IL-17及IL-6在慢性鼻窦炎伴鼻息肉患者发病机制中的探讨

发布时间：2018-07-03 09:08

本文选题：慢性鼻窦炎伴鼻息肉 + 白细胞介素-17　；参考：《河北医科大学》2011年硕士论文

【摘要】：目的:慢性鼻窦炎伴鼻息肉(chronic rhinosinusitis with nasal polyps, CRSwNP)是上呼吸道炎症性疾病,其病理过程是复杂的,表现为上皮细胞分泌增强和鳞状上皮化,黏膜固有层基底膜增厚,细胞外基质积聚和胶原沉积,这种结构的改变与炎症细胞浸润相关。但其发病机理尚不是很明确。IL-17被认为在下呼吸道重建和慢性炎症的形成中起着关键的作用。尽管IL-17细胞因子家族是近些年新发现的,但最近研究认为它是引起自身免疫性疾病和炎性疾病的关键因素。细胞因子IL-17在促进炎症的过程中起着重要的作用[1]。众所周知,IL-6是能够诱导分化Th17细胞的细胞因子[2],而Th17细胞以分泌IL-17为主,IL-17的主要功能是刺激间质细胞分泌IL-6、IL-8、GM-CSF、前列腺素E2和NO[3-7],同时,IL-17还促进支气管纤维细胞合成IL-6和IL-8。曾有学者报道IL-17在哮喘中表达增强,嗜酸性粒细胞是IL-17主要来源之一,证明了IL-17在气道重构中的作用[8]。目前已知,IL-6在细胞因子IL-17产生过程中起着重要的作用,它也是在各种炎症性疾病发病机制中起作用的细胞因子,在目前的研究中,已经证明了IL-6在慢性鼻窦炎中起作用。虽然IL-6已经被认为是慢性鼻窦炎中炎症发生的标志,但是其在慢性鼻窦炎伴鼻息肉发病机理中的作用尚未见报道。而IL-17作为最近较新的细胞因子,对于其在鼻息肉发病机制中的作用还需进一步研究,本文旨在于通过研究慢性鼻窦炎伴鼻息肉中IL-17和IL-6的表达情况,来进一步探讨IL-17及IL-6在鼻息肉发病过程中的可能作用机理。方法:病例选择、实验分组及取材。本实验分为慢性鼻窦炎伴鼻息肉组和正常下鼻甲粘膜对照组两组。鼻息肉组织、下鼻甲粘膜组织均来自于2009年10月～2010年8月在我科住院者中需行鼻内镜手术的患者。23例鼻息肉标本来自我科行鼻内窥镜鼻窦手术的患者,其中男13例,女10例,年龄在20-65岁,平均年龄在48.5岁,19例正常下鼻甲粘膜来自我科鼻中隔偏曲伴下鼻甲肥大的患者,其中男10例,女9例,年龄在25-63岁,平均年龄在45岁。全部病例均无变应性鼻炎、哮喘等变态反应史,排除其他全身疾病,并术前4周未使用抗生素、皮质类固醇激素及抗组胺药等药物治疗。标本经10%多聚甲醛固定,常规脱水,石蜡包埋,组织切片,HE染色用于观察炎性细胞浸润情况,并在高倍视野观察嗜酸性粒细胞。免疫组织化学染色用于观察IL-17,IL-6的表达部位及表达情况。所有资料均运用SPSS13.0进行统计分析,采用Wilcoxon秩和检验,卡方检验和相关分析处理数据,以α=0.05作为检验标准。P0.05有统计学意义。结果: 1 HE染色:在鼻息肉组织中可见假复层柱状纤毛上皮覆盖,上皮下为水肿的疏松结缔组织,还可见有不规则的囊性扩张的腺体,并有不同程度的炎性细胞浸润。其中存在着大量的嗜酸性粒细胞的浸润明显高于下鼻甲组织(P0.01)。 2免疫组化染色可见IL-17主要在鼻息肉组织中嗜酸性粒细胞,浆细胞和中性粒细胞胞质中,少量的在浆液腺泡也有阳性表达。IL-17在鼻息肉组中的表达显著高于对照组(P0.01)。 3 IL-6的阳性表达在鼻息肉黏膜下浸润的炎性细胞、成纤维细胞、少量血管内皮细胞的胞质或胞膜上,间质也偶有表达。IL-6在两组间差异有显著性意义(P0.01)。 4 IL-17和IL-6两者在鼻息肉中表达存在着明显的相关性,相关系数r=0.77(P0.01)。结论: 1鼻黏膜中大量嗜酸性粒细胞浸润是慢性鼻窦炎伴鼻息肉的一个重要病理学特征。 2慢性鼻窦炎伴鼻息肉患者中Th17细胞高表达可能是一个重要原因。 3 IL-6可能协同Th17细胞参与慢性鼻窦伴鼻息肉的发生发展。 4在慢性鼻窦炎伴鼻息肉中,IL-17及IL-6之间密切相关,或许可以为慢性鼻窦炎伴鼻息肉的治疗提供一条新思路。
[Abstract]:Objective: chronic nasosinusitis with nasal polyps (chronic rhinosinusitis with nasal polyps, CRSwNP) is an inflammatory disease of the upper respiratory tract. Its pathological process is complex, characterized by enhanced secretion and squamous epithelialization of epithelial cells, thickening of the basilar membrane of the lamina propria, accumulation of extracellular matrix and deposition of collagen, such structural changes and inflammatory cells The pathogenesis is not yet very clear that.IL-17 is considered to play a key role in the reconstruction of the lower respiratory tract and the formation of chronic inflammation. Although the IL-17 cytokine family is newly discovered in recent years, the recent study suggests that it is a key factor in the cause of autoimmune diseases and inflammatory diseases. Cytokine IL-17 is promoting. [1]. is known to play an important role in the process of inflammation, as is known to all, IL-6 is the cytokine [2] that can induce the differentiation of Th17 cells, while Th17 cells secrete IL-17, and the main function of IL-17 is to stimulate interstitial cells to secrete IL-6, IL-8, GM-CSF, prostaglandin E2 and NO[3-7]. Scholars have reported that the expression of IL-17 in asthma is enhanced. Eosinophils are one of the main sources of IL-17. The role of IL-17 in airway remodeling is now known. [8]. is known to play an important role in the production of cytokine IL-17. It is also a cytokine that plays a role in the pathogenesis of various inflammatory diseases. IL-6 has been shown to play a role in chronic nasosinusitis. Although IL-6 has been identified as a marker of inflammation in chronic sinusitis, its role in the pathogenesis of chronic sinusitis with nasal polyps has not yet been reported. And the role of IL-17 as a recent more new cytokine in the pathogenesis of nasal polyps is still needed. One step is to investigate the possible mechanism of IL-17 and IL-6 in the pathogenesis of nasal polyps by studying the expression of IL-17 and IL-6 in chronic rhinosinusitis with nasal polyps.
Methods: the case selection, the experimental group and the materials were divided into two groups: chronic nasosinusitis with nasal polyps and normal inferior turbinate mucosa. The nasal polyps and inferior turbinate mucous tissue were from October 2009 to August 2010 in the patients who had to be operated on the nasal endoscope in our hospital..23 nasal polyps from our department were from the nasal endoscopy. The patients with endoscopic sinus surgery were 13 male and 10 female, with the age of 20-65 years, the average age was 48.5 years old. 19 cases of normal inferior turbinate mucous membrane came from the patients with partial septum and inferior turbinate hypertrophy of the nasal septum, including 10 men, 9 women, the age of 25-63, and the average age of 45. All cases had no allergic rhinitis, asthma and other allergy history, excluded. Other systemic diseases were treated with antibiotics, corticosteroids and antihistamine drugs 4 weeks before operation. The specimens were fixed with 10% polyformaldehyde, routine dehydration, paraffin embedding, tissue section, HE staining to observe the infiltration of inflammatory cells and observing eosinophils at high magnification. Immunohistochemical staining was used to observe IL -17, IL-6 expression and expression. All data were statistically analyzed by SPSS13.0, using Wilcoxon rank sum test, chi square test and correlation analysis processing data, with a statistical significance of alpha =0.05 as a test standard.P0.05.
Result:
1 HE staining: the false stratified columnar ciliated epithelium is covered in the nasal polyps, the epithelia is a loose connective tissue with edema, and there are irregular cystic dilatation glands with varying degrees of inflammatory cell infiltration. There are a large number of eosinophils that are significantly higher than the inferior turbinate (P0.01).
2 immunohistochemical staining showed that IL-17 was mainly in the eosinophils, plasma cells and neutrophils in the nasal polyps, and a small amount in the serous acinus and positive expression of.IL-17 in the nasal polyp group was significantly higher than that in the control group (P0.01).
The positive expression of 3 IL-6 was in the inflammatory cells infiltrating under the nasal polyps, the fibroblasts, the cytoplasm or the membrane of a small amount of vascular endothelial cells, and the occasional expression of the interstitial.IL-6 had significant difference between the two groups (P0.01).
4 there was a significant correlation between the expression of IL-17 and IL-6 in nasal polyps, and the correlation coefficient r=0.77 (P0.01).
Conclusion:
1 the infiltration of eosinophils in nasal mucosa is an important pathological feature of chronic sinusitis and nasal polyps.
2 the high expression of Th17 cells may be an important reason for chronic sinusitis and nasal polyps.
3 IL-6 may cooperate with Th17 cells to participate in the development of chronic sinuses and nasal polyps.
4 there is a close correlation between IL-17 and IL-6 in chronic sinusitis and nasal polyps. It may provide a new idea for the treatment of chronic sinusitis and nasal polyps.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2011
【分类号】：R765.21

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