黏蛋白在鼻息肉及变应性鼻炎中的基因表达水平的研究

目的：探讨5种人黏蛋白基因（MUC2、MUC5AC、MUC5B、MUC18、MUC19）在鼻息肉和变应性鼻炎中的基因表达水平及临床意义。方法：采用RT-PCR及实时荧光定量RT-PCR,检测35例鼻息肉、18例变应性鼻炎患者下鼻甲及18例正常人黏蛋白基因（MUCS）在下鼻甲黏膜上皮的基因表达水平。结果：RT-PCR及实时荧光定量RT-PCR的结果表明,MUC5AC、MUC5B在鼻息肉组和变应性鼻炎组中的表达高于对照组（P〈0.05）,鼻息肉组与变应性鼻炎组及对照组间表达差异均无统计学意义（P〉0.05）。MUC2、MUC18在3组中的表达差异无统计学意义（P〉0.05）。MUC19在变应性鼻炎组中的表达高于鼻息肉组和对照组（P〈0.05或P〈0.01）。结论：MUC5AC和MUC5B在鼻息肉、变应性鼻炎的黏液过度分泌过程中具有重要意义;MUC19在变应性鼻炎的黏液过度分泌过程中也有重要意义,但是对鼻息肉患者的黏液分泌没有明显作用;未发现MUC2、MUC18在变应性鼻炎的黏液过度分泌过程中起明显作用。     

Tenascin在鼻息肉组织中的表达及其临床意义

目的：探讨Tenascin(TN)在鼻息肉组织中的表达和分布特征及其在鼻息肉发生中的可能作用。方法：采用免疫组化链霉菌抗生物素蛋白—过氧化物酶(SP)法检测24例鼻息肉标本(鼻息肉组)和15例慢性肥厚性鼻炎下鼻甲标本(下鼻甲组)中TN的表达，并以5例健康者(对照组)下鼻甲黏膜作对照。结果：鼻息肉组和下鼻甲组黏膜上皮细胞及腺上皮细胞均表达TN；鼻息肉组TN的黏膜上皮阳性细胞表达的吸光度值显著高于下鼻甲组(P＜0．01)；鼻息肉组TN的腺上皮阳性细胞表达的吸光度值显著高于下鼻甲组(P＜0．01)；对照组下鼻甲组织中黏膜上皮及腺体几乎检测不到TN的表达；鼻息肉组腺体TN阳性率明显高于下鼻甲组(P＜0．05)。结论：TN在鼻息肉组织中的高表达与鼻息肉的发生、发展相关；TN在鼻腔内的表达细胞是黏膜上皮细胞和浆液性腺上皮细胞。     

常年性变应性鼻炎患者鼻粘膜中粘蛋白MUC5AC的表达

目的 :探讨粘蛋白 MUC5 AC在常年性变应性鼻炎发病中的意义。方法 :采用 PAS染色和免疫组化 SABC法检测了 2 3例常年性变应性鼻炎患者鼻粘膜中粘蛋白 MUC5 AC的表达。结果 :2 3例变应性鼻炎鼻粘膜组织中 PAS染色均为阳性 ,粘蛋白 MU C5 AC染色阳性率为 85 .2 % ,主要表达在粘膜下腺体上皮的杯状细胞中。结论 :粘蛋白 MUC5 AC在常年性变应性鼻炎的过度分泌过程中具有重要的意义     

常年性变应性鼻炎患者鼻粘膜中粘蛋白MUC5AC的表达

目的：探讨粘蛋白MUC5AC在常年性变应性鼻炎发病中的意义。方法：采用PAS染色和免疫组化SABE法检测了23例常年性变应性鼻炎患者鼻粘膜中粘蛋白MUC5AC的表达。结果：23例变应性鼻炎鼻粘膜组织中PAS染色均为阳性，粘蛋白MUC5AC染色阳性率为85．2％，主要表达在粘膜下腺体上皮的杯状细胞中。结论：粘蛋白MUC5AC在常年性变应性鼻炎的过度分泌过程中具有重要的意义。     

钙激活氯通道和黏蛋白在变应性鼻炎中的表达与意义

目的:探讨人钙激活氯通道1(hCLCA1)和黏蛋白MUC5AC在变应性鼻炎黏液高分泌中的表达水平及临床意义。方法:采用RT-PCR技术和免疫组织化学法,检测20例变应性鼻炎患者(变应性鼻炎组)和7例正常人(对照组)hCLCA1和MUC5AC在下鼻甲黏膜的表达水平。结果:变应性鼻炎组鼻黏膜hCLCA1mRNA表达阳性,而对照组未出现hCLCA1mRNA的表达,两者比较差异有统计学意义(P<0.01);变应性鼻炎组MUC5ACmRNA表达和MUC5AC蛋白表达均较对照组明显增多(均P<0.01);变应性鼻炎组鼻黏膜hCLCA1mRNA表达与MUC5ACmRNA和蛋白表达均呈直线正相关(r=0.752、0.694,均P<0.05)。结论:hCLCA1mRNA表达的上调可能在变应性鼻炎黏液高分泌中起着关键作用,抑制hCLCA1的表达将为变应性鼻炎的治疗提供新的策略。     

下鼻甲黏膜病理及超微结构观察

目的探讨慢性鼻炎下鼻甲黏膜组织病理及超微结构特征性改变。方法收集38例慢性鼻炎病例标本,其中慢性单纯性鼻炎12例;慢性肥厚性鼻炎26例,其中6例行下鼻甲手术。每例患者分别切取下鼻甲黏膜2块依次送病理及超微结构检查。结果病理及超微结构显示下鼻甲黏膜上皮不同程度脱落、间质炎细胞浸润、纤毛结构不同程度缺损等共同特点。慢性单纯性鼻炎间质腺体增生,血管扩张,炎细胞浸润,伴急性炎症者可见中性粒细胞;慢性肥厚性鼻炎间质以淋巴细胞和浆细胞浸润为主,黏膜上皮脱落化生,间质纤维增生;下鼻甲黏膜下手术患者纤毛结构保护较好。结论慢性单纯性鼻炎和慢性肥厚性鼻炎有不同特征性组织病理及超微结构所见,下鼻甲黏膜下手术是治疗慢性肥厚性鼻炎理想手术方式。     

CFTR蛋白在鼻息肉和正常下鼻甲黏膜中的表达

目的:探讨囊性纤维跨膜转运调节因子(CFTR)在鼻息肉发病机制中的作用。方法:采用免疫组织化学SP法检测28例慢性鼻窦炎患者鼻息肉组织(鼻息肉组)和7例正常下鼻甲黏膜(下鼻甲组)中CFTR蛋白的表达情况。结果:①CFTR在上述2组组织均有表达,主要表达于上皮细胞和分泌细胞,并且优势表达于鼻息肉。CFTR在正常下鼻甲黏膜呈较为单一的顶上膜表达,而在鼻息肉中呈顶上膜表达和细胞质表达并存;②鼻息肉组CFTR的黏膜上皮阳性细胞顶上膜表达的强度值(1.921±0.310)显著高于下鼻甲组(0.971±0.214)(P<0.05)。鼻息肉组CFTR的上皮阳性细胞质表达的强度值(2.036±0.439)亦显著高于下鼻甲组(0.550±0.366)(P<0.05)。结论:氯离子通道CFTR蛋白的过度表达和异常表达可能在鼻息肉的发病机制中起重要的作用。     

跨膜蛋白16A在呼吸道黏膜上皮细胞的表达和功能研究

黏液过度分泌是变应性鼻炎、慢性鼻-鼻窦炎、哮喘、慢性阻塞性肺疾病和囊性纤维化等呼吸道炎性疾病的重要特征。杯状细胞化生、黏液纤毛清除功能障碍是导致鼻腔及呼吸道黏液积聚的重要病理改变。新近研究发现，钙激活氯离子通道（calcium-activated chloride channels，CaCCs）的分子结构跨膜蛋白16A（transmembrane protein16A，TMEM16A）与黏液分泌调控有关，不仅表现在介导电解质跨上皮转运及水合作用，还参与黏液中黏蛋白5AC的分泌调节。本文介 绍TMEM16A在呼吸道黏膜上皮的表达和功能的研究进展。     

水通道蛋白-5在人鼻息肉组织中的表达及与复发的关系

目的观察水通道蛋白-5（aquaporin-5，AQP5）在鼻息肉组织及正常下鼻甲黏膜组织中不同部位的表达及分布；观察AQP5在鼻息肉术后未复发及复发患者鼻息肉组织中的表达及分布；研究AQP5在鼻息肉发病机制中的作用；初步探讨AQP5在鼻息肉中的表达程度与鼻息肉复发的关系。方法取63例鼻息肉组织和13例下鼻甲组织，应用HE染色和免疫组织化学技术检NIAQP5在下鼻甲黏膜组织和鼻息肉组织中的阳性细胞的表达及分布；检NIAQP5在未复发和复发患者鼻息肉组织中的阳性细胞的表达。结果鼻息肉上皮细胞层AQP5阳性细胞表达与下鼻甲比较，差异无显著性意义（P〉0．05）；鼻息肉固有层腺体AQP5阳性细胞表达比下鼻甲显著增高，差异有显著性意义（P〈0．05）；鼻息肉血管及血窦内皮细胞AQP5阳性细胞表达比下鼻甲增高，差异有显著性意义（P〈0．05）；AQP5在鼻息肉患者术后未复发组中的阳性细胞表达显著降低，与复发组比较，差异有显著性意义（P〈0．05）。结论AQP5可能参与鼻息肉组织黏膜水肿的形成。AQP5的高表达可能与术后鼻息肉复发有一定关系。     

Upregulation of MUC8 and Downregulation of MUC5AC by Inflammatory Mediators in Human Nasal Polyps and Cultured Nasal Epithelium

Polyps are believed to be the source of mucus hypersecretion in chronic inflammation of the sinus. However, it is not clear which mucins are responsible for the hypersecretion of mucus by nasal polyps. We describe the over-expression of MUC8 mRNA in nasal polyps and the upregulation of MUC8 mRNA expression and downregulation of MUC5AC mRNA expression by inflammatory mediators. We found that the level of MUC8 mRNA, but not the level of MUC5AC mRNA, increased in nasal polyps. We also found that there was an increase in intracellular mucin in nasal polyps, compared to the normal nasal inferior turbinate. A mixture of inflammatory mediators increased MUC8 mRNA expression and decreased MUC5AC mRNA expression in cultured normal human nasal epithelial cells. Among inflammatory mediators, IL-4 is responsible for the decrease in MUC5AC mRNA and MUC5AC mucin secretion. These results indicate that MUC8 may be one of the major mucins secreted from the polyp epithelium and that it may play an important role in the pathogenesis of mucus hypersecretion in chronic sinusitis with polyps.     

Upregulation of MUC8 and downregulation of MUC5AC by inflammatory mediators in human nasal polyps and cultured nasal epithelium

Polyps are believed to be the source of mucus hypersecretion in chronic inflammation of the sinus. However, it is not clear which mucins are responsible for the hypersecretion of mucus by nasal polyps. We describe the over-expression of MUC8 mRNA in nasal polyps and the upregulation of MUC8 mRNA expression and downregulation of MUC5AC mRNA expression by inflammatory mediators. We found that the level of MUC8 mRNA, but not the level of MUC5AC mRNA, increased in nasal polyps. We also found that there was an increase in intracellular mucin in nasal polyps, compared to the normal nasal inferior turbinate. A mixture of inflammatory mediators increased MUC8 mRNA expression and decreased MUC5AC mRNA expression in cultured normal human nasal epithelial cells. Among inflammatory mediators, IL-4 is responsible for the decrease in MUC5AC mRNA and MUC5AC mucin secretion. These results indicate that MUC8 may be one of the major mucins secreted from the polyp epithelium and that it may play an important role in the pathogenesis of mucus hypersecretion in chronic sinusitis with polyps.     

Expression of MUC5AC mRNA in the goblet cells of human nasal mucosa

OBJECTIVES/HYPOTHESIS: Mucus hypersecretion is a common feature in chronic sinusitis with polyps. Because mucus hypersecretion is commonly accompanied by goblet cell hyperplasia, it is important to identify which mucin gene mRNAs are expressed in the goblet cells of the surface epithelium in the human airway. This study aims to investigate the pattern of expression of MUC5AC messenger RNA (mRNA) in the goblet cells of human nasal mucosa. METHODS: Six nasal polyps, five inferior turbinate mucosa specimens, and three normal-appearing mucosa specimens of the posterior ethmoid sinus were obtained. Each of the specimens was cut into 10-microm-thick serial frozen sections, and in situ hybridization of MUC5AC mRNA was performed with an oligonucleotide probe. Alcian blue (pH 2.5)-periodic acid-Schiff (AB-PAS) staining was performed on the serial sections. RESULTS: In human nasal polyps, MUC5AC mRNA was expressed in the cytoplasm of most of the goblet cells. However, in the inferior turbinate, MUC5AC mRNA was expressed in only some of the goblet cells. On the contrary, in the normal-appearing mucosa of the posterior ethmoid sinus, MUC5AC mRNA was barely expressed in the goblet cells. Furthermore, MUC5AC mRNA was mainly expressed in some of the PAS-positive goblet cells. CONCLUSIONS: Only a portion of the goblet cells in the human nasal mucosa expressed MUC5AC mRNA. This result suggests that surface goblet cells might have other mucin genes, in addition to MUC2 and MUC5AC.     

Effect of proinflammatory cytokines on human leucocyte antigen expression of epithelial cells of nasal polyps]

OBJECTIVE: To explore the effect of proinflammatory cytokines on the expression of human leucocyte antigen(HLA-DR) in epithelial cell of nasal polyps. METHODS: The samples were from 23 patients with nasal polyps and 11 cases of normal inferior turbinates. The samples were fixed, paraffin-embeded and sectioned for observing distribution of HLA-DR positive cells. Nasal epithelial cells were obtained after enzymatic digestion and cell culture was performed for observing influences of interleukin (IL)-1 beta and tumor necrosis factor (TNF-alpha) to expression of HLA-DR of epithelial cells and the effect of dexamethasone(10(-5) mol/L). RESULTS: The HLA-DR expression in epithelium was significantly stronger in nasal polyps than that in inferior turbinates. The expression of HLA-DR in cultured cells under stimulation of proinflammatory cytokines was increased compared with controls, but the expression was more intense in nasal polyps than that in inferior turbinates. Increased HLA-DR expression under stimulation of cytokines was reduced significantly by dexamethasone. CONCLUSION: The epithelium is in a key position to participate in inflammatory and immunologic events in the airways. Epithelial cells potentially contribute to airway inflammation by antigen presentation and the production of proinflammatory cytokines.     

白细胞介素13在嗜酸粒细胞性慢性鼻-鼻窦炎合并鼻息肉组织中的表达及其与黏蛋白高分泌的相关性研究

目的 明确白细胞介素13(IL-13)在嗜酸粒细胞性慢性鼻-鼻窦炎(eosinophilic chronic rhinosinusitis with nasal polyps,EOS-CRSwNP)中的表达,探讨在EOS-CRSwNP中IL-13和黏蛋白5AC(mucin 5AC,MUC5AC)的相关性.方法 利用免疫组化和ELISA方法观察和测量MUC5AC在对照组鼻黏膜组织和EOS-CRSwNP组织的表达,ELISA法检测IL-13在对照组鼻黏膜组织和EOS-CRSwNP组织的表达;双变量相关性分析研究EOS-CRSwNP中IL-13和MUC5AC的相关性.IL-13与原代培养鼻黏膜上皮细胞共孵育,ELISA检测细胞上清中MUC5AC的表达.结果 免疫组化染色见MUC5AC主要表达在鼻黏膜上皮,通过ELISA检测,EOS-CRSwNP中MUC5AC和IL-13均较对照组显著升高.双变量相关性分析表明在EOS-CRSwNP中MUC5AC与IL-13存在高度相关,进一步通过IL-13与气液界面原代培养人鼻黏膜上皮细胞共孵育,MUC5AC分泌显著增加.结论 MUC5AC和IL-13在EOS-CRSwNP中表达升高,MUC5AC的高分泌与IL-13高表达密切相关.     

血管通透性因子在鼻息肉中的表达及意义

目的 探讨血管通透性因子（ｖａｓｃｕｌａｒ ｐｅｒｍｅａｂｉｌｉｔｙ ｆａｃｔｏｒ，ＶＰＦ）在鼻息肉组织中的表达及意义。方法 将９例鼻息肉标本及８例下鼻甲粘膜标本行ＶＰＦ及其受体ｆｌｋ－１的免疫组化染色，光镜观查。结果 ＶＰＦ在鼻息肉组织的血管内皮细胞和腺体细胞的表达明显高于下鼻甲组织（Ｐ〈０．０１，Ｐ〈０．０５），ｆｌｋ－１在血管内皮细胞的表达明显高于下鼻甲组织（Ｐ〈０．０１）。结论 ＶＰＦ对鼻