Decreased PLUNC expression in nasal polyps is associated with multibacterial colonization in chronic rhinosinusitis patients

PLUNC (palate, lung, and nasal epithelium clone) is an epithelium-secreted protein that plays a crucial role in the host’s defense against bacterial infection. The function of PLUNC in the sinus remains poorly understood. To examine whether the expression levels of PLUNC could serve as a predictive outcome biomarker for patients with CRSwNP and bacterial colonization, we investigated the association of PLUNC expression levels with bacterial colonization in the sinuses. A total of 174 patients who underwent sinus surgery for chronic rhinosinusitis with nasal polyps (CRSwNP) were enrolled in this study. The tissue samples obtained from patients were examined using preoperative sinus computed tomography (CT) scans, postoperative bacterial cultures, and nasal polyp examinations. PLUNC mRNA and protein expression were quantified using RT-PCR and immunohistochemistry. We identified that decreased PLUNC expression is associated with multibacterial colonization (P = 0.0001), specifically those mediated by Staphyloccocus aureus (P = 0.037) and Pseudomonas aeruginosa (P = 0.002). The patients who required repeated sinus surgeries for recurrent or persistent sinusitis also presented much lower PLUNC expression than those who did not require repeated sinus surgery (P = 0.001). However, gender, age, and CT scores were not associated with PLUNC expression. These results suggest that reduced PLUNC expression is associated with bacterial colonization as well as treatment outcome in CRSwNP patients. Investigation of the association between PLUNC expressions and chronic rhinosinusitis may lead to the development of a novel biomarker for treatment outcome in CRSwNP patients.     

天然免疫蛋白PLUNC在鼻息肉中的表达及与鼻息肉临床特征的关联性

目的：探讨天然免疫蛋白腭、肺、鼻上皮克隆（PLUNC）在鼻息肉组织中的表达情况,分析PLUNC蛋白浓度与鼻息肉大小（鼻内镜记分）和手术后复发的关联性。方法：采用免疫组织化学和实时定量PCR检测鼻息肉组（28例鼻息肉患者,其中13例为术后复发患者）和对照组（16例钩突黏膜对照）PLUNC的组织染色定位和mRNA的表达情况,同时采用ELISA检测初发和复发鼻息肉组织中PLUNC的蛋白浓度差异,评估PLUNC蛋白浓度与息肉大小、鼻塞、流涕症状记分的相关性。结果：鼻息肉组织中PLUNC主要定位在黏膜上皮和腺体,染色强度记分显著低于对照的钩突组织（P〈0．01）;PLUNCmRNA表达水平也显著低于对照的钩突组织（P〈0．01）。初发和复发鼻息肉组织中PLUNC蛋白OD值分别为0．33±0．11和0．15±0．05,差异有统计学意义（P〈0．01）。小型和大型鼻息肉PLUNC蛋白OD值分别为0．32±0．14和0．19±0．07,差异有统计学意义（P〈0．05）。鼻息肉组织中PLUNC蛋白浓度与鼻塞和流涕记分存在显著负相关（r=-0．51和r=-0．57,P〈0．01）。结论：PLUNC的表达降低提示鼻息肉的发生可能与天然免疫反应的减弱有关,因此,上调天然免疫分子如PLUNC等的表达可作为干预鼻息肉发病的一个新策略。     

慢性鼻-鼻窦炎鼻息肉与正常鼻黏膜差异蛋白质的检测及其意义

目的采用蛋白质组学技术筛选慢性鼻-鼻窦炎、鼻息肉和正常鼻黏膜组织之间差异表达的蛋白质,初步鉴定出慢性鼻-鼻窦炎和鼻息肉的候选蛋白质标记物。方法应用固相pH4~7胶条行双向凝胶电泳,胶体考马斯亮蓝染色后,扫描2-DE胶,应用PDquest图像分析软件比较慢性鼻-鼻窦炎、鼻息肉和正常鼻黏膜组织2-DE图谱,得到三组之间差异表达的蛋白质点。经MALDI-TOF-MS鉴定后获得这些差异表达蛋白质的肽质量指纹图谱,用Mascot软件查询NCBInr和SWISS-PROT数据库,得出被测蛋白质的鉴定结果。结果所获双向凝胶电泳图谱分辨率高、重复性好。测得鼻息肉、慢性鼻-鼻窦炎及正常鼻黏膜组织的蛋白质平均斑点数分别为1020±40、1112±10和1008±25;平均匹配率分别为(93±2)%、(95±1)%和(90±3)%。三组之间共计有13个明显差异表达的蛋白质点。初步筛选出角蛋白8和阿朴脂蛋白AI作为鼻息肉的候选标志物,以及PLUNC蛋白、超氧化物歧化酶、自然杀伤细胞促进因子B、垂体腺苷酸环化酶激活肽为慢性鼻-鼻窦炎的候选标志物。结论用蛋白质组学技术能高通量筛选慢性鼻-鼻窦炎、鼻息肉和正常鼻黏膜间存在的差异表达蛋白质,这将为慢性鼻-鼻窦炎、鼻息肉分类、分型分期和预后判断标准寻找新的客观参考指标。     

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.     

溶菌酶和乳铁蛋白在慢性鼻窦炎钩突粘膜中的表达

目的 了解钩突在局部防御慢性炎症过程中的作用。方法 采用免疫组化ＡＢＣ法，检测溶菌酶（ＬＺ）和乳铁蛋白（ＬＦ）在１７侧健康和７０侧慢性鼻窦炎患者（分为单纯炎症组和合并鼻息肉组）钩突粘膜中的表达情况。结果 ①ＬＺ在单纯炎症组钩突粘膜杯状细胞中表达较健康对照组加强（Ｐ〈０．０５）；ＬＦ在健康和慢性鼻窦炎钩突杯状细胞中常为阴性表达；②ＬＺ在健康和慢性鼻窦炎钩突粘膜腺体的浆液性和粘液性细胞中均有表达；ＬＦ     

EOS与COX-2在阿司匹林三联征患者鼻息肉组织中的表达及意义

目的:探讨嗜酸粒细胞(EOS)的聚集和COX-2在阿司匹林三联征(ST)发病过程中的调控作用。方法:取94例鼻内镜手术患者鼻息肉组织,其中ST患者34例(ST组),慢性鼻窦炎鼻息肉伴哮喘患者30例(ATA组),慢性鼻窦炎鼻息肉患者30例(对照组),应用苏木精-伊红染色及免疫组织化学SP法检测EOS的分布及COX-2的表达,并经统计学分析EOS、COX-2的表达和分布与临床病理和发病机制的关联。结果:EOS在3组患者鼻息肉组织中均大量浸润,EOS计数均数分别为80.02±6.11、76.62±5.22、65.97±4.78,ST组、ATA组分别与对照组比较差异均有统计学意义(均P<0.05),而ST组与ATA组比较差异无统计学意义(P>0.05)。COX-2在鼻息肉组织中主要表达于黏膜下腺体、腺上皮细胞、上皮细胞、血管内皮细胞及间质中的EOS,阳性细胞计数分别为88.13±6.26、89.46±5.97、91.22±4.11,ST组与对照组表达差异有统计学意义(P<0.05);ATA组表达与对照组比较差异无统计学意义(P>0.05);ST组与ATA组比较差异无统计学意义(P>0.05)。结论:EOS浸润程度不同可能是ST患者接触非甾体抗炎药后发生特有临床表现的炎症基础,COX-2在ST患者息肉组织中表达的差异可能与花生四烯酸代谢途径的转换及鼻息肉的形成有关。     

TLR2和TLR4在慢性鼻窦炎鼻息肉中的表达及临床意义

目的检测Toll样受体2(toll-like receptor 2,TLR2)和Toll样受体4(toll-like receptor 4,TLR4)蛋白在慢性鼻窦炎鼻息肉黏膜组织中的表达,并探讨其在鼻窦炎鼻息肉发病机制中的作用。方法采用免疫组织化学技术检测62例鼻窦炎鼻息肉黏膜组织中TLR2和TLR4蛋白的表达和分布,同期选取5例正常筛窦黏膜组织进行对照。按照1997年海口制定的"慢性鼻窦炎鼻息肉临床分型分期及鼻内镜下鼻窦手术疗效评定标准"将其分组,比较各组间TLR2和TLR4表达程度的差异。结果①TLR2、TLR4主要表达在鼻腔黏膜上皮细胞、固有层炎性细胞及黏膜下层腺体的胞浆和胞膜上。②慢性鼻窦炎鼻息肉各型各期均较对照组高;并且随着分型的升高,TLR2、TLR4的表达量也随之增加,差异具有统计学意义(P<0.05)。结论 TLR2和TLR4在鼻窦炎鼻息肉中的表达可能与鼻窦炎鼻息肉的发病机制存在着一定的相互关联,TLR在该机制中可能扮演重要角色。     

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。     

LL-37和IL-8在慢性鼻窦炎鼻息肉组织中的表达及意义

目的:研究人源抗菌肽LL-37和IL-8在慢性鼻窦炎鼻息肉组织中的表达。方法:采用半定量RT-PCR和免疫组织化学方法检测31例慢性鼻窦炎息肉组织中LL-37和IL-8的表达,并以11例慢性鼻炎下鼻甲组织作对照。结果:LL-37和IL-8 mRNA在所有息肉组织和下鼻甲组织中均呈阳性表达,二者在息肉组织中的表达均明显高于下鼻甲组织(均P<0.01),且在息肉组织中的表达呈正相关(P<0.01);LL-37与IL-8蛋白在鼻息肉组织中的阳性表达率均明显高于下鼻甲组织(均P<0.01),二者在息肉组织中的阳性表达率呈正相关(P<0.01)。结论:LL-37和IL-8可能在慢性鼻窦炎的发病中发挥一定作用;除天然免疫作用外,LL-37还可能通过增强获得性免疫提高机体的抗感染功能。     

支原体感染与慢性鼻-鼻窦炎鼻息肉患者糖皮质激素治疗敏感性的关系探讨

目的探讨支原体感染与慢性鼻-鼻窦炎鼻息肉患者糖皮质激素治疗敏感性的关系。方法96例慢性鼻-鼻窦炎鼻息肉患者给予经鼻使用丙酸氟替卡松治疗,根据治疗后症状缓解程度,筛选出治疗敏感者30例和不敏感者18例,以单纯性鼻塞患者20例为对照组,应用单克隆抗体免疫荧光法分别检测其鼻腔鼻窦内支原体的感染率。结果激素治疗敏感组支原体感染率为43.3%,激素不敏感组支原体感染率为83.3%,对照组支原体感染率为10%;敏感组和不敏感组比较支原体感染率差异有显著性（P〈0.05）,且敏感组和不敏感组支原体感染率与对照组比较差异均有显著性（P〈0.05）。结论支原体感染在慢性鼻-鼻窦炎鼻息肉的发生发展过程中可能起着重要作用,且与慢性鼻-鼻窦炎鼻息肉患者糖皮质激素治疗敏感性密切相关。     

阿奇霉素对慢性鼻-鼻窦炎患者术腔黏膜中NF-kBp65IL-8表达的影响

目的 观察阿奇霉素对慢性鼻-鼻窦炎患者术腔黏膜中NF-kBp65、IL-8表达的影响,探讨阿奇霉素治疗术腔慢性炎症的机制。方法 将45例慢性鼻-鼻窦炎术后2周的患者随机分成阿奇霉素组、头孢菌素组和对照组进行随访治疗,所有患者均应用布地奈德喷鼻、生理盐水冲洗术腔,阿奇霉素组加用阿奇霉素500mg口服,每日1次;头孢菌素组加用头孢菌素500mg口服,每日1次;对照组继续同前治疗,连续3周后,取术腔病变黏膜作为实验标本,应用免疫组织化学PV-6000二步法检测各组治疗前后及三组间术腔黏膜上皮细胞、炎性细胞中NF-kBp65和IL-8表达的情况,计数阳性细胞数。结果 慢性鼻-鼻窦炎患者术腔黏膜呈慢性炎症表现,NF-kBp65主要表达在术腔黏膜的黏膜上皮细胞、炎性细胞的胞浆和部分胞核。IL-8主要表达在黏膜的上皮细胞、炎性细胞的胞浆。三组治疗后NF-kBp65和IL-8在上皮细胞和炎性细胞中的表达均较治疗前减少(P<0.05);阿奇霉素组治疗后术腔黏膜上皮细胞和炎性细胞中NF-kBp65、IL-8的表达均较头孢菌素组、对照组明显减少(P<0.05);头孢菌素组与对照组治疗后上皮细胞和炎性细胞中NF-kBp65、IL-8的表达无明显差别(P>0.05)。结论 阿奇霉素联合应用布地奈德抑制慢性鼻-鼻窦炎患者术腔黏膜上皮细胞、炎性细胞中NF-kBp65、IL-8的表达,较单独应用布地奈德明显,可能是阿奇霉素治疗慢性炎症的机制之一,对慢性鼻-鼻窦炎患者术腔黏膜慢性炎症的转归具有促进作用。     

老年慢性鼻窦炎患者鼻内镜手术的临床分析

目的探讨鼻内镜手术在老年慢性鼻窦炎、鼻息肉患者中的应用及疗效.方法回顾性分析68例＞60岁的老年慢性鼻窦炎、鼻息肉患者行鼻内镜手术的临床资料.结果随访6～50月,治愈52例(76.5%),好转10例(14.7),无效6例(8.8%),总有效率91.2%.结论鼻内镜手术是治疗老年鼻窦炎、鼻息肉的一个安全、有效方法.     

The role of topical corticosteroids after functional endoscopic sinus surgery for chronic sinusitis and/or nasal polyps

Introduction. The objective was determination of the influence of Fluticasone propionate nasal spray on the recurrence rate of chronic sinusitis and/or nasal polyps after functional endoscopic sinus surgery (FESS) using a randomized double‐blind placebo‐controlled trial. Methods. From 1994 to 1997, 162 patients were included in this trial after FESS for chronic sinusitis and/or nasal polyps. Postoperatively they were treated for 1 year with study medication (double‐blind). Study medication contained Fluticasone propionate nasal spray 400 μg bid, or Fluticasone propionate nasal spray 800 μg bid, or placebo bid. Symptoms (using visual analogue scales) and nasendoscopy findings were scored preoperatively and postoperatively for 1 year. Results. No reduction of the recurrence rate of chronic sinusitis or nasal polyps was found in the patient‐groups using Fluticasone propionate nasal spray. No reduction was found when separate groups were analysed (such as nasal polyps, chronic sinusitis, allergy, no history of FESS or use of topical corticosteroids, or high score at FESS). Conclusion. In this trial no positive influence of Fluticasone propionate nasal spray could be found on the recurrence rate of chronic sinusitis and/or nasal polyps.     

Immunohistochemical localization of eotaxin immunoreactivity in nasal polyps

Eotaxin is a C-C chemokine that acts to selectively induce local accumulation of eosinophils and basophils. Eotaxin is also believed to be involved in the infiltration of eosinophils in the nasal polyps of patients with chronic sinusitis. However, only a few studies on eotaxin in nasal polyps have been performed. In this study, we investigated the localization of eotaxin in human nasal polyps and the identification of eotaxin-positive cells using immunohistochemistry. The distribution of eotaxin immunoreactivity in the nasal polyps of patients with chronic sinusitis was found to almost coincide with the presence of eosinophils. Eotaxin immunoreactivity was also detected in some vascular endothelial cells. These findings suggest that eotaxin is produced by eosinophils and vascular endothelial cells in nasal polyps and is involved in the accumulation of eosinophils in nasal polyps.     

慢性鼻窦炎鼻息肉与变应性因素相关性的探讨

目的 探讨变应性因素在慢性鼻窦炎鼻息肉发病中的作用。方法回顾性分析1882例慢性鼻窦炎鼻息肉患者术前鼻腔分泌物涂片嗜酸粒细胞及变应原皮肤试验检查结果，并将其变应性症状和体征出现的比例与临床分型分期加以比较。结果①1882例慢性鼻窦炎鼻息肉患者中60．4％(1137例)的患者伴有不同程度的变应性症状和体征，25．3％(477例)的患者合并变应性鼻炎，2．1％(39例)的患者合并支气管哮喘；②在Ⅰ型(708例)和Ⅱ型(823例)各分期的患者中，合并变应性鼻炎及支气管哮喘的发生率和嗜酸粒细胞、皮肤变应原试验阳性率以及变应性鼻炎临床症状出现的百分率分别由低到高出现，Ⅱ型3期各项比例最高；③42．2％(795例)的患者变应原皮肤试验阳性，其中94．3％对常年性变应原呈阳性反应；④26．3％(495例)的患者伴有变应性鼻炎的临床症状，其中99．8％(494／495例)为常年性发作；⑤有前期手术史的病例占38．9％(732例)，其中合并变应性鼻炎者占有前期手术史例数的38．3％(280例)，占合并变应性鼻炎患者的58．7％(477例)。结论变应性因素特别是常年性变应性鼻炎与慢性鼻窦炎鼻息肉的病变程度和病变范围有关。同时变应性鼻炎也促进了疾病的复发。     

中药萍芷片对鼻息肉组织中炎性细胞浸润的影响

目的 :观察口服萍芷片对慢性鼻窦炎鼻息肉组织中炎性细胞浸润情况的影响。方法 :将 80例慢性鼻窦炎鼻息肉患者随机分为 2组 :萍芷片组和对照组 ,每组 4 0例。萍芷片组术前口服萍芷片 ,连服 30d ;对照组术前未作任何治疗。将两组所取得的鼻息肉组织标本分别进行苏木精 伊红染色和免疫组化染色 ,显微镜下观察炎性细胞浸润情况。结果 :萍芷片组鼻息肉组织中CD 11b +、CD7+阳性细胞的浸润数明显减少 ,与对照组比较 ,差异有极显著性意义 (均 P <0 .0 1) ,基质水肿减轻 ;而CD 19+阳性细胞浸润数与对照组比较 ,差异无显著性意义 (P >0 .0 5 )。结论 :口服萍芷片可影响慢性鼻窦炎鼻息肉组织中炎性细胞的浸润程度 ,有局部抗炎作用