺泡內(nèi)亦有表達(dá),在正常的下鼻甲黏膜中表達(dá)顯弱陽性。IL-25在鼻息肉組、篩竇粘膜組及正常的下鼻甲黏膜組中的陽性表達(dá)率依次為83.3%、73.3%、10%,組間兩兩對比差異均有意義(P0.01)。3 IL-13在鼻息肉、篩竇粘膜及下鼻甲組織中的表達(dá)和分布IL-13在鼻息肉和篩竇粘膜中的分布集中在上皮下組織的炎細(xì)胞內(nèi),定位在包質(zhì)或胞膜,標(biāo)準(zhǔn)的染色呈棕褐色或棕黃色。IL-13在正常的下鼻甲黏膜中顯現(xiàn)弱陽性表達(dá)。IL-13在息肉組、篩竇粘膜組及正常下鼻甲黏膜組中的陽性率分別為90.0%、80.0%、10%,組間兩兩對比差異均具有意義(P0.01)。4 VEGF在鼻息肉、篩竇粘膜及下鼻甲組織中的表達(dá)和分布VEGF在息肉及篩竇粘膜中集中定位在上皮層細(xì)胞、附近腺管和周圍血管以及血管內(nèi)皮細(xì)胞,基底膜周圍的炎性細(xì)胞內(nèi)亦表達(dá),多定位于胞質(zhì),少數(shù)定位于胞核。VEGF在正常下鼻甲黏膜中的表達(dá)顯現(xiàn)弱陽性。VEGF在息肉組、篩竇粘膜組及下鼻甲組中的陽性表達(dá)率分別為86.7%、76.7%、20%,組間兩兩對比差異均具有意義(P0.01)。5 IL-25、IL-13和VEGF在息肉組織中表達(dá)的相關(guān)性分析相關(guān)性分析顯示:鼻息肉組織中IL-25與IL-13的表達(dá)呈正相關(guān)性(r=0.400,P0.01),IL-13與VEGF的表達(dá)呈正相關(guān)性(r=0.632,P0.01),IL-25與VEGF的表達(dá)亦呈正相關(guān)性(r=0.738,P0.01)。結(jié)論:1鼻息肉的重要組織病理特性之一就是Eos的浸潤增多。2 IL-25可以誘導(dǎo)Th2型免疫應(yīng)答,增強(qiáng)前炎反應(yīng),促進(jìn)Th2類細(xì)胞因子的分泌而使炎癥反應(yīng)級聯(lián)放大,引導(dǎo)并刺激組織分泌炎性介質(zhì)使Eos聚集和上皮細(xì)胞增生,從而發(fā)生鼻黏膜的息肉樣變化。3 IL-13可以激活Th2并抑制Th1免疫應(yīng)答,調(diào)節(jié)T、B細(xì)胞功能,促使Ig E生成增加,引起炎細(xì)胞浸潤,誘導(dǎo)Eos游移,介入鼻息肉的形成。4 VEGF可以誘發(fā)組織新生出大量微血管,加快鼻息肉的生長,之后新生血管血漿外滲,鼻腔及鼻竇內(nèi)組織液集聚,組織水腫,局部組織受到擠壓變形,上皮層斷裂,息肉形成。5 IL-25、IL-13與VEGF三者在息肉中的表達(dá)兩兩均呈正性相關(guān)關(guān)系,提示三個(gè)細(xì)胞因子可能協(xié)同參與了息肉的形成過程,同時(shí)證實(shí)了鼻息肉的出現(xiàn)系多因子交叉作用的后果。
[Abstract]:Nasal polyps (nasal polyps NP) is a common disease of nasal disease, reported in Europe adults, the incidence rate of about 1~4%, with nasal sinus mucosa, chronic inflammatory changes, due to the characteristics and the causes of the perplexing operation and easy to relapse after the play an important role in the pathogenesis of diseases in Department of ENT. Nasal polyps is unknown, cytokines caused concern in many causes of nasal polyps, whether highly edema of nasal mucosa, submucosal interstitial and vascular hyperplasia, or glandular secretion and active lamina propria inflammatory cell infiltration are more or less associated with cytokines. Through immunohistochemical detection of interleukin SP act 25 (interleukin 25, IL-25), interleukin 13 (interleukin 13, IL-13) and vascular endothelial growth factor (vascular endothelial, growth factor, VEGF) the distribution and expression of three in polyps, three states The correlation in nasal polyps and to explore the effects of cytokines (cytokine, CK) to play in the role of polyps. Objective: through this experiment, the experimental study of IL-25, IL-13 and VEGF three factor in nasal polyps, ethmoid sinus mucosa, the expression distribution, normal inferior turbinate tissues, to explore whether there is IL-25. A certain interaction between effect played by IL-13 and VEGF in the formation of polyps in the process as well as the three, which is a more comprehensive understanding of the pathogenesis of polyps, provide a molecular basis and new ideas for the further study of the etiology of polyps and non operative treatment. Materials and methods: the experiment was divided into nasal polyps, chronic sinusitis of ethmoid mucosa of inferior turbinate group, normal control group three group. (in March 2014 ~2015 in July) the first hospital of Baoding city underwent nasal endoscopic surgery for chronic sinusitis with polyps, chronic sinusitis with polyps And the deviation of nasal septum with inferior turbinate hyperplasia were collected as experimental materials. The nasal polyp tissue specimens from 30 patients were from patients with chronic sinusitis with polyps: male 16 cases, female 14 cases, age 18~65 years old; ethmoid mucosa tissue samples from 30 cases of chronic sinusitis with polyps from patients: male 16 cases, female 14 cases age, 18~60 years old; normal mucosa tissue samples from 10 cases were accompanied with nasal septum deviation of inferior turbinate hyperplasia patients: 6 cases were male, 4 were female; the age of 18~55 years old. After inspection and history, all subjects were excluded from the allergic rhinitis, bronchial asthma, aspirin intolerance (aspirin intolerance) and major diseases other organs. All the tissues were fixed by 4% formaldehyde, ethanol dehydration, paraffin coated, tissue sections. After routine HE staining and immunohistochemical detection of IL-25 SP method, the expression and distribution of IL-13 and VEGF three in the samples. Application of SPSS19.0 software version of the data on the results of the corresponding statistical analysis. Results: 1 hematoxylin eosin staining under light microscope showed: nasal polyps, ethmoid sinus mucosa tissue eosinophilia was significantly increased, the distribution is confined to the mucosal epithelium and gland around the blood vessels. And eosinophil infiltration phenomenon rarely seen in normal nasal mucosa tissues. The differences were compared between the 22 groups was significant (P0.01).2 IL-25 in nasal polyps, the expression and distribution of IL-25 in the ethmoid sinus mucosa and turbinate tissue expression significantly in polyp tissues, was strongly positive, positive expression in the ethmoid sinus mucosa, was mainly distributed in the cytoplasm of eosinophils cells and neutrophils, few in epithelial cells and stromal acini have weak positive expression of.IL-25 in nasal polyp group expression in normal mucosa of inferior turbinate, ethmoid sinus mucosa and the normal The positive expression rate in the group of nasal mucosa were 83.3%, 73.3%, 10%, between the 22 groups were significant difference (P0.01) of.3 IL-13 in nasal polyps, the distribution of expression and distribution of IL-13 in the ethmoid sinus mucosa and turbinate tissue in nasal polyps and ethmoid sinus mucosa in inflammatory cells concentrated in woven epithelial group. Located in the cytosol membrane bag, the standard dyed brown or brown yellow.IL-13 in normal mucosa of inferior turbinate revealed weak expression of.IL-13 in nasal polyp group, the positive rate in the group of normal group and ethmoid sinus mucosa were 90%, 80%, 10%, the difference between the two groups have significance 22 (P0.01.4 VEGF) in nasal polyps, the expression and distribution of VEGF in the ethmoid sinus mucosa and turbinate tissue in polyps and ethmoid sinus mucosa in centrally located in the epithelial layer of cells near the gland and peripheral vascular and vascular endothelial cells, basement membrane surrounding inflammatory cells also The expression of multiple in cytoplasm, the expression of a few localized in the nucleus of.VEGF in the inferior turbinate mucosa of.VEGF appeared weak positive in polyp group, positive group and ethmoid sinus mucosa of inferior turbinate group rates were 86.7%, 76.7%, 20%, the difference between the two groups are 22 (P0.01).5 IL-25, meaning analysis of correlation between the expression of IL-13 and VEGF in polyp tissues correlation analysis showed that the expression of IL-25 was positively correlated with IL-13 in nasal polyps (r=0.400, P0.01), the expression of IL-13 was positively correlated with VEGF (r=0.632, P0.01), IL-25 and VEGF expression was also positively correlated (r=0.738, P0.01). Conclusion: one of the most important the pathological characteristics of 1 nasal polyps is Eos.2 increased infiltration of IL-25 can induce Th2 immune response, enhancement of inflammatory reaction, promote the secretion of Th2 cytokines and the inflammatory reaction cascade, guide and stimulate the secretion of inflammatory mediators Eos organization The aggregation and proliferation of epithelial cells, changes of.3 IL-13 and polypoid nasal mucosa can activate Th2 and inhibit the immune response of Th1 and regulation of T, B cell function, prompted the Ig to increase E generation, caused by the infiltration of inflammatory cells, induce Eos formation of.4 wavering, VEGF can induce a large number of new tissue micro vascular interventional nasal polyps, accelerate nasal polyps after neovascularization plasma extravasation, nasal cavity and sinus tissue fluid concentration, tissue edema, local tissue by extrusion, epithelial layer fracture, polyp formation.5 and VEGF three IL-25, IL-13 in the polyps in the table 22 showed positive correlation, suggesting that the three cytokines may be involved in the the formation process of polyps, also confirmed the emergence of nasal polyps, multi factor interaction effects.

【學(xué)位授予單位】：承德醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R765.25

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