鼻窦炎术后黏膜组织形态学和生理功能变化及其临床意义
摘要
目的
慢性鼻窦炎、鼻息肉约占耳鼻咽喉临床处置和手术的四分之一，全国累计发病人口近千万。长期以来对于慢性鼻窦炎的定义一直缺乏统一的认识，这阻碍了人们对其病因、病理生理学的深入研究。近年来，随着鼻科学及相关基础学科的发展，人们对慢性鼻窦炎的定义展开了广泛的讨论，同时认识到慢性鼻窦炎是多种因素相互影响、相互作用的结果，临床上针对这些环节进行综合治疗有助于提高疗效、减少复发。1993年国际鼻窦疾病会议将慢性鼻窦炎定义为症状和体征持续8周以上或反复发生的急性鼻窦炎每年发作4次以上，每次至少持续10d。但疾病的最后诊断仍依赖于病理诊断，因此找到一种以病理学改变为基础、易于在临床上展开的定义仍将是耳鼻咽喉科工作者的一大任务。研究发现其致病因素包括：（1）细菌感染；（2）鼻及鼻窦解剖变异；（3）原发或继发黏膜纤毛功能障碍；（4）变态反应性因素等。光镜下观察慢性鼻窦炎鼻息肉鼻黏膜正常结构破坏，鼻窦黏膜结构和功能的破坏是慢性鼻窦炎鼻息肉发病的关键。慢性鼻窦炎又可以进一步影响鼻窦黏膜的功能，形成恶性循环。Forsgren等与Tos等发现慢性鼻窦炎黏膜鳞状上皮化生，杯状细胞增多，基底膜增厚、水肿炎性细胞浸润，黏膜下腺体增生，黏膜纤维化，息肉形成及病理性腺体。黏膜层内大量炎性细胞浸润，有文献报道主要为淋巴细胞及单核细胞，也有文献报道主要为中性粒细胞。针对其病
因可采取多种治疗方法如抗生素治疗、上颌窦穿刺及鼻腔局部用药等保守治疗。近20年来，随着鼻内窥镜的引入，功能性鼻内镜手术（FESS）已成为治疗慢性鼻窦炎鼻息肉的重要手段。对慢性鼻窦炎的治疗应首选药物治疗，只有在规范的药物治疗无效或发生并发症的情况下才考虑手术治疗。FESS最基本的出发点是在彻底清除不可逆病变的基础上，以重建鼻腔、鼻窦通气和引流作为改善和恢复鼻腔、鼻窦黏膜形态和生理功能的基本条件为目的来治愈鼻窦炎，并依靠鼻腔、鼻窦自身生理功能的恢复抵御外界致病因子的侵袭来防止病变的复发，即通过小范围的或局限性的手术解决相对广泛的鼻窦病变。而手术仅仅是整体治疗环节中的一个重要步骤，手术结束紧接着的是黏膜上皮再生和恢复阶段，那末鼻窦炎术后术腔黏膜形态和生理功能恢复有何规律，标志治愈的“黏膜上皮化”的上皮组织是何种上皮尚需给予研究、论证。目前国内外大多数学者将研究重点放在对慢性鼻窦炎鼻息肉患者FESS术前/术后细胞、亚细胞及分子水平的研究上，以探讨鼻内镜手术对鼻腔鼻窦黏膜形态和功能的影响，评价FESS手术的有效性，尚缺乏对慢性鼻窦炎FESS术后黏膜的动态观察研究。
材料方法
本实验通过对慢性鼻窦炎鼻息肉患者Ⅱ型3期15例，Ⅲ型5例术后4个月和10个月两个不同阶段术腔黏膜的组织形态、免疫活性细胞数量以及清除外源病原的黏液纤毛输送功能进行观察研究，采用光镜观察、免疫组织化学染色法和糖精法，用于光
镜和免疫组化的标本均为术后4个月和10个月随访时，用镰状刀切取患者前筛区，即钩突切除后切缘后方。
结果
1、术后4个月组：20例CSNP患者，其中头痛5例，鼻塞4例，脓涕8例，嗅觉减退5例；内窥镜检查：术腔上皮化10例，水肿5例，肉芽1例，粘连2例，囊泡2例。术后10个月组：头痛1例，鼻塞1例，脓涕2例，嗅觉减退3例，症状消失13例；内窥镜检查：术腔上皮化17例，水肿1例，肉芽0例，粘连2例，囊泡0例。
2、光镜观察术后4个月筛区黏膜上皮有2例（10％，均为Ⅲ型）为鳞-柱交界上皮；术后10个月筛区黏膜基本恢复为假复层柱状纤毛上皮但纤毛细胞较正常黏膜上皮稀疏，排列欠规整。
3、糖精实验术后4个月与术后10个月及正常对照组MTR之间均存在显著差异（p<0.05），术后10个月与正常对照组间无显著差异。
4、免疫组织化学染色法结果显示：术后4个月IL-2、TNF-α阳性细胞数明显高于健康对照组（p<0.01）及术后10个月组（p<0.05）；术后10个月IL-2、TNF-α阳性细胞数与健康对照组无明显差异（p>0.05）。
结论
1、本研究发现，慢性鼻窦炎鼻息肉患者FESS术后筛区黏膜组织的恢复是一个由鳞状上皮、鳞柱交界上皮向假复层柱状纤毛上皮演变的过程。
2、慢性鼻窦炎鼻息肉术后随着筛区粘膜组织学的恢复，纤毛清除速率和免疫活性细胞数量等黏膜生理功能指标逐渐恢复至正常水平。
3、术后4个月术区粘膜仍不稳定，且处于病变恢复阶段，因此术后随访应不少于4个月或更长，以防止复发。
4、FESS术后干预措施，如术腔灌洗、局部和全身应用糖皮质类固醇，尤其是糖皮质激素的应用对于慢性鼻窦炎鼻息肉患者术后黏膜形态及生理功能的恢复至关重要。
5、FESS是目前治疗慢性鼻窦炎鼻息肉理想的手术方法。FESS具有手术创伤小，切除病变部位明确，并发症少，治愈率高的优点。
6、CSNP各型FESS术后黏膜组织形态及生理功能转归速度及规律不尽相同。
Sinusitis is a common health problem in both children and adults. It can be defined as inflammation of the paranasal sinuses, the etiology of which includes both infectious agents and also allergic mechanisms. While sinusitis can be categorized in many ways, the most common description is by duration of symptoms. Chronic sinusitis refers to symptoms lasting more than 3 months. The pathogenesis of sinusitis is multifactorial and involves a complex interaction between host defense mechanisms and the infecting organisms. The treatment of chronic sinusitis has four objectives: to control infection, to reduce tissue edema, to facilitate the drainage of sinus secretions and to maintain ostial permeability. Medical treatment includes antibiotics, decongestants, mucolytics, steroids and analgesics. Surgical treatment may be conservative, functional or radical. At present, “FESS” is the “Golden Standard”. It is focused on the middle ostiomeatal complex and the ethmoid cells .So the blockade of sinonasal drainage by anatomical abnormalities (like paradoxicity of middle turbinate, e.g. convexity facing laterally; concha bullosa, e.g. aircells in the head of middle turbinate, variation in the uncinate process and large ethmoid bulla) and zuxtaposition of mucosalabutting surfaces in chronic inflammation will predispose to different sinus conditions like inflammatory and polyp pathology
due to stenosis in middle meatus. So endoscopic endonasal surgery of diseased ethmoid is important in treatment of chronic sinusitis. Endoscopic sinus surgery has enjoyed impressive success curing chronic disease in sinuses and has virtually replaced the Caldwell-Luc procedure for correction of problems with sinuses.
With the introduction of nasal endoscopy, functional endoscopic sinus surgery(FESS) has become an important means in treating chronic sinusitis and polyps. To investigate the regulation of the morphological and functional mucosal recovering after FESS and the epithelial type indicating epithelization, light microscopic examination, saccharin test and immunohistochemical streptavidinbitin peroxidae complex (SABC) method were taken at 4m and 10m after operation in 20 cases with chronic sinusitis and 10 normal subjects as control. The mucosa specimens were taken from the anterior ethmoid, that is the posterior removing edge of uncinate process. The tests showed that (1) Squamous cells and squamous continuing peseudostratified ciliated columnar epithelium were observed in 15% patients at 4m postoperatively. And peseudostratified ciliated columnar epithelium at 10m after operation. (2) Mucociliary transport rate (MTR) in patients at 4m postoperatively was significantly longer than that in the patients at 10m and the controls, and there was no significantly difference between the controls and the patients at 10m postoperatively. (3) The
numbers of inflammatory cell, that is the immunocompetent cells in patients at 4m postoperatively was significantly more than those in the healthy control (p<0.01) and patients at 10m.There was no significantly difference between the healthy control and patients at 10m. In conclusion, the study showed a benign process of the morphological and histological transitionary of sinus mucosa in patients with chronic sinusitis and polyps after FESS at two periods:4 months and 10 months. And the physiological function, the clearance function of mucociliary system of the operative cavity in nasal middle meatus and protective role of the immumocompetent cells were also improved. These results also provided theoretical foundation for the proper local care postoperatively. It is of great importance to reduce the recurrence rate of chronic sinusitis and nasal polyps and improve the curable rate.
慢性鼻窦炎、鼻息肉约占耳鼻咽喉临床处置和手术的四分之一，全国累计发病人口近千万。长期以来对于慢性鼻窦炎的定义一直缺乏统一的认识，这阻碍了人们对其病因、病理生理学的深入研究。近年来，随着鼻科学及相关基础学科的发展，人们对慢性鼻窦炎的定义展开了广泛的讨论，同时认识到慢性鼻窦炎是多种因素相互影响、相互作用的结果，临床上针对这些环节进行综合治疗有助于提高疗效、减少复发。1993年国际鼻窦疾病会议将慢性鼻窦炎定义为症状和体征持续8周以上或反复发生的急性鼻窦炎每年发作4次以上，每次至少持续10d。但疾病的最后诊断仍依赖于病理诊断，因此找到一种以病理学改变为基础、易于在临床上展开的定义仍将是耳鼻咽喉科工作者的一大任务。研究发现其致病因素包括：（1）细菌感染；（2）鼻及鼻窦解剖变异；（3）原发或继发黏膜纤毛功能障碍；（4）变态反应性因素等。光镜下观察慢性鼻窦炎鼻息肉鼻黏膜正常结构破坏，鼻窦黏膜结构和功能的破坏是慢性鼻窦炎鼻息肉发病的关键。慢性鼻窦炎又可以进一步影响鼻窦黏膜的功能，形成恶性循环。Forsgren等与Tos等发现慢性鼻窦炎黏膜鳞状上皮化生，杯状细胞增多，基底膜增厚、水肿炎性细胞浸润，黏膜下腺体增生，黏膜纤维化，息肉形成及病理性腺体。黏膜层内大量炎性细胞浸润，有文献报道主要为淋巴细胞及单核细胞，也有文献报道主要为中性粒细胞。针对其病
因可采取多种治疗方法如抗生素治疗、上颌窦穿刺及鼻腔局部用药等保守治疗。近20年来，随着鼻内窥镜的引入，功能性鼻内镜手术（FESS）已成为治疗慢性鼻窦炎鼻息肉的重要手段。对慢性鼻窦炎的治疗应首选药物治疗，只有在规范的药物治疗无效或发生并发症的情况下才考虑手术治疗。FESS最基本的出发点是在彻底清除不可逆病变的基础上，以重建鼻腔、鼻窦通气和引流作为改善和恢复鼻腔、鼻窦黏膜形态和生理功能的基本条件为目的来治愈鼻窦炎，并依靠鼻腔、鼻窦自身生理功能的恢复抵御外界致病因子的侵袭来防止病变的复发，即通过小范围的或局限性的手术解决相对广泛的鼻窦病变。而手术仅仅是整体治疗环节中的一个重要步骤，手术结束紧接着的是黏膜上皮再生和恢复阶段，那末鼻窦炎术后术腔黏膜形态和生理功能恢复有何规律，标志治愈的“黏膜上皮化”的上皮组织是何种上皮尚需给予研究、论证。目前国内外大多数学者将研究重点放在对慢性鼻窦炎鼻息肉患者FESS术前/术后细胞、亚细胞及分子水平的研究上，以探讨鼻内镜手术对鼻腔鼻窦黏膜形态和功能的影响，评价FESS手术的有效性，尚缺乏对慢性鼻窦炎FESS术后黏膜的动态观察研究。
材料方法
本实验通过对慢性鼻窦炎鼻息肉患者Ⅱ型3期15例，Ⅲ型5例术后4个月和10个月两个不同阶段术腔黏膜的组织形态、免疫活性细胞数量以及清除外源病原的黏液纤毛输送功能进行观察研究，采用光镜观察、免疫组织化学染色法和糖精法，用于光
镜和免疫组化的标本均为术后4个月和10个月随访时，用镰状刀切取患者前筛区，即钩突切除后切缘后方。
结果
1、术后4个月组：20例CSNP患者，其中头痛5例，鼻塞4例，脓涕8例，嗅觉减退5例；内窥镜检查：术腔上皮化10例，水肿5例，肉芽1例，粘连2例，囊泡2例。术后10个月组：头痛1例，鼻塞1例，脓涕2例，嗅觉减退3例，症状消失13例；内窥镜检查：术腔上皮化17例，水肿1例，肉芽0例，粘连2例，囊泡0例。
2、光镜观察术后4个月筛区黏膜上皮有2例（10％，均为Ⅲ型）为鳞-柱交界上皮；术后10个月筛区黏膜基本恢复为假复层柱状纤毛上皮但纤毛细胞较正常黏膜上皮稀疏，排列欠规整。
3、糖精实验术后4个月与术后10个月及正常对照组MTR之间均存在显著差异（p<0.05），术后10个月与正常对照组间无显著差异。
4、免疫组织化学染色法结果显示：术后4个月IL-2、TNF-α阳性细胞数明显高于健康对照组（p<0.01）及术后10个月组（p<0.05）；术后10个月IL-2、TNF-α阳性细胞数与健康对照组无明显差异（p>0.05）。
结论
1、本研究发现，慢性鼻窦炎鼻息肉患者FESS术后筛区黏膜组织的恢复是一个由鳞状上皮、鳞柱交界上皮向假复层柱状纤毛上皮演变的过程。
2、慢性鼻窦炎鼻息肉术后随着筛区粘膜组织学的恢复，纤毛清除速率和免疫活性细胞数量等黏膜生理功能指标逐渐恢复至正常水平。
3、术后4个月术区粘膜仍不稳定，且处于病变恢复阶段，因此术后随访应不少于4个月或更长，以防止复发。
4、FESS术后干预措施，如术腔灌洗、局部和全身应用糖皮质类固醇，尤其是糖皮质激素的应用对于慢性鼻窦炎鼻息肉患者术后黏膜形态及生理功能的恢复至关重要。
5、FESS是目前治疗慢性鼻窦炎鼻息肉理想的手术方法。FESS具有手术创伤小，切除病变部位明确，并发症少，治愈率高的优点。
6、CSNP各型FESS术后黏膜组织形态及生理功能转归速度及规律不尽相同。
Sinusitis is a common health problem in both children and adults. It can be defined as inflammation of the paranasal sinuses, the etiology of which includes both infectious agents and also allergic mechanisms. While sinusitis can be categorized in many ways, the most common description is by duration of symptoms. Chronic sinusitis refers to symptoms lasting more than 3 months. The pathogenesis of sinusitis is multifactorial and involves a complex interaction between host defense mechanisms and the infecting organisms. The treatment of chronic sinusitis has four objectives: to control infection, to reduce tissue edema, to facilitate the drainage of sinus secretions and to maintain ostial permeability. Medical treatment includes antibiotics, decongestants, mucolytics, steroids and analgesics. Surgical treatment may be conservative, functional or radical. At present, “FESS” is the “Golden Standard”. It is focused on the middle ostiomeatal complex and the ethmoid cells .So the blockade of sinonasal drainage by anatomical abnormalities (like paradoxicity of middle turbinate, e.g. convexity facing laterally; concha bullosa, e.g. aircells in the head of middle turbinate, variation in the uncinate process and large ethmoid bulla) and zuxtaposition of mucosalabutting surfaces in chronic inflammation will predispose to different sinus conditions like inflammatory and polyp pathology
due to stenosis in middle meatus. So endoscopic endonasal surgery of diseased ethmoid is important in treatment of chronic sinusitis. Endoscopic sinus surgery has enjoyed impressive success curing chronic disease in sinuses and has virtually replaced the Caldwell-Luc procedure for correction of problems with sinuses.
With the introduction of nasal endoscopy, functional endoscopic sinus surgery(FESS) has become an important means in treating chronic sinusitis and polyps. To investigate the regulation of the morphological and functional mucosal recovering after FESS and the epithelial type indicating epithelization, light microscopic examination, saccharin test and immunohistochemical streptavidinbitin peroxidae complex (SABC) method were taken at 4m and 10m after operation in 20 cases with chronic sinusitis and 10 normal subjects as control. The mucosa specimens were taken from the anterior ethmoid, that is the posterior removing edge of uncinate process. The tests showed that (1) Squamous cells and squamous continuing peseudostratified ciliated columnar epithelium were observed in 15% patients at 4m postoperatively. And peseudostratified ciliated columnar epithelium at 10m after operation. (2) Mucociliary transport rate (MTR) in patients at 4m postoperatively was significantly longer than that in the patients at 10m and the controls, and there was no significantly difference between the controls and the patients at 10m postoperatively. (3) The
numbers of inflammatory cell, that is the immunocompetent cells in patients at 4m postoperatively was significantly more than those in the healthy control (p<0.01) and patients at 10m.There was no significantly difference between the healthy control and patients at 10m. In conclusion, the study showed a benign process of the morphological and histological transitionary of sinus mucosa in patients with chronic sinusitis and polyps after FESS at two periods:4 months and 10 months. And the physiological function, the clearance function of mucociliary system of the operative cavity in nasal middle meatus and protective role of the immumocompetent cells were also improved. These results also provided theoretical foundation for the proper local care postoperatively. It is of great importance to reduce the recurrence rate of chronic sinusitis and nasal polyps and improve the curable rate.
引文
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汪银凤, 叶非常, 王明善. 功能性内窥镜鼻窦手术对不同型期鼻窦炎鼻黏液纤毛清除率的影响. 临床耳鼻咽喉科杂志, 2000, 14: 339-341
李延忠, 房振胜, 杜志华, 等. 慢性鼻窦炎上颌窦黏膜促炎细胞因子的免疫组化表达.中华耳鼻咽喉科杂志, 2002, 37: 465-466
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贺广湘, 孙虹, 等. 慢性鼻窦鼻内窥镜手术前后鼻粘膜观察. 中华耳鼻咽喉科杂志, 2001, 36(5): 326-329
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何春燕, 刘红刚, 王先忠, 等. 慢性鼻窦炎鼻息肉筛窦黏膜病理形态学研究. 中华耳鼻咽喉科杂志, 2003, 38: 89-91
汪银凤, 叶非常, 王明善. 功能性内窥镜鼻窦手术对不同型期鼻窦炎鼻黏液纤毛清除率的影响. 临床耳鼻咽喉科杂志, 2000, 14: 339-341
李延忠, 房振胜, 杜志华, 等. 慢性鼻窦炎上颌窦黏膜促炎细胞因子的免疫组化表达.中华耳鼻咽喉科杂志, 2002, 37: 465-466
中华医学会耳鼻咽喉科学会, 中华耳鼻咽喉科杂志编辑委员会. 慢性鼻窦炎鼻息肉临床分型分期内窥镜手术疗效评定标准 (1997年, 海口). 中华耳鼻咽喉科杂志, 1998, 33: 216-218
许庚, 功能性内窥镜鼻窦外科的基本术式. 许庚, 李源, 主编. 内窥镜鼻窦外科学. 广州: 暨南大学出版社, 1994, 131-144
孙宇新, 董震, 杨占泉. 中鼻道粘液纤毛系统清除功能的研究. 临床耳鼻咽喉杂志, 2002, 16(10): 530-532
贺广湘, 孙虹, 等. 慢性鼻窦鼻内窥镜手术前后鼻粘膜观察. 中华耳鼻咽喉科杂志, 2001, 36(5): 326-329
Stierna P, Carisoo B. Histopathological observation in chronic maxillary sinusitis. Acta Otolaryngol, 1990, 110: 450-458
黄选兆, 汪吉宝, 主编, 实用耳鼻咽喉科学. 北京: 人民卫生出版社, 1998, 116
武忠弼. 超微病理学基础. 北京: 人民卫生出版社, 1990, 7-8
Mijailovich LM et al. Biophys J, 1996; 71; 1475-1484
陈慰峰. 医学免疫学. 北京: 人民卫生出版社, 2002, 46
Biedlingnaier J F, Trifillis A. Camparison of CT scan and electron microscopic findings on endoscopically harvested middle turbinates. Otolaryngol Head Neck Surg, 1998, 118: 165-173
黄选兆, 汪吉宝, 主编. 实用耳鼻咽喉科学. 北京: 人民卫生出版社, 1998, 116
李源, 许庚, 等. 慢性鼻窦炎鼻息肉鼻内窥镜手术后综合处理意见. 中华耳鼻咽喉科杂志, 2001, 26(3): 237-240
Watelat JB et al. Wound healing of the nasal and paranasal mucosa: a review. AM J Rhinal, 2002; 16: 77-84
姜舒, 董震. 鼻粘膜上皮层在炎症反应中的主动应答作用. 国外医学耳鼻咽喉科学分册, 2002, 26(2): 87-91
许庚, 李源, 谢民强, 等. 功能性内窥镜手术后术腔粘膜转归阶段的划分及处理原则. 中华耳鼻咽喉科杂, 1999, 4: 302-305
苏志文, 邱前辉, 陈少华, 等. 内窥镜鼻窦术后中鼻道粘膜的超微病理结构变化.临床耳鼻咽喉科杂志, 1999, 13: 216-218
王正国. 创伤修复与生长因子. 中国修复重建外科杂志. 1999, 13(5): 257-258