白介素25、白介素13与血管内皮生长因子在鼻息肉组织中的表达及相关性分析

发布时间：2018-03-17 08:11

本文选题：鼻息肉　切入点：慢性鼻窦炎　出处：《承德医学院》2017年硕士论文　论文类型：学位论文

【摘要】：鼻息肉(nasal polyps,NP)乃鼻科常见病、多发病,文献报道的欧洲地区成年人发病率约1~4%,多伴随鼻腔、鼻窦粘膜的慢性炎性改变,由于其病因的错综复杂和术后极易复发的特性故而在耳鼻喉科疾病中占重要地位。鼻息肉发病原因不明,细胞因子在引起鼻息肉发病的众多病因中备受关注,无论是鼻粘膜的高度水肿、粘膜下层间质及血管的增生、还是腺体分泌活跃和固有层炎细胞浸润等都与细胞因子有多多少少的关联。本文通过免疫组织化学SP法检测白介素25(interleukin 25,IL-25)、白介素13(interleukin 13,IL-13)和血管内皮生长因子(vascular endothelial growth factor,VEGF)三者在息肉中的表达、分布,阐述三者在鼻息肉中的相关关系,探讨细胞因子(cytokine,CK)在息肉中发挥的作用。目的:本实验通过实验研究IL-25、IL-13和VEGF三个因子在鼻息肉组织、筛窦粘膜组织、正常下鼻甲组织中的表达、分布,来探讨IL-25、IL-13和VEGF在息肉的形成过程中所发挥的效应以及三者之间是否存在一定的相互影响,从而为更全面的了解息肉的发病机理,为进一步探讨息肉的病因及非手术治疗提供了分子基础和新的思绪。材料与方法:本实验分成鼻息肉组,慢性鼻窦炎筛窦黏膜组,正常下鼻甲对照组三组。取在(2014年3月~2015年7月期间)保定市第一医院行鼻内窥镜手术治疗的慢性鼻窦炎伴有息肉、慢性鼻窦炎不伴有息肉及鼻中隔偏曲并伴下鼻甲增生的患者标本为实验材料。鼻息肉组织标本30例均来自慢性鼻窦炎伴有息肉患者:男16例,女14例,年龄18~65岁;筛窦黏膜组织标本30例均来自慢性鼻窦炎不伴有息肉患者:男16例,女14例,年龄18~60岁;正常下鼻甲黏膜组织标本10例均来自鼻中隔偏曲伴有下鼻甲增生患者:男6例,女4例;年龄18~55岁。经检查和询问病史,全数入选者均排除变应性鼻炎、支气管哮喘、阿司匹林耐受不良(aspirin intolerance)和其他器官的重大疾病。全部组织标本经4%甲醛固定,酒精脱水,石蜡包裹,组织切片。之后行常规HE染色,并用免疫组化SP法检测IL-25、IL-13和VEGF三者在上述标本中的表达和分布。应用SPSS19.0版数据软件对所得结果进行相应统计学分析。结果:1苏木精-伊红染色光镜下显示:鼻息肉组织、筛窦粘膜组织中嗜酸性粒细胞浸润明显增加,分布局限于粘膜上皮下的血管以及腺体周围。而嗜酸性粒细胞浸润现象在正常鼻黏膜组织鲜少见到。组间两两对比差异均有意义(P0.01)。2 IL-25在鼻息肉、筛窦粘膜及下鼻甲组织中的表达和分布IL-25在息肉组织中表达显著,呈强阳性,在筛窦粘膜中呈阳性表达,表达部位主要分布在嗜酸性粒细胞和中性粒细胞的胞质内,少数在上皮层细胞和间质腺泡内亦有表达,在正常的下鼻甲黏膜中表达显弱阳性。IL-25在鼻息肉组、筛窦粘膜组及正常的下鼻甲黏膜组中的阳性表达率依次为83.3%、73.3%、10%,组间两两对比差异均有意义(P0.01)。3 IL-13在鼻息肉、筛窦粘膜及下鼻甲组织中的表达和分布IL-13在鼻息肉和筛窦粘膜中的分布集中在上皮下组织的炎细胞内,定位在包质或胞膜,标准的染色呈棕褐色或棕黄色。IL-13在正常的下鼻甲黏膜中显现弱阳性表达。IL-13在息肉组、筛窦粘膜组及正常下鼻甲黏膜组中的阳性率分别为90.0%、80.0%、10%,组间两两对比差异均具有意义(P0.01)。4 VEGF在鼻息肉、筛窦粘膜及下鼻甲组织中的表达和分布VEGF在息肉及筛窦粘膜中集中定位在上皮层细胞、附近腺管和周围血管以及血管内皮细胞,基底膜周围的炎性细胞内亦表达,多定位于胞质,少数定位于胞核。VEGF在正常下鼻甲黏膜中的表达显现弱阳性。VEGF在息肉组、筛窦粘膜组及下鼻甲组中的阳性表达率分别为86.7%、76.7%、20%,组间两两对比差异均具有意义(P0.01)。5 IL-25、IL-13和VEGF在息肉组织中表达的相关性分析相关性分析显示:鼻息肉组织中IL-25与IL-13的表达呈正相关性(r=0.400,P0.01),IL-13与VEGF的表达呈正相关性(r=0.632,P0.01),IL-25与VEGF的表达亦呈正相关性(r=0.738,P0.01)。结论:1鼻息肉的重要组织病理特性之一就是Eos的浸润增多。2 IL-25可以诱导Th2型免疫应答,增强前炎反应,促进Th2类细胞因子的分泌而使炎症反应级联放大,引导并刺激组织分泌炎性介质使Eos聚集和上皮细胞增生,从而发生鼻黏膜的息肉样变化。3 IL-13可以激活Th2并抑制Th1免疫应答,调节T、B细胞功能,促使Ig E生成增加,引起炎细胞浸润,诱导Eos游移,介入鼻息肉的形成。4 VEGF可以诱发组织新生出大量微血管,加快鼻息肉的生长,之后新生血管血浆外渗,鼻腔及鼻窦内组织液集聚,组织水肿,局部组织受到挤压变形,上皮层断裂,息肉形成。5 IL-25、IL-13与VEGF三者在息肉中的表达两两均呈正性相关关系,提示三个细胞因子可能协同参与了息肉的形成过程,同时证实了鼻息肉的出现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.

【学位授予单位】：承德医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R765.25

【参考文献】