TNF-α和MMP-9在鼻息肉嗜酸粒细胞浸润过程中的作用

目的:研究鼻息肉组织中TNF-α、MMP-9的表达和意义,并探讨两者表达与嗜酸粒细胞(EOS)浸润的关系.方法:采用原位杂交和免疫组织化学技术,检测鼻息肉组30例息肉组织及对照组10例下鼻甲黏膜组织中TNF-α、MMP-9 mRNA和蛋白的表达;采用苏木精-伊红染色观察鼻息肉和下鼻甲黏膜组织中EOS的浸润情况,并比较分析三者之间的相关性.结果:鼻息肉组织中TNF-α表达的阳性细胞数、阳性血管数及MMP-9阳性细胞数与下鼻甲黏膜组织相比差异有统计学意义(P<0.05);且鼻息肉组织中TNF-α阳性细胞数和阳性血管数均与EOS数存在明显相关性(P<0.05),MMP-9阳性细胞数与EOS数明显相关(P<0.05),TNF-α阳性细胞数与MMP-9阳性细胞数存在相关性(P<0.05).结论:TNF-α、MMP-9在鼻息肉的发病机制中发挥着重要作用,TNF-α可能通过诱导MMP-9的产生促进EOS在鼻息肉中的浸润.     

血红素氧合酶1在变应性鼻炎豚鼠模型的鼻黏膜中的表达

目的:通过制备豚鼠变应性鼻炎动物模型,观察并分析内源性一氧化碳(CO)的限速酶血红素氧合酶1(HO1)在豚鼠鼻黏膜组织中的表达。方法:分别以卵清蛋白致敏制备豚鼠变应性鼻炎动物模型为致敏组及以地塞米松处理作为治疗组,以生理盐水处理作为正常对照组,取豚鼠鼻黏膜,苏木精伊红染色观察炎性细胞浸润,免疫组织化学染色方法观察HO1在各组豚鼠的鼻黏膜组织中的表达情况。结果:在黏膜组织中,炎性细胞的浸润与炎症程度有关,炎性细胞以嗜酸粒细胞(EOS)浸润明显,HO1主要表达在黏膜腺上皮细胞的胞质中,3组中,致敏组鼻黏膜HO1表达明显增强(P<0.01),黏膜下EOS浸润明显(P<0.01),激素治疗组HO1的表达弱于致敏组(P<0.01),黏膜下EOS浸润程度减轻,但强于对照组(P<0.01),组间差异有统计学意义(均P<0.01)。结论:HO1主要表达于鼻黏膜的腺上皮细胞质内,豚鼠变应性鼻炎模型中HO1的表达与炎症的严重程度相关,提示内源性CO可能参与了变应性鼻炎的炎症过程。     

肺表面活性蛋白D与IL-16在变应性鼻炎及鼻息肉中的表达和意义

目的:检测肺表面活性蛋白D(SP-D)及IL-16在变应性鼻炎鼻黏膜组织和鼻息肉组织中的表达情况,探讨SP-D及IL-16在变应性鼻炎和鼻息肉发病中的作用及意义。方法:采用免疫组织化学方法分别检测15例鼻中隔偏曲伴变应性鼻炎患者下鼻甲黏膜组织(变应性鼻炎组)、15例鼻息肉组织(鼻息肉组)和15例下鼻甲黏膜组织(对照组)中SP-D及IL-16表达。结果:SP-D、IL-16在3组中均有表达,但在变应性鼻炎组和鼻息肉组的表达均明显高于对照组(均P<0.01);SP-D和IL-16在变应性鼻炎组和鼻息肉组中的表达相比较差异无统计学意义(P>0.05)。结论:SP-D及IL-16在正常组织和病变组织中均有表达。SP-D可能参与了变应性鼻炎和鼻息肉的炎症反应过程。IL-16是变应性鼻炎和鼻息肉病变中重要的嗜酸粒细胞趋化因子,并增强了嗜酸粒细胞的局部作用,参与了变应性鼻炎和鼻息肉的病变过程。     

IL-17在鼻息肉中的表达及其意义

目的：研究伴变应性体质和不伴变应性体质的鼻息肉患者息肉中IL-17的表达及与病理特征的关系。方法：30例鼻息肉患者根据皮肤点刺实验分为伴变应性体质组和不伴变应性体质组,通过苏木精一伊红染色法嗜酸粒细胞浸润程度评价组织学特征,运用ELISA及RT—PCR方法检测IL-17在鼻息肉中的表达。结果：伴变应性体质组嗜酸粒细胞浸润明显高于不伴变应性体质组（P〈O．01）;两组息肉组织中IL-17蛋白及mRNA水平均显著高于对照组（P〈O．01或P〈0．05）,且变应性体质组IL-17水平明显高于不伴变应性体质组,鼻息肉患者IL-17水平与嗜酸粒细胞浸润呈正相关。结论：IL-17在鼻息肉组织中表达明显上调,且在伴变应性体质组中水平更高,提示IL-17可能在鼻息肉的发病机制中发挥重要作用,变应性因素在鼻息肉形成中可能是通过促进IL-17曲立牛而,卉＇枷曲     

白介素-5在变应性鼻炎鼻黏膜中的表达及意义

目的：了解白介素 5（IL 5）在变应性鼻炎鼻粘膜内浸润的炎性细胞中的表达及分布，探讨IL 5与嗜酸性粒细胞积聚及发病机制的关系。方法：采用免疫组化染色法（SP法）对变应性鼻炎下鼻甲粘膜（A组）、单发鼻息肉组织（B组）、无变应性鼻炎下鼻甲粘膜组织（C组）切片进行IL 5染色，对IL 5染色阳性细胞计数分类，对统计结果行方差分析。结果：A、B两组组织中可见较多的IL 5阳性染色细胞，多见嗜酸性细胞、淋巴细胞、中性粒细胞等阳性染色，两组IL 5阳性细胞总数、Eos计数无统计学差异，但均高于C组（P＜0.01）。结论：IL 5在变应性鼻炎鼻粘膜、鼻息肉组织内浸润的多种炎性细胞中表达，能客观反映免疫或炎症反应的程度，可作为变应性鼻炎诊断评分系统的补充。     

白细胞介素23在变应性鼻炎患者鼻黏膜中的表达及意义

目的:探讨白细胞介素23(IL-23)在变应性鼻炎(AR)患者鼻黏膜中的表达及意义.方法:收集12例AR患者(AR组)下鼻甲黏膜及11例单纯性鼻中隔偏曲患者下鼻甲黏膜(对照组),采用免疫组织化学方法和实时定量RT-PCR方法检测下鼻甲黏膜中IL-23的表达.结果:IL-23p19 mRNA在AR组中的表达水平较对照组明显增高(P<0.01).免疫组织化学显示IL-23蛋白主要表达于黏膜固有层的炎性浸润细胞,AR组鼻黏膜中IL-23阳性细咆数明显高于对照组(P<0.01).IL-23p19mRNA和蛋白表达水平与黏膜固有层总炎性细胞浸润程度及固有层胶原纤沉积程度成显著正相关(对于mRNA表达水平,相关系数分别为0.678和0.834;对于蛋白表达水平,相关系数分别0.644和0.721,均P<0.01).结论:IL-23可能参与了AR的慢性炎症和组织重塑.     

变应性鼻炎神经肽与肥大细胞关系的实验研究

目的:探讨辣椒素治疗实验性变应性鼻炎的机制,进一步研究变应性鼻炎中神经肽与肥大细胞之间的关系。方法:健康SD大鼠30只,随机分为自然对照组、变应性鼻炎组和辣椒素治疗组,每组各10只。用卵清蛋白腹腔注射免疫,继之鼻腔局部免疫建立大鼠变应性鼻炎模型,并进行辣椒素治疗2周,观察各组大鼠行为学改变,取各组动物的鼻黏膜行常规苏木精-伊红染色、甲苯胺蓝染色及免疫组织化学染色,计数并比较肥大细胞在各组之间的差异,观察P物质(SP)在鼻黏膜中分布密度的差异。结果:变应性鼻炎组肥大细胞计数大于自然对照组(P<0.01)。辣椒素治疗组肥大细胞少见,低于变应性鼻炎组(P<0.01);SP的表达低于变应性鼻炎组(P<0.01),但与自然对照组比较差异无统计学意义(P>0.05)。组织中SP的表达与肥大细胞浸润有一定的正相关性(r=0.8252,P<0.05)。结论:辣椒素治疗变应性鼻炎模型可有效减少肥大细胞的浸润,使SP表达减少,各种过敏症状明显改善。     

鼻息肉中嗜酸性粒细胞浸润和活化与白细胞介素5表达

目的通过观察鼻息肉中嗜酸性粒细胞的浸润和活化状态,以及白细胞介素5(interleukin-5,IL-5)的表达水平,揭示二者的关系,探索鼻息肉中嗜酸性粒细胞浸润增多调节的机制。方法对30例鼻息肉组织,分别采用chromotrope2R法标记鼻息肉组织中的嗜酸性粒细胞,采用免疫组织化学ABC法,观察嗜酸性粒细胞的活化状态和IL-5的表达水平,然后进行相关性分析。结果①chromotrope 2R染色可特异性地将嗜酸粒细胞的胞浆染成粉红色,活化嗜酸性粒细胞(EG2阳性细胞)和IL-5阳性细胞胞浆中可见棕褐色颗粒。30例鼻息肉中嗜酸性粒细胞的密度为50.7±16.1/0.25mm2,活化嗜酸性粒细胞的密度为20.7±14.3/0.25mm2,IL-5阳性细胞密度为15.9±5.7/0.25mm2,上述三项指标在变应性患者和非变应性患者比较未见显著性差异(P>0.05);②鼻息肉中IL-5阳性细胞密度与chromotrope2R阳性细胞密度密切相关(y=14.723 2.012x,r=0.642,P<0.01),与EG2阳性细胞密度也存在相关关系(y=11.817 1.092x,r=0.602,P<0.05)。结论嗜酸性粒细胞是鼻息肉组织中IL-5的来源之一,IL-5的表达水平是鼻息肉中嗜酸性粒细胞的浸润和活化的调节因素之一。     

CD30在变应性鼻炎患者鼻黏膜组织中的表达

目的 :探讨CD30在变应性鼻炎患者鼻黏膜组织中的表达 ,分析其在变应性鼻炎发病中的作用。方法 :应用免疫组织化学SP法和苏木精 伊红染色对 31例变应性鼻炎患者的下鼻甲黏膜 (变应性鼻炎组 )和 2 6例肥厚性鼻炎患者的下鼻甲黏膜 (对照组 )标本中CD30的表达进行检测 ,并进行统计学分析。结果 :变应性鼻炎组CD30细胞数显著高于对照组 ,其差异有统计学意义 (P <0 .0 5 )。结论 :在变应性鼻炎的鼻黏膜组织中存在着Th2细胞主导的黏膜反应 ,通过研究CD30的表达水平可了解变应性鼻炎中Th2反应的状态。     

肺表面活性蛋白A在变应性鼻炎鼻黏膜及鼻息肉组织中的表达及意义

目的：肺表面活性蛋白A（SP—A）在呼吸道中发挥重要的宿主防御作用。本研究的目的是了解SP-A在变应性鼻炎鼻黏膜和鼻息肉组织中的表达情况,探讨SP—A在上呼吸道炎症反应性疾病中发挥的作用。方法：采用免疫组织化学方法和间接免疫荧光法分别检测11例变应性鼻炎患者鼻黏膜组织（变应性鼻炎组）、15例鼻息肉患者的息肉组织（鼻息肉组）和7例行鼻中隔偏曲矫正术患者的中鼻甲组织（对照组）中SP-A的表达。结果：免疫组织化学方法结果显示变应性鼻炎组及鼻息肉组中SP—A的表达明显高于对照组（P〈0．05）,变应性鼻炎组及鼻息肉组黏膜下嗜酸粒细胞的数量明显高于对照组（P〈0．05）,变应性鼻炎组及鼻息肉组中SP-A的表达与黏膜下嗜酸粒细胞的数量均呈正相关（r分别为0．81,0．55）;免疫荧光法结果显示SP—A在变应性鼻炎组及鼻息肉组黏膜上皮细胞内的绿色荧光强度高于对照组（P〈0．05）。结论：SP-A可能参与了变应性鼻炎与鼻息肉的炎症反应过程。SP—A在上呼吸道炎症性疾病中的表达,为今后寻找新的治疗方法提供理论思路。     

The concentration and expression of IL-5 in human nasal polyp tissue]

OBJECTIVE: To study the concentration and expression of IL-5 in nasal polyp tissues and explore its significance in the micro-environment differentiation of eosinophils accumulation and clarify the conception of nasal polyposis. METHODS: The concentration and expression of IL-5 in nasal polyp tissues of 40 patients were determined by ELISA and immunohistochemistry, and inferior turbinate mucosa from patients with nasal polyps and healthy volunteers was used as control. RESULTS: 1. IL-5 concentration in the polyp tissues was significantly higher than that in inferion turbinate mucosa(P < 0.05). There was no significant difference in inferion turbinate mucosa between the patients with nasal polyps and healthy volunteers (P > 0.05). IL-5 concentration in polyp tissues was markedly higher in patients with extensive polypoid change of nasal mucosa, history of previous polypectomy and allergic rhinitis compared with those without these features (P < 0.05). IL-5 concentration had no correlation with age and sex (P > 0.05). 2. 80.1% of the eosinophils were positive for IL-5 and 90.9% of IL-5 positive cells were eosinophils. Only 3.7% of the lymphocytes and neutrophils were IL-5 positive, and IL-5 was not detectable in epithelial cells. IL-5 expression in eosinophils of polyp tissues was remarkably stronger than that of the turbinate mucosa (P < 0.05). There was no significant difference in inferion turbinate mucosa between the patients with nasal polyps and healthy volunteers (P > 0.05). IL-5 expression of eosinophils in polyp tissues was significantly stronger in patients with extensive polypoid change of nasal mucosa, history of previous polypectomy and allergic rhinitis compared with those without these features (P < 0.05). There was no significant difference in IL-5 expression in lymphocytes and neutrophils between polyp tissues and inferior turbinate nasal mucosa (both P > 0.05). CONCLUSION: IL-5 is a key protein in eosinophilic pathologic mechanisms in nasal polyp tissues.     

IL-17C expression in nasal epithelial cells of chronic rhinosinusitis with nasal polyposis

Interleukin 17C (IL-17C) is a functionally distinct member of the IL-17 family that is selectively induced in epithelia by bacterial challenge and inflammatory stimuli. The goal of this study was to explore the expression of IL-17C in nasal epithelial cells and their role in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNPs). IL-17C expression was detected using immunohistochemistry (IHC) of the epithelial cell layers and using the western blot assay on whole tissue homogenates from control subjects (n = 10) and CRSwNP patients [10 non-eosinophilic polyps and 10 eosinophilic polyps (EPs)]. Expression of IL-17C and P47-phox were evaluated in the human nasal epithelial cells (RPMI-2650 cells) after treatment with staphylococcal enterotoxin B (SEB) and pretreatment with reactive oxygen species (ROS) scavenger, N-acetyl l-cysteine (NAC). Finally, IL-17C expression was demonstrated in eosinophilic rhinosinusitis murine model using IHC. Epithelial expression of IL-17C was higher in nasal polyps (especially in EPs) compared to control mucosa. SEB increased the expression of IL-17C and P47-phox in RPMI-2650 cells. SEB-induced expressions of both IL-17C and P47-phox were significantly decreased in NAC-pretreated cells. Epithelial expression of IL-17C was significantly higher in experimental mice compared to control mice. SEB-induced IL-17C expression in nasal epithelial cells is mediated by ROS production. This pathway may be associated with the pathogenesis of CRSwNP, especially eosinophilic nasal polyps.     

吸入性氢气清除法鼻粘膜微循环血流量测定

测定国人鼻粘膜微循环血流量。方法 应用Ａｍｅｆｌｗ－Ｈ２微循环测量仪对１３０例鼻粘膜微循环血流一在局部喷雾血管收缩剂前后进行了测量，其中健康成人９８例，鼻息肉患者１８例，应变性鼻炎患者１４例。统计学处理采用ｔ检验。结果 健康成人对照组鼻粘膜微循环血流量大于鼻息肉组及变应性鼻炎组。     

Distribution of rantes and interleukin-5 in allergic nasal mucosa and nasal polyps.

Eosinophil-chemoattracting cytokines are thought to be important in the pathogenesis of allergic inflammation. However, little is known about the presence and significance of RANTES in nasal allergy and nasal polyps, two well-known rhinologic disorders characterized by eosinophil infiltration in the tissue. In order to evaluate the role of RANTES in eosinophil infiltration in vivo, the tissue distributions of RANTES and interleukin-5 (IL-5) and their correlation with eosinophil infiltration were investigated. Nasal mucosa specimens were obtained from 9 allergic and 12 control subjects, and nasal polyps from 6 allergic and 9 nonallergic subjects. All the subjects were divided into 4 groups: normal mucosa, allergic mucosa, nonallergic polyps, and allergic polyps. To identify the cellular localizations of RANTES and IL-5, we used specific immunohistochemical staining. We also investigated the differences in cytokine expression among the 4 groups, and the correlation between cytokine expression and eosinophil infiltration in the tissue. RANTES was expressed in the epithelium, endothelium, and some submucosal cells, while IL-5 was confined to the cells in the submucosa. Expression of both RANTES and IL-5 significantly increased in allergic mucosa and nasal polyps compared to normal mucosa; however, there was no significant difference in their expression between allergic and nonallergic polyps. Both cytokines had a significant correlation between their expression and either total or activated eosinophil numbers. The results of this study suggest that RANTES, as well as IL-5, plays a role in eosinophil recruitment in allergic nasal mucosa and nasal polyps in vivo.     

Expression of Syk is associated with nasal polyp in patients with allergic rhinitis

OBJECTIVE: Numerous signalings are involved in allergic inflammation. The non-receptor protein tyrosine kinase, Syk, is widely expressed in immune-potentiated cells and plays critical roles in initiating signal transduction in response to the activation of cytokine, chemokine and other types of receptors. It has been hypothesized that Syk expression in allergic nasal mucosa and polyps with allergy is different from non-allergic mucosa, and that changes in Syk expression contribute to the activation of allergic reactions. METHODS: We examined whether the expression of Syk is found in allergic nasal mucosa and polyps. We investigated the expression of Syk in 46 nasal mucosa and polyps (14 samples from patients with allergic rhinitis and 32 samples with non-allergic chronic sinusitis) using an immunohistochemical technique. RESULTS: Allergic polyps had more Syk positive cells than non-allergic polyps. Syk positive cells were determined to mainly be eosinophils. There was no difference in Syk expression in the lamina propria and nasal gland between allergic mucosa and non-allergic mucosa. CONCLUSION: Eosinophils in allergic polyps receive an intracellular signal, although the signal is not able to determine the function in the present state. Syk appears to be a promising target molecule for anti-allergic inflammation in allergic rhinitis.     

鼻息肉组织中IL-4 IL-5 IL-6和IL-8的含量及其表达

目的：通过检测鼻息肉组织中IL-4、IL-5、IL-6、IL-8的水平及表达方式,探讨细胞因子在鼻息肉形成中的作用。方法：应用放射免疫法检测54例鼻息肉组织（鼻息肉组）中IL-4、IL-5、IL-6及IL-8的浓度,同时用免疫组织化学法观察其表达,以22例行鼻中隔手术患者中鼻甲黏膜作为对照（对照组）。结果：鼻息肉组IL-5及IL-8水平均明显高于对照组（均P〈0．01）;而IL-6在两组间差异无统计学意义（P〉0．05）;IL-4在变应原皮试阳性组明显增加,与对照组比较P〈0．05。IL-4主要表达于息肉组织内炎性细胞,多为淋巴细胞或浆细胞;IL-5主要表达于鼻息肉组织中嗜酸粒细胞和淋巴细胞;IL-6、IL-8主要表达于息肉上皮层及息肉组织中的炎性细胞,皮试阳性组和阴性组间无明显区别。结论：IL-5及IL-8在所有鼻息肉组织中具有一定作用,而IL-4仅在变应原皮试阳性息肉中具有一定意义,IL-6在鼻息肉组织中无明显作用。     

转化生长因子β1白细胞介素-6及11和17在变应性鼻炎患者鼻黏膜中的表达

目的：探讨转化生长因子β1（TGF-β1），白细胞介素（IL）-6、11和17在变应性鼻炎患者鼻黏膜中的表达及意义。方法：采用酶联免疫吸附试验定量检测19例变应性鼻炎患者（变应性鼻炎组）下鼻甲黏膜和21例行鼻中隔偏曲矫正术的非变应性鼻炎患者（对照组）下鼻甲黏膜组织中TGF-β1，IL-6、11和17的蛋白表达量。结果：①变应性鼻炎组的TGF-β1蛋白表达量显著高于对照组（P〈0．01）；②IL-6、11和17的蛋白表达量在两组间差异无统计学意义（均P〉0．05）；③TGF-β1，IL-6、11和17的蛋白表达量在并发哮喘和不并发哮喘的变应性鼻炎患者间的表达差异无统计学意义（均P〉0．05）。结论：TGF-β1可能在变应性鼻炎的组织结构重塑中起作用，而IL-6、11和17可能在此过程中无明显作用，这可能是变应性鼻炎和哮喘组织结构重塑差异的分子基础之一。     

变应性因素及变应性鼻炎与慢性鼻-鼻窦炎鼻息肉的相关性探讨

目的：探讨变应性因素及变应性鼻炎（AR）与慢性鼻-鼻窦炎鼻息肉的临床相关性。方法：将200例研究对象分为A、B组,A组诊断为AR（110例）,B组诊断为慢性鼻-鼻窦炎鼻息肉（90例）,通过欧蒙印迹法定量检测血清sIgE浓度并观察慢性鼻-鼻窦炎鼻息肉手术治疗后的复发率、AR并发慢性鼻-鼻窦炎鼻息肉的发生率。结果：A组sIgE总阳性率为89.09%,B组sIgE总阳性率为74.44%。B组中sIgE阳性者术后复发率为58.21%,sIgE阴性者术后复发率为8.70%。A组41例（37.27%）并发慢性鼻-鼻窦炎鼻息肉,血清sIgE阳性率为97.56%;69例（62.73%）未并发慢性鼻-鼻窦炎鼻息肉,血清sIgE阳性率为79.71%;组内slgE阳性率比较差异有统计学意义（χ2=6.96,P〈0.01）。结论：变应性因素及AR与慢性鼻-鼻窦炎鼻息肉的发生有一定的相关性,提示避免接触变应原、合理治疗AR能够有效控制慢性鼻-鼻窦炎鼻息肉的复发率。