慢性鼻窦炎鼻窦黏膜中表皮生长因子及其受体的表达

目的 观察表皮生长因子受体(epidermal growth factor receptor,EGFR)及其配体表皮生长因子(epidermal growth factor,EGF)在慢性鼻窦炎患者鼻窦黏膜中的表达及分布,探讨EGFR信号通路与慢性鼻窦炎的关系.方法 取慢性鼻窦炎伴鼻息肉患者上颔窦窦口黏膜20例(Ⅰ型和Ⅱ型各10例),另以10例正常鼻窦黏膜作为对照,应用HE染色和免疫荧光技术观察EGF和EGFR在各组鼻窦黏膜中的表达,比较阳性细胞面积比在各组间的差异.结果 EGF和EGFR在Ⅰ型和Ⅱ型慢性鼻窦炎鼻窦黏膜中均有表达,其中EGF主要表达于上皮细胞,炎性细胞和部分黏膜下腺体亦有表达;而EGFR主要表达于杯状细胞,上皮细胞和基底细胞亦有表达,两组间阳性细胞面积比差异均无统计学意义(P＞0.05).正常鼻窦黏膜中上述部位仅有弱表达或无表达,阳性细胞面积比与两病变组差异均有统计学意义(P＜0.01).结论 EGFR及其配体EGF在慢性鼻窦炎伴鼻息肉患者鼻窦黏膜中均有明显表达,EGFR信号通路可能在慢性鼻窦炎的病理机制中发挥重要作用.     

慢性鼻窦炎患者手术前后血清表皮生长因子含量的变化

目的:了解慢性鼻窦炎患者鼻内镜手术后血液中表皮生长因子(EGF)水平的变化,探讨EGF在术腔上皮化过程中可能的作用。方法:采用放射免疫方法检测慢性鼻窦炎患者手术前后血清EGF含量,研究其变化规律。结果:鼻窦炎患者血清EGF含量较正常对照组升高,但两者之间差异无统计学意义(P>0.05);不同类型鼻窦炎之间血清EGF含量也无明显差异;术后早期患者血液中的EGF较低,大约在术后4周左右降到最低水平,以后逐渐升高,8周后接近正常水平。结论:鼻窦炎患者手术前后血液中EGF的变化模式与术后黏膜的转归以及创面修复过程一致,表明EGF在术后黏膜创面修复过程中具有重要作用。     

表皮生长因子与其受体在鼻息肉上皮中的表达

目的 探讨表皮生长因子(EGF)及其受体(EGFR)在鼻息肉上皮中的表达及其意义。方法 收集鼻息肉标本25例, 正常下鼻甲黏膜组织10例, 采用免疫组化及实时荧光定量PCR技术, 观察EGF与EGFR在鼻息肉和正常下鼻甲黏膜组织中的表达情况。结果 与正常下鼻甲黏膜组织相比, EGF及EGFR的mRNA水平在鼻息肉组织中的表达下降。在免疫组化染色中, EGF及EGFR主要表达在上皮的基底层细胞, 而且在鼻息肉中的表达下降。结论 EGF及EGFR在正常鼻黏膜组织上皮的发生与修复中有着重要的作用。EGF及EGFR在鼻息肉中蛋白水平与mRNA水平表达的下降表明在鼻息肉中上皮修复功能的下调或缺失可能导致或促进鼻息肉的发生。     

重组牛碱性成纤维细胞生长因子在鼻窦黏膜术后上皮修复中的作用

目的观察重组牛碱性成纤维细胞生长因子(贝复舒液)在鼻窦黏膜术后上皮修复中的作用.方法166例行鼻内镜鼻窦手术者,术后随机分成贝复舒液组和对照组各83例.贝复舒液组应用贝复舒液和四环素可的松眼膏纱条进行术腔填塞;对照组应用四环素可的松眼膏纱条进行术腔填塞.结果贝复舒液组术腔黏膜水肿较轻,上皮化时间为(36.5±7.8)d;对照组中57例黏膜水肿明显,18例粘连予分离后好转,8例术腔黏膜水肿较轻,上皮化时间为(78.4±11.1)d.两组比较差异有统计学意义(P<0.05).治疗期间未发现局部刺激和过敏等不良反应.结论重组牛碱性成纤维细胞生长因子能安全应用于鼻内镜鼻窦手术后术腔填塞,可促进鼻窦黏膜修复,减轻窦腔黏膜水肿反应,缩短窦腔上皮化时间.     

辛夷注射液窦腔灌注治疗家兔慢性上颌窦炎

目的建立家兔慢性上颌窦炎模型,观察自制辛夷注射液对慢性上颌窦炎的治疗效果.方法家兔28只,分为4组,其中实验组24只,再分为3组.在全麻下打开上颌窦前壁裂隙植入明胶海绵并注入金黄色葡萄球菌5周后制成慢性上颌窦炎模型.①空白组窦腔内灌注生理盐水2ml;②阳性对照组窦腔灌注庆大霉素2ml(8万U);③治疗组窦腔灌注辛夷注射液2ml.并于第3、5、7天分别以同样方法重复灌注.第10天处死动物做细菌培养和病理学检查.结果治疗组共有3个窦腔培养结果为阳性,对照组13个窦腔培养结果为阳性,空白组共14个窦腔分泌物有细菌生长.1、2、3组动物所有鼻窦黏膜均有炎症表现,但轻重程度不同.治疗组黏膜基本正常,对照组和空白组黏膜上皮排列不整齐,部分变性、坏死、脱落,有小溃疡形成,黏膜充血水肿明显并有炎细胞浸润.结论辛夷注射液窦腔内灌注对慢性上颌窦炎有很好的治疗作用.     

重组人表皮生长因子在乳突根治术腔的应用

目的 探讨重组人表皮生长因子(rhEGF)在乳突根治术腔创面愈合中的作用及安全性.方法 选择52例(52耳)行乳突根治术的患者,均于术后二周拔除术腔纱条,随机分为对照组(27耳)和实验组(25耳),分别采用氧氟沙星滴耳液和rhEGF滴眼液进行术腔给药.观察术腔的分泌物多少、肉芽生长及上皮愈合情况,记录创面愈合时间、听力检查情况,并进行统计学处理,同时观察用约过程中患者局部及全身反应.结果 实验组和对照组乳突根治术腔创面的愈合时间分别平均为26.8天和38.4天,差异有统计学意义(P<0.05),实验组术腔上皮平展,疤痕少.术后听力检查两者差异无统计学意义(P>0.05).治疗及随访过程中两组均未见明显的毒副作用及不良反应.结论 重组人表皮生长因子能加快乳突根治术腔创面的愈合速度,缩短愈合时间,减少疤痕的形成,无明显毒副作用.     

功能性内镜鼻窦手术后不同鼻窦黏膜的转归规律

目的 探讨慢性鼻-鼻窦炎患者功能性内镜鼻窦手术后不同鼻窦黏膜转归的时间规律.方法 前瞻性收集77例慢性鼻-鼻窦炎患者的临床资料,在实施功能性内镜鼻窦手术后的第2周、第1、2、3、6、9、12个月采用Lund-Kennedy内镜评分方法分别对每侧鼻腔每个鼻窦进行评估,比较不同时期不同鼻窦黏膜形态的评分数值和完成上皮化比例.结果 共计154个上颌窦、154个筛窦、138个额窦和129个蝶窦纳入内镜观察与评分分析.在术后第2周,蝶窦、筛窦、上颌窦和额窦黏膜形态评分分别为(3.5±1.5)、(3.6±1.4)、(3.7±1.5)、(3.8±1.5)分,差异无统计学意义(x2=1.674,P =0.643);在术后第2、3、6、9个月,4种鼻窦黏膜的转归过程呈现明显分离趋势,依次出现黏膜评分下降拐点和上皮化比例升高峰值;在术后第12个月,蝶窦、筛窦、上颌窦、额窦评分分别为(0.4±0.1)、(0.9±0.1)、(1.4±0.2)、(2.1±0.2)分,差异有统计学意义(x2=52.691,P=0.000);且蝶窦黏膜形态评分(Z=-3.417,P =0.001)和完成上皮化的比例(x2=4.313,P=0.038)明显优于筛窦,筛窦黏膜形态评分(Z=-2.218,P=0.027)和完成上皮化比例(x2=4.292,P=0.038)明显优于上颌窦,上颌窦黏膜形态评分(Z=-2.244,P =0.025)和完成上皮化比例(x2=4.100,P =0.043)明显优于额窦.结论 功能性内镜鼻窦手术后不同鼻窦的黏膜转归存在明显时间差异,上皮化进程的先后顺序依次是蝶窦、筛窦、上颌窦和额窦.     

诱生型一氧化氮合酶在慢性上颌窦炎黏膜的表达

目的 观察诱生型一氧化氮合酶(inducible nitric oxide synthase，iNOS)在慢性鼻窦炎病人鼻窦粘膜中的表达。方法 将实验分为两组：对照组为正常成人，无鼻窦病变。实验组为确诊为慢性上颌窦炎的病人。在局麻鼻内镜下行鼻窦黏膜活检，石蜡包埋、切片，用免疫组织化学的方法观察iNOS在两组上颌窦黏膜中的表达。结果 iNOS在正常上颌窦炎黏膜呈阴性表达，在慢性上颌窦炎黏膜呈阳性表达，阳性区域主要在黏膜上皮细胞。结论 iNOS在慢性上颌窦炎黏膜呈阳性表达，提示一氧化氮在慢性上颌窦炎的发病机制中起重要作用。     

鼻内镜下鼻窦手术中保留黏膜的体会

鼻内镜下鼻窦手术中如能尽量保留窦腔黏膜,则可更好地恢复窦腔黏膜纤毛的清除功能,减少术后囊泡形成、窦口闭锁、创面粘连和瘢痕纤维化的机会,缩短创面愈合的时间,提高手术治愈率。我科自2002年10月～2006年4月共开展鼻内镜下鼻窦手术治疗慢性鼻窦炎鼻息肉患者306例,术中注意尽量保留窦腔黏膜,疗效较满意,现报告如下。     

慢性鼻窦炎手术前后血清和鼻腔分泌物中表皮生长因子水平变化

目的了解慢性鼻窦炎手术前后血清和鼻腔分泌物中表皮生长因子(epidermalgrowth factor,EGF)水平的变化,探讨EGF在鼻内镜术后术腔上皮过程中可能的作用。方法采用放射免疫方法检测慢性鼻窦炎手术患者术前及术后1、2、3、4、6、8周血清和鼻腔分泌物中EGF含量,并分析其变化规律。结果与正常对照比较,慢性鼻窦炎患者血清及鼻腔分泌物中EGF含量均升高,后者更为明显(P<0.0 5);术后第1周鼻腔分泌物中的EGF水平明显降低(P<0.05),第4周后开始升高;血清中EGF水平手术后呈缓慢下降,第6周后者开始上升。结论慢性鼻窦炎手术后血清和鼻腔分泌物中EGF水平存在一定归律的变化,这种变化模式与术后黏膜的转归以及创面修复有关,表明EGF术后鼻腔黏膜修复与上皮化过程中具有重要作用。     

葡萄球菌肠毒素B对兔上颌窦黏膜上皮电生理和通透性的影响

目的 研究葡萄球菌肠素素B（staphylococcal enterotoxin,B,SEB) 对兔上颌窦黏膜屏障功能的影响。方法 30只兔上颌窦黏膜在手术显微镜下活体取出后装于亚森室，测定上皮的短路电流、电导和通透性以及黏膜中肿瘤坏死因子－α（tumor necrosis factor α，TNF-α）。结果 葡萄球菌肠毒素B刺激引起上颌窦黏膜上皮的短路电流、电导和对辣根过氧化物酶（horseradish peroxidase,HRP)的通透性增高。用TNF－α在体外刺激窦黏膜可引起上述同样的变化。SEB刺激窦黏膜可引起其中TNF－α含量升高。经抗TNF－α抗体预处理可以阻断SEB引起的窦黏膜上皮的上述病理改变。结论 SEB可影响上颌窦上皮层的屏幕功能，可能是通过引起其中免疫细胞的功能变化，在上颌窦炎症的发生、发展中有一定的病理学意义。     

Functional recovery of rabbit maxillary sinus mucosa in two different experimental injury models

OBJECTIVE/HYPOTHESIS: Ciliary wave disorder (CWD) is essential for effective mucociliary transport. The purpose of this study was to investigate morphologic and functional restoration in recovered sinus mucosa after 12 weeks of experimentally induced rhinosinusitis and regenerated sinus mucosa after mechanical injury. STUDY DESIGN: Prospective study with animal models. METHODS: Ten New Zealand white rabbits weighing between 2.5 and 3 kg were used for this experiment. In the recovered mucosa group (n = 5), the natural ostium of the maxillary sinus was closed with a synthetic sponge and removed 2 weeks later. In the regenerated sinus mucosa group (n = 5), maxillary sinus mucosa was stripped off through the anterior wall. Left sinus mucosae were used as controls. Twelve weeks postoperatively, ciliary beat frequency (CBF) and CWD were measured using an image analysis system. Morphologic changes in cilia were also observed using a scanning electron microscope (SEM). RESULTS: The average CBFs in control, recovered, and regenerated mucosa were 13.21 +/- 3.66 Hz, 13.20 +/- 3.53 Hz, and 14.16 +/- 3.87 Hz, respectively. The average CWDs in these groups were 8.46 +/- 4.4, 21.04 +/- 14.73, and 24.43 +/- 19.2, respectively. SEM showed that loss of cilia and irregularities of ciliary arrangements were prominent in regenerated sinus mucosa. CONCLUSION: Although 12 weeks is enough for morphologic regeneration of the ciliated epithelium after experimental sinusitis in rabbit maxillary sinuses, it does not appear long enough for full functional recovery. Restoration of CBFs does not equate to concurrent CWD restoration.     

The morphological basis for the effect of substance P on mucociliary activity in rabbit maxillary sinus

The mucociliary (m.c.) activity in rabbit maxillary sinus is accelerated by the neuropeptide substance P (SP). The morphological basis for this mechanism was investigated by immunocytochemistry using monoclonal antibodies directed against SP. SP-like immunoreactivity was found in nerve fibres in the subepithelial layer of the sinus mucosa, in the maxillary nerve, and in nerve endings close to nerve cell bodies in the sphenopalatine ganglion. Thus, there is morphological evidence in the rabbit that SP plays a role in the regulation of m.c. activity. The results also support the view that the rabbit maxillary sinus is a suitable experimental model for studying SP effects in the airway mucosa.     

柯-陆手术进路上颌窦成形术的实验与临床研究

目的：探讨提高上颌窦疾病疗效的方法。方法：在动物实验的基础上,应用鼻内窥镜和显微外科技术,对６８例良性上颌窦病变,循柯－陆手术进路,行前壁环钻术和中鼻道窦造口术及骨壁修复成形术。结果：术后第５周,犬窦腔粘膜再生和修复较完全,前臂骨瓣成形骨痂愈合,临床随访１８￣４２个月（平均２８个月）中鼻道窦口通畅９６％,结论：表明上颌窦成形术在彻底清除病灶的基础上,恢复窦腔解剖结构,保持生理性引流通道,有利于术后     

The effects of natural ostium and nasoantral window on mucosal regeneration after maxillary sinus surgery in rabbits

The aims of the study were to investigate the effects of natural ostium and the nasoantral window on the mucosal regeneration after maxillary sinus surgery and to detect the changes in the mucociliary clearance during regeneration process. Twenty-eight rabbits were studied. In the study group consisting of 21 rabbits, the mucosa of each right maxillary sinus was totally removed, natural ostium was occluded with bone-wax and a nasoantral window was created, while the left sinus mucosa was removed and the natural ostium was left open without creating a nasoantral window. Maxillary sinus mucosa taken during surgery was investigated by light and electron microscopy. The study group was divided into three subgroups. The first group was followed for 2, the second for 4, and the last group for 8 weeks. At the end of these periods, the mucociliary function was evaluated scintigraphically using 99mTc-Human serum albumin. Following this investigation mucosal biopsies were taken from the right and left sinuses and the rabbits were sacrificed. In the control group consisting of 7 rabbits a small hole was opened in the anterior wall of the maxillary sinus of each rabbit and the scintigraphic evaluation was performed for this group at the end of each follow up period as well. In the histopathologic investigation, no difference was found between the natural and the nasoantral window using light microscopy, but there was a difference between them in the electron microscopic findings (p < 0.05, Chi-square test). The scintigraphic, light and electron microscopic findings and gross appearances of the sinuses are discussed.     

Effects of beta-toxin of Staphylococcus aureus on ciliary activity of nasal epithelial cells

OBJECTIVES: To investigate the in vitro effects of staphylococcal beta-toxin on ciliary activity and the in vivo effects on sinusitis induction. STUDY DESIGN: The in vitro effects of staphylococcal beta-toxin on ciliary activity were investigated at different concentrations and exposure times. Experimental sinusitis was induced in rabbits with application of beta-toxin and confirmed 7 days later. METHODS: Ciliated epithelial cells were taken from the maxillary sinus mucosa of 10 rabbits. Five culture dishes from each rabbit were used for the experimental group, and one culture dish from each rabbit was used for the control group. In the experimental group, ciliary beat frequency (CBF) was measured at concentrations of 0.1, 1, 2, 5 and 10 U/mL of beta-toxin using a video-computerized analysis technique, while in the control group, culture medium containing no toxin was used. CBF was measured 1, 2, 4, 6, 8, 12, 24, and 48 hours after administration of beta-toxin. To induce experimental sinusitis, 2 U/mL of beta-toxin was percutaneously applied to the maxillary sinus of 10 rabbits without occlusion of the natural ostium, while normal saline was percutaneously applied to the right-side maxillary sinus of 4 rabbits in the control group. At 7 days, mucosal membranes were taken from the inferomedial wall of the maxillary sinus for light microscopic study. RESULTS: CBF dropped significantly after an 8-hour incubation at 2, 5, and 10 U/mL of beta-toxin. No ciliary activity was observed after a 24-hour incubation at 2 and 5 U/mL and a 12-hour incubation at 10 U/mL of beta-toxin. Mucoid, purulent discharge was observed in the maxillary sinuses of the beta-toxin-applied group. Prominent epithelial disruption and infiltration of inflammatory cells into the epithelium and lamina propria were observed in the beta-toxin-applied group. CONCLUSIONS: Staphylococcal beta-toxin may reduce ciliary activity and induce sinusitis without occlusion of the natural ostium of the maxillary sinus in rabbits This study provides another animal model of sinusitis for understanding the pathogenesis of sinusitis induced by bacterial exotoxins.     

Experimental acute sinusitis in rabbit. A study of mucosal blood flow

An experimental model of sinusitis in the rabbit was developed, using type 3 pneumococci. The superior parts of the rabbit maxillary sinuses were surgically exposed and the maxillary ostium was unilaterally blocked. The following day a challenge dose of 10(7)-10(9) colony-forming units of Streptococcus pneumoniae, capsular type 3, was injected into the sinus. When the pneumococci used had been subjected to an animal passage, bacteria were recultured after 4 days. Histological examination showed thickening of the mucosa, with dilated venules and infiltration of granulocytes. No bacteria were seen in the mucosa on staining with acridine orange. With use of microspheres 15 micron in diameter labelled with Sn113, the mucosal blood flow was found to be higher than on the control side.     

鼻内镜术后上颌窦异常引流与黏膜炎症状态

目的观察上颌窦自然引流状态及引流的关键部位，探讨鼻内镜术后上颌窦的引流与窦腔炎症的关系，为鼻内镜手术上颌窦自然窦口的处理提供参考。方法用美蓝作为示踪剂，观察15例上颌窦无明显炎症或炎症较轻受检者上颌窦自然引流状态及引流的关键部位。另选择89例慢性鼻窦炎不伴鼻息肉患者鼻内镜术后6个月，且上颌窦黏膜恢复良好的患者，观察其上颌窦引流状态及方式，并继续随访至12个月，内镜下评估黏膜的炎症情况，分析鼻内镜术后上颌窦引流方式与黏膜炎症状态的关系。结果上颌窦自然窦口引流的关键部位在自然窦口的后下，近钩突尾端的附着处。引流物出上颌窦向后下走行，最终流向鼻咽部。传统鼻内镜手术后，引流方式相对正常者15例，占16．9％；74例（83．1％）患者上颌窦的引流状态及引流方式发生了明显改变。其中包括反向引流6例、多相引流31例、引流不能20例、“蓄水池”样改变9例以及黏膜失用8例。术后12个月33．7％的患者再次发生炎症反应，以黏膜失用炎症的发生率（100％）最高，其次是引流不能及反向引流（各占50％）。结论上颌窦自然窦口的后下近钩突尾端附着处是上颌窦引流的关键部位；鼻内镜术后，上颌窦自然引流关键部位的损伤甚至瘢痕形成，可以导致上颌窦的异常引流，过度开放上颌窦窦口，有可能加重上颌窦黏膜的损伤；上颌窦的异常引流状态及方式与黏膜炎症的发生率密切相关。     

Mucosal healing and mucociliary transport change after endoscopic sinus surgery in children with chronic maxillary sinusitis

OBJECTIVES: The aim of the study was to evaluate the effects of endoscopic sinus surgery for chronic maxillary sinusitis in children by investigating ultrastructure element changes in the sinus mucosa and nasal mucociliary clearance before and after operation. METHODS: Twenty-five children with chronic maxillary sinusitis scheduled to undergo functional endoscopic sinus surgery and another five controls were enrolled. A saccharin transit test was performed before and after the operation for each subject. Forty specimens of diseased maxillary sinus mucosa were classified into edematous and polypoid types, with 20 specimens in each type. The mucosal specimens were taken from the superolateral wall of each maxillary sinus during surgery and at post-operative follow-up when the mucosal recovery had begun and the symptoms had subsided. The specimens were examined with a scanning electron microscope. RESULTS: A significant increase in number of the submucosal gland openings (GO) was noted for the sinusitis group, of both edematous and polypoid types. In post-operative cases, the number of gland openings decreased, however, it remained higher than for the control group. The number of goblet cells (GC) decreased in the sinusitis cases, and significant difference was not demonstrated compared to postoperative and control groups. After endoscopic sinus surgery, the cilia in both types of antral mucosa were significantly regenerated compared to preoperative variants. Significant differences in postoperative saccharin transit time were demonstrated for both types of antral mucosa compared to the preoperative values. CONCLUSION: After endoscopic sinus surgery for chronic pediatric sinusitis, the antral mucosa recovered and mucociliary clearance improved for both types of antral mucosa, with improved ventilation and drainage demonstrated for our patients. Based on our specimens, the edematous mucosa appear to regenerate sooner than the polypoid variant, with close post-operative follow-up for more than 2 and 4 months for the edematous and polypoid types of antral mucosa, respectively, necessary to prevent sinusitis relapse.     

Paranasal sinus mucosal regeneration: the effect of topical retinoic acid

BACKGROUND: Paranasal sinus mucosa may suffer morphological and functional alterations as a result of surgical trauma. Mucosal stripping typically yields regenerated mucosa characterized by fibrosis, inflammatory infiltrate, and dysmorphic or absent cilia. The aim of this study was to determine the effect of topical retinoic acid (vitamin A) on regeneration of paranasal sinus mucosa. METHODS: Both maxillary sinuses of 12 New Zealand white rabbits were surgically opened and stripped of mucosa. Six rabbits received 0.01% topical retinoic acid gel treatment to the stripped left maxillary sinus (low concentration group). The remaining six rabbits received 0.025% topical retinoic acid gel to the stripped left maxillary sinus (high concentration group). The stripped right maxillary sinus of all 12 rabbits served as the operated, untreated control to reflect the normal healing process. Six other animals served as unoperated controls. The sinus mucosa was examined by light microscopy after 14 days. RESULTS: Untreated regenerated mucosa showed expected changes of submucosal gland loss, basal lamina and lamina propria fibrosis, cellular atypia, and loss of cilia. Topical retinoic acid treatment appeared to result in better mucosal regeneration marked by less cellular atypia and fibrosis. Although the regenerated mucosa was still grossly abnormal, the degree of ciliary loss and cellular derangement was reduced. The lower-concentration retinoic acid group had more favorable morphology than the higher-concentration retinoic acid group, and both were improved when compared with no treatment. CONCLUSIONS: In a rabbit model, topical vitamin A in the form of retinoic acid gel appears to enhance regeneration of ciliated paranasal sinus mucosa. This preliminary study suggests that topical retinoids may have applicability in promoting sinus wound healing.