全身应用激素对鼻息肉组织中嗜酸性粒细胞浸润和转化生长因子β1表达的影响

目的观察全身应用激素对鼻息肉组织中转化生长因子β1(TGFβ1)表达和嗜酸性粒细胞浸润的影响.方法采用免疫组化SP法,检测在激素治疗前后TGFβ1在鼻息肉组织中的表达,运用HPIAS-1000高分辨率图像分析系统分别对激素治疗前后鼻息肉组织的黏膜上皮细胞、腺上皮细胞、血管内皮细胞、嗜酸性粒细胞、基质及黏膜下浸润阳性细胞进行光密度测定.结果激素治疗前,TGFβ1在鼻息肉黏膜上皮细胞、腺上皮细胞、血管内皮细胞、部分嗜酸性粒细胞、基质及黏膜下浸润炎性细胞均有表达,且多数为强阳性和阳性;激素治疗后,TGFβ1在黏膜上皮、基质及黏膜下浸润阳性细胞表达显著降低,其平均光密度值与治疗前比较,差异有显著性意义(P＜0.05);治疗后嗜酸性粒细胞数减少,TGFβ1在嗜酸性粒细胞的表达率下降,与治疗前比较,差异均有显著性意义(均P＜0.05).结论激素可能通过降低鼻息肉组织中嗜酸性粒细胞的浸润和TGFβ1含量而达到治疗鼻息肉的作用.     

糖皮质激素对鼻息肉组织中细胞因子Eotaxin、Eotaxin-2表达的影响

目的：观察嗜酸粒细胞趋化蛋白（Eotaxin）、嗜酸粒细胞趋化蛋白-2（Eotaxin-2）在鼻息肉组织中的表达,研究Eotaxin、Eotaxin-2对嗜酸粒细胞的趋化作用,探讨糖皮质激素（地塞米松）治疗对Eotaxin、Eotaxin-2表达的影响。方法：采用免疫组织化学SP法检测Eotaxin、Eotaxin-2在鼻息肉组织中的表达,HPIAL-2000型彩色全自动图像分析仪进行阳性细胞吸收度测定,对糖皮质激素治疗前后的差异进行分析。结果：①Eotaxin在鼻息肉黏膜上皮细胞、血管内皮细胞、腺上皮细胞、黏膜下浸润炎性细胞均有阳性表达;糖皮质激素治疗后Eotaxin在黏膜上皮细胞、黏膜下浸润炎性细胞及血管内皮细胞中的表达显著降低,治疗前后差异有统计学意义（P〈0．05）;治疗后嗜酸粒细胞数减少,治疗前后差异有统计学意义（P〈0．05）。②Eotaxin-2在鼻息肉黏膜上皮细胞、血管内皮细胞、腺上皮细胞、黏膜下浸润炎性细胞中均有阳性表达;激素治疗后,Eotaxin-2在黏膜上皮细胞显著降低,治疗前后差异有统计学意义（P〈0．01）;在黏膜下浸润炎性细胞中表达显著降低,治疗前后差异有统计学意义（P〈0．05）。Eotaxin-2在鼻息肉黏膜上皮细胞中表达最高,糖皮质激素治疗后对Eotaxin-2在黏膜上皮细胞中的表达影响最大。结论：①Eotaxin和Eotaxin-2在鼻息肉组织中均有高表达;②通过下调鼻息肉黏膜上皮细胞、炎性细胞和血管内皮细胞Eotaxin蛋白的表达,减少了嗜酸粒细胞募集和活化,从而减轻鼻息肉的嗜酸粒细胞性炎症反应程度,是糖皮质激素控制鼻息肉症状的重要途径之一。     

嗜酸性粒细胞与慢性鼻-鼻窦炎伴鼻息肉的相关性研究进展

慢性鼻窦炎（chronic rhinosinusitis,CRS）是鼻腔黏膜和鼻窦黏膜的慢性炎性疾病,根据有无鼻息肉可分为慢性鼻-鼻窦炎伴鼻息肉（chronic rhinosinusitis with nasal polyps,CRSwNP）和慢性鼻-鼻窦炎（chronic rhinosinusitis without nasal polyps,CRSsNP）。鼻息肉组织常见有嗜酸性粒细胞(eosinophils,EOS) 浸润增多,根据嗜酸性粒细胞的浸润程度可将CRSwNP分为两个亚型：嗜酸粒细胞型慢性鼻窦炎伴鼻息肉(eosinophilic chronic rhinosinusitis with nasal polyps, ECRSwNP)和非嗜酸粒细胞型慢性鼻窦炎伴鼻息肉 (nonesinophilc chronic rhinosinusitis with nasal polyps,nonECRSwNP);将慢性鼻窦炎分为：嗜酸粒细胞型慢性鼻窦炎（eosinophilic chronic rhinosinusitis, ECRS)和非嗜酸粒细胞型慢性鼻窦炎(non eosinophilic,NECRS)。嗜酸性粒细胞在鼻息肉形成、发展机制中的作用多年来一直备受学者们关注。随着研究的不断深入,嗜酸性粒细胞在鼻窦炎鼻息肉炎症趋化、息肉形成、分型和预后中的作用得到越来越多的重视。     

鼻息肉手术疗效及术后鼻腔黏膜转归与嗜酸性粒细胞局部浸润的相关性探讨

目的探讨嗜酸性粒细胞局部浸润程度对鼻息肉手术疗效及术后鼻腔黏膜转归的影响。方法鼻息肉患者50例，分别于鼻内镜术中取息肉组织标本及术后恢复期取上颌窦口周边水肿黏膜标本备检；另取20例正常志愿者中鼻甲黏膜组织标本作为对照。Chromotrope 2R特染法检测标本嗜酸性粒细胞浸润程度，分析评价其浸润程度对术后鼻腔黏膜恢复过程的影响。结果鼻息肉组织中嗜酸性粒细胞浸润程度显著高于中鼻甲黏膜组织（P〈0.01），且随时间进程而呈现不同的变化规律。嗜酸性粒细胞浸润程度越明显，鼻腔黏膜恢复过程越慢，鼻息肉复发越快。结论局部黏膜的嗜酸性粒细胞浸润在鼻息肉的形成和发展中起重要作用，可能延迟术后鼻窦、鼻腔黏膜的上皮化进程而影响手术疗效。     

Eotaxin-3在鼻息肉中的表达及作用

目的探讨嗜酸性粒细胞趋化因子(Eotaxin-3)mRNA在鼻息肉中的表达及作用。方法选取12例鼻息肉患者和8例单纯鼻中隔偏曲患者的下鼻甲黏膜作为对照,使用实时定量逆转录PCR进行检测,比较息肉和下鼻甲黏膜中的Eotaxin-3的表达情况。结果在所有鼻息肉及对照组中,均检测到Eotaxin-3 mRNA的表达。鼻息肉及对照组中Eotaxin-3 mRNA的相对表达量分别为22.91±6.66和1.3 7±0.4 8。鼻息肉组中Eotaxin-3的表达要远远高于对照组,差异具有统计学意义(P<0.0 1)。结论 Eotaxin-3可能在鼻息肉的发生发展过程中起到重要作用,Eotaxin-3的高表达可能最终导致了息肉的形成和生长。     

鼻息肉组织及上皮细胞的形态学特征与嗜酸粒细胞阳离子蛋白的表达

目的:研究鼻息肉组织及其上皮细胞的形态学特征,检测嗜酸粒细胞阳离子蛋白(ECP)在其中的表达,探讨其发病机制及病理特点、ECP的作用。方法:慢性鼻-鼻窦炎不伴鼻息肉(鼻窦炎组)5例,慢性鼻-鼻窦炎伴鼻息肉(鼻息肉组)5例,正常下鼻甲黏膜(对照组)5例,标本均分成2份,一份放入4%的戊二醛液中固定,常规电镜制片;另一份放入10%甲醛中固定,石蜡包埋行ECP原位杂交检测。结果:电镜下见鼻息肉组黏膜上皮排列紊乱,基底膜增厚,纤毛排列不整齐,倒伏,其中基底层有脱颗粒现象,鼻窦炎组上皮层破坏、基底膜水肿;对照组上皮层连续,基底层排列整齐。鼻窦炎组、鼻息肉组ECP阳性表达于上皮层、黏膜下层及血管周,呈棕褐色,但鼻窦炎组表达较鼻息肉组低。结论:鼻息肉组织及上皮细胞内有活化的嗜酸粒细胞,脱颗粒现象,鼻息肉组织中ECP高表达,说明鼻窦炎和(或)鼻息肉组织中有活跃的炎症反应,引起组织上皮损伤和脱落,最终形成鼻息肉。     

鼻息肉组织及上皮细胞的形态学特征与嗜酸粒细胞阳离子蛋白韵表达

目的：研究鼻息肉组织及其上皮细胞的形态学特征，检测嗜酸粒细胞阳离子蛋白（ECP）在其中的表达，探讨其发病机制及病理特点、ECP的作用。方法：慢性鼻-鼻窦炎不伴鼻息肉（鼻窦炎组）5例，慢性鼻-鼻窦炎伴鼻息肉（鼻息肉组）5例，正常下鼻甲黏膜（对照组）5例，标本均分成2份，一份放入4％的戊二醛液中固定，常规电镜制片；另一份放入10％甲醛中固定，石蜡包埋行ECP原位杂交检测。结果：电镜下见鼻息肉组黏膜上皮排列紊乱，基底膜增厚，纤毛排列不整齐，倒伏，其中基底层有脱颗粒现象，鼻窦炎组上皮层破坏、基底膜水肿；对照组上皮层连续，基底层排列整齐。鼻窦炎组、鼻息肉组ECP阳性表达于上皮层、黏膜下层及血管周，呈棕褐色，但鼻窦炎组表达较鼻息肉组低。结论：鼻息肉组织及上皮细胞内有活化的嗜酸粒细胞，脱颗粒现象，鼻息肉组织中ECP高表达，说明鼻窦炎和（或）鼻息肉组织中有活跃的炎症反应，引起组织上皮损伤和脱落，最终形成鼻息肉。     

嗜酸性粒细胞浸润对鼻息肉术后鼻腔黏膜转归及疗效的影响

目的：探讨嗜酸性粒细胞（eosinophils, EOS）浸润对鼻息肉术后鼻腔黏膜转归及疗效影响的因素。方法：对于50例鼻息肉患者术中及部分术后复发的鼻息肉组织和上颌窦口周边水肿组织采用Chromotrope 2R特染,检测以上标本中嗜酸性粒细胞在功能性鼻窦内窥镜术后术腔黏膜恢复过程中的表达水平,并进行相关分析。结果：鼻息肉组织中EOS水平明显高于中鼻甲黏膜组织,且随时间呈现不同的变化规律（P＜0.01）;EOS浸润程度越深,鼻腔黏膜恢复越慢,鼻息肉复发越快。结论：EOS浸润在鼻息肉的形成和发展中起重要作用,提示其可能参与延迟鼻窦、鼻腔黏膜上皮化的进程,可作为疗效判断的指标之一。     

Survivin在鼻息肉组织中的表达及与嗜酸性粒细胞浸润相关性的研究

目的研究生存素（Survivin）在鼻息肉组织中的表达及其与嗜酸性粒细胞浸润的相关性,探讨Survivin在鼻息肉发病过程中的作用。方法收集28例鼻息肉组织（鼻息肉组）和12例正常下鼻甲组织（对照组）,用HE染色法观察组织中的嗜酸性粒细胞浸润情况,免疫组化法检测组织中Survivin的表达。结果①HE染色显示鼻息肉组嗜酸性粒细胞浸润显著增加。②免疫组织化学染色显示Survivin免疫阳性细胞数及着色强度均明显高于对照组,图像分析显示,鼻息肉组Survivin的积分光密度（IOD,103/HP）为50.21±6.32,与对照组5.67±0.58相比有统计学意义（P〈0.05）。③Spearman等级相关分析显示,鼻息肉中Survivin表达与嗜酸性粒细胞浸润表达密切相关（r=0.673,P〈0.01）。结论鼻息肉组织中Survivin表达、嗜酸性粒细胞浸润均上调,且二者有协同表达关系。鼻息肉可能是通过凋亡抑制基因Survivin使炎性细胞凋亡受到抑制,从而促进炎性细胞主要是嗜酸性粒细胞浸润生长,导致慢性炎症反应。     

鼻息肉组织中抗原递呈细胞对嗜酸性粒细胞浸润的病理学意义

目的探讨鼻息肉组织中抗原递呈细胞对嗜酸性粒细胞浸润的意义及与鼻息肉发病机制的关系.方法对10例正常鼻粘膜和14例鼻息肉组织进行免疫组织化学和组织病理学染色观察.结果鼻息肉组织中嗜酸性粒细胞和CD68表达阳性的巨噬细胞与正常鼻粘膜相比均显著增加(P<0.05).结论抗原递呈细胞-巨噬细胞在鼻息肉组织中的浸润可能有重要作用,而且以嗜酸性粒细胞为主的炎性效应细胞的积聚与介质释放所导致的鼻粘膜慢性炎症损伤可能是鼻息肉形成的重要原因.     

Significance and expression of transforming growth factor beta in human nasal polyp tissue]

OBJECTIVE: To explore the pathogenesis of nasal polyposis and the expression of transforming growth factor beta (TGF-beta) in human inflammatory nasal polyps. METHODS: TGF-beta 1-3 in nasal polyp tissues and inferior turbinate mucosa of twenty-five polyposis patients were detected with immunohistochemistry alkaline phosphatase and anti-alkaline phosphatase (APAAP) method. The inferior turbinate mucosa of eight healthy volunteers were selected as control. Six polyp tissues were estimated with double immunolabeling and Western-blot analysis to compare the characterization of the TGF-beta isoforms expression and the proportion of macrophages and eosinophils in nasal polyp tissues. RESULTS: The expression of TGF-beta 1-3 in nasal polyps was significantly higher than that in nasal mucosa and indetecable in nasal mucosa from healthy volunteers; TGF-beta 1 was the main isoform detected in nasal polyps; TGF-beta positively was accompanied by numerous macrophage and eosinophil infiltration. CONCLUSIONS: TGF-beta mainly TGF-beta 1 is strongly expressed in nasal polyps and its mucosa, where it could be produced by macrophages and eosinophils. TGF-beta could induce modification of epithelium and connective tissue and therefore be involved in the pathogenesis of nasal polyposis.     

鼻息肉中CD34的表达及其与嗜酸粒细胞浸润的关系

目的 探讨CD34在人鼻息肉组织中的表达及其与嗜酸粒细胞浸润的关系。方法 采用HE和免疫组化ElivisionPlus二步法，检测30例正常下鼻甲，60例鼻息肉组织中CD34蛋白的表达情况，并对CD34阻性血管进行微血管（MVD））计数，了解微血管的分布及嗜酸粒细胞的浸润情况。结果 鼻息肉组织中CD34阳性表达广泛，正常下鼻甲组织中CD34呈散在的弱阳性表达；鼻息肉组织中MVD明显高于下鼻甲组织中MVD（P〈0．01），与嗜酸粒细胞的浸润具有正相关性。结论 CD34蛋白有可能介导嗜酸粒细胞的浸润，加重对鼻黏膜的损害。     

STAT6在鼻息肉组织中的表达及其与嗜酸粒细胞浸润的关系

目的：研究信号转导和转录激活因子6（STAT6）在鼻息肉组织中的表达及其对嗜酸粒细胞（EOS）浸润聚集的作用,探讨其在鼻息肉发生中的可能作用。方法：选取符合纳入标准的鼻息肉患者手术切除标本（鼻息肉组）30例和同期单纯行鼻中隔偏曲矫正术中切除的下鼻甲组织（对照组）10例。采用免疫组织化学SP法检测2组下鼻甲黏膜中STAT6的表达。应用SPSS13.0软件进行统计学分析。结果：STAT6和EOS在鼻息肉组织中的表达明显高于下鼻甲,差异有统计学意义（P〈0.05）。STAT6阳性细胞主要集中于鼻息肉的上皮细胞、腺体细胞和组织中浸润的炎性细胞的细胞质中。鼻息肉组中STAT6的表达与EOS浸润程度一致（P〈0.01）。结论：STAT6在鼻息肉组织中的高表达及其对EOS浸润聚集的作用,可能与鼻息肉的发生和发展关系密切。     

鼻息肉中碳酸酐酶IX表达与嗜酸细胞浸润相关性分析

目的研究碳酸酐酶IX（carbonic anhydrase IX,CAIX）在鼻息肉组织中表达及其与嗜酸细胞（eosinophils,Eos）浸润的相关性,探讨CAIX在鼻息肉发病中的作用。方法收集28例鼻息肉组织（鼻息肉组）和12例正常下鼻甲组织（对照组）,HE染色观察Eos浸润情况,免疫组化检测CAIX的表达。结果与对照组比较,鼻息肉组Eos浸润显著增加,CAIX免疫阳性细胞数及着色强度明显增高。图像分析显示,鼻息肉组CAIX的积分光密度（103/HP）为26.87±4.60,与对照组3.25±1.20相比,有显著性差异（P〈0.05）;Spearman等级相关分析显示,鼻息肉中CAIX表达与Eos浸润表达密切相关（r=0.632,P〈0.01）。结论鼻息肉组织中CAIX表达、Eos浸润均上调,二者有协同表达关系,说明鼻息肉组织中存在缺氧及缺氧适应现象,CAIX表达上调,从而使细胞适应缺氧微环境,保证缺氧区域细胞的持续生长和增殖,促进Eos浸润生长,导致一种慢性炎症反应。     

VCAM-1 and eosinophilia in diffuse sino-nasal polyps

The objective of our study was to investigate: the expression of vascular cell adhesion molecule-1 (VCAM-1) in diffuse sino-nasal polyps; the relation between VCAM-1 and selective eosinophilia in diffuse sino-nasal polyps; the effect of eosinophilia and VCAM-1 expression on recurrence of diffuse sino-nasal polyps following treatment. Fifty patients with diffuse sino-nasal polyps were included in the study. Biopsies were taken from the polyps and the inferior turbinate mucosa of each patient and were studied by immunohistochemical staining for detection of VCAM-1 expression on the blood vessels, as well as by hematoxylin and eosin (H&E) staining for detection of eosinophils. The percentage of blood vessels expressing VCAM-1 and the number of eosinophils in the polyps were detected and correlated and then compared to the corresponding numbers in the inferior turbinates. All patients were treated by endoscopic ethmoidectomies followed by local steroids for 1 year. Recurrence of polyps was monitored during the post-operative follow-up period. The quantitative expression of VCAM-1 and number of infiltrating eosinophils were compared in patients who developed recurrent polyps and those who did not. VCAM-1 was expressed in the polyps but not significantly higher than in the inferior turbinates of the patients or the controls. Eosinophils were significantly higher in the polyps compared to the inferior turbinates. No correlation was found between the expression of the VCAM-1 and the number of eosinophils. VCAM-1 expression was significantly higher in patients developing recurrent polyps. No significant difference was found in the number of infiltrating eosinophils between patients developing and those not developing recurrent polyps. VCAM-1 is expressed in polyps but not significantly higher than its expression in the inferior turbinate mucosa. VCAM-1 expression in diffuse sino-nasal polyps cannot on its own explain the selective eosinophilia detected in this disease. High VCAM-1 expression in diffuse sino-nasal polyps may be an indicator of a higher probability of polyps recurrence. Degree of eosinophilic infiltration cannot be taken as such an indicator. The study was performed in the Faculty of Medicine, University of Alexandria. It was supported by a research fund from the University. The study was approved by the research committee of the University of Alexandria which is also concerned with ethical approvals.     

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.     

水通道蛋白-1在鼻息肉中的表达及其调节机制

目的：研究水通道蛋白-1(aquaporin1, AQP1)在鼻息肉组织中的表达,探讨其 与鼻息肉水肿形成及发展的关系。方法：取鼻中隔偏曲矫正术患者下鼻甲黏膜30例和鼻息肉组织60例。鼻息肉组Ⅱ型1期10例, 2期15例, 3期25例,Ⅲ型10例。采用免疫组织化学检测AQP1在不同类型及不同临床分期鼻息肉和下鼻甲黏膜组织中的表达及在不同类型鼻息肉组织中的表达。结果：（1）鼻息肉上皮层AQP1阳性细胞数显著高于下鼻甲黏膜(Ｐ＜0 01); 不同分型分期鼻息肉上皮层AQP1的阳性细胞数又有差异,Ⅱ型3期和Ⅲ型鼻息肉显著低于Ⅱ型1期鼻息肉(Ｐ＜0 01); 而在鼻息肉血管内皮及腺体细胞中的AQP1的表达明显高于下鼻甲(Ｐ＜0 01); （2）Ⅱ型3期和Ⅲ型鼻息肉血管内皮中AQP1阳性细胞数显著高于Ⅱ型1期鼻息肉和下鼻甲黏膜上皮下组织(Ｐ＜0 01)。结论：AQP1在鼻息肉组织中的异常表达可能与鼻息肉的发生和发展密切相关, 具体机制有待进一步研究。     

Expression of cell proliferation and apoptosis gene associated protein on nasal polyps and its significance]

OBJECTIVE: To further understand the pathogenic mechanism of nasal polyps, namely the cells proliferation and apoptosis in nasal polyps tissue. METHODS: The proliferation cell nuclear antigen (PCNA), apoptosis associated gene protein (Bcl-2, Bax) were determined in 26 tissue samples of nasal polyps and 14 controls from normal inferior turbinates respectively. RESULTS: (1) The positive expression e of PCNA, Bcl-2 and Bax were significantly higher in epithelium of nasal polyps than the controls, and the expression rate of Bcl-2/Bax, however, tended equipoise. (2) The expression of Bcl-2 were significantly stronger than Bax in glands, eosinophils of nasal polyps tissue, and there were not significant differences in inferior turbinates. CONCLUSION: There is strongly proliferation activity in the epithelium of nasal polyps, and expression imbalance of Bcl-2/Bax may be one of the important factors of eosinophilia in nasal polyps tissue.