慢性鼻-鼻窦炎的组织重塑研究进展

慢性鼻-鼻窦炎的病理特点是鼻腔及鼻窦黏膜存在持续炎症浸润,依据是否存在鼻息肉,被分为伴息肉及不伴息肉型。现有的研究表明,慢性鼻-鼻窦炎的发生、发展中存在组织重塑,其中TGF-β及基质金属蛋白酶是影响重塑最重要的细胞因子。研究重塑过程中的细胞因子及其作用机制,有助于选择最佳的治疗靶点。未来研究应进一步明确慢性鼻-鼻窦炎组织重塑复杂径路。     

基质金属蛋白酶与慢性鼻及鼻窦炎和鼻息肉组织重塑

组织蕈塑是组织损伤后组织结构的重新构建,近年来研究发现基质金属蛋白酶参与了慢性鼻及鼻窦炎和鼻息肉的组织重塑,本文就基质金属蛋白酶在慢性鼻及鼻窦炎和鼻息肉组织重塑中的作用进行综述.     

基质金属蛋白酶及其抑制剂与喉癌的浸润和转移

喉癌是头颈部常见的恶性肿瘤,喉癌的浸润与转移是影响治疗效果和预后的主要因素。基质金属蛋白酶及基质金属蛋白酶抑制剂是调节许多生理和病理过程中细胞外基质及基底膜有序降解和重塑的重要分子。细胞外基质和基底膜的降解在喉癌和其他肿瘤的浸润转移过程中起重要作用,基质金属蛋白酶及其抑制剂在细胞外基质和基底膜的代谢平衡中起关键作用,因而与喉癌的浸润转移密切相关。本文对基质金属蛋白酶及其抑制剂在喉癌中的表达与喉癌浸润转移及预后的相关性作一综述,并对指导喉癌治疗进行了展望。     

布地奈德对不伴鼻息肉的慢性鼻-鼻窦炎术后鼻黏膜细胞外基质的影响

目的　观察布地奈德对不伴鼻息肉的慢性鼻-鼻窦炎（CRS without nasal polyps,CRSsNP）鼻内镜术后鼻黏膜细胞外基质（extracellular matrix,ECM）及基质金属蛋白酶9（matrix metalloproteinase-9,MMP-9）表达的影响。方法　30例行鼻内镜手术的CRSsNP患者术后随机分为两组,布地奈德组20例（术后布地奈德喷鼻3个月）,对照组10例（术后未使用糖皮质激素）,术后3个月随访时留取筛区黏膜标本,并对患者行视觉模拟量表主观症状评分及Lund-Kennedy法鼻内镜评分,所有标本行Masson三色（MT）胶原染色及苦味酸-天狼星红染色,观察鼻黏膜基底膜区及黏膜内固有层ECM胶原沉积及成分等情况,免疫组化检测MMP-9的表达。结果　①与对照组相比,布地奈德组的VAS评分及鼻内镜评分均明显降低（t =-2.489,P =0.019;t =-3.318,P =0.003）。②布地奈德组鼻黏膜在基底膜区及黏膜内固有层ECM胶原沉积较对照组均明显减少（t =15.242,P =0.000;t =7.179,P =0.000）。③两组ECM沉积的胶原均以Ⅰ型胶原纤维为主,Ⅲ型、Ⅳ型胶原较少。④布地奈德组鼻黏膜内MMP-9的表达较对照组明显减少（t =9.173,P =0.000）。结论　布地奈德能减少CRSsNP鼻内镜术后鼻黏膜ECM胶原的沉积,改善鼻内镜术后疗效,降低MMP-9的表达可能是其中机制之一。     

基质金属蛋白酶及其抑制剂与喉癌的浸润和转移

喉癌是头颈部常见的恶性肿瘤，喉癌的浸润与转移是影响治疗效果和预后的主要因素。基质金属蛋白酶及基质金属蛋白酶抑制剂是调节许多生理和病理过程中细胞外基质及基底膜有序降解和重塑的重要分子。细胞外基质和基底膜的降解在喉癌和其他肿瘤的浸润转移过程中起重要作用，基质金属蛋白酶及其抑制剂在细胞外基质和基底膜的代谢平衡中起关键作用，因而与喉癌的浸润转移密切相关。本文对基质金属蛋白酶及其抑制剂在喉癌中的表达与喉癌浸润转移及预后的相关性作一综述，并对指导喉癌治疗进行了展望。     

MMPs及TIMPs诱导血管生成在中耳胆脂瘤增殖中的作用

胆脂瘤上皮细胞存在异常的高度增殖能力,胆脂瘤基质周围新生血管形成和微循环的重建为胆脂瘤上皮的异常增殖提供较丰富的血供和营养。胆脂瘤上皮由于受到所处微环境中的炎症因子、细胞因子的刺激,导致基质金属蛋白酶家族（MMPs）高表达并诱导新生血管形成。MMPs在血管生成作用中不只是起到降解细胞外基质（ECM）作用,它们还可以通过调整内皮细胞黏附、增殖、转移和生长或者直接通过释放基质中隐藏的血管生长因子促进血管生成。此外,ECM涉及组织稳态和肿瘤浸润及炎症等病理过程,MMPs和TIMPs是维持ECM稳态的重要因素,MMPs TIMPs活力失衡可能对胆脂瘤增殖及骨质破坏吸收有重要影响。     

基质金属蛋白酶与OSAHS的相关性研究进展

基质金属蛋白酶（Matrix metalloproteinase,MMPs）是自然界进化的高度保守的一类内源性蛋白水解酶,广泛分布在自然界各种生物中,通过降解细胞外基质中的多种蛋白成分在良恶性病变的发生、发展中发挥着重要作用。阻塞性睡眠呼吸暂停低通气综合征（Obstructive sleep apnea-hypopnea syndrome,OSAHS）是一种常见的睡眠呼吸障碍性疾病。本文主要对基质金属蛋白酶（MMPs）与OSAHS的相关性做一综述。     

基质金属蛋白酶及其组织抑制因子在慢性鼻-鼻窦炎中的研究进展

慢性鼻-鼻窦炎是一组多种致病因素参与、多种信号途径调节以及多基因调控的疾病。其在组织形态学上存在与哮喘相似的气道黏膜重塑改变,表现为黏膜上皮损 伤、基底膜增厚等非特异性改变,以及黏膜组织水肿及胶原沉积、纤维化等特异性改变等。这些表现与鼻腔鼻窦黏膜细胞外基质动态失衡密切相关,而基质金属蛋白酶是目前已知降解细胞外基质最重要的酶类之一。本文就基质金属蛋白酶及其组织抑制因子在慢性鼻-鼻窦炎不同临床表型中的研究进展进行综述。     

RECK基因与头颈部鳞状细胞癌

RECK是新发现的一种基质金属蛋白酶家族(matrix metalloproteinases,MMPs)抑制剂和肿瘤抑制基因,它在肿瘤组织中的表达能抑制肿瘤的侵袭和转移.相关研究发现此作用与细胞外基质(extracellular matrix,ECM)、MMPs和金属蛋白酶组织抑制因子(tissue inhibitor of metalloproteinases,TIMPs)密切相关.现就RECK与ECM、MMPs、TIMPs之间的相互作用及其与头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)的侵袭和转移关系做一综述,以期为头颈部肿瘤的治疗和研究提供帮助.     

基质金属蛋白酶及其组织抑制剂与原发性开角型青光眼的研究

原发性开角型青光眼的发病机制与小梁和睫状肌部位细胞外基质的异常沉积密切相关,基质金属蛋白酶及其组织抑制剂通过 调节细胞外基质的降解和代谢平衡参与了原发性开角型青光眼的发病机制。     

Matrix metalloproteinases and their inhibitors in non-neoplastic otorhinolaryngological disease

Matrix metalloproteinases (MMPs) are a family of zinc and calcium-dependent endopeptidases that play a key role in extracellular matrix (ECM) degradation. MMPs are known to be important in normal remodelling processes. Overexpression and activation of MMPs or an imbalance of active MMPs and tissue inhibitors of metalloproteinases (TIMPs) has been linked with a number of specific disease states associated with the breakdown and remodelling of the extracellular matrix. MMPs and TIMPs play a role in the development and progression of conditions such as acute and chronic otitis media, nasal polyposis and Sjogren's disease of salivary glands. Their role in allergic rhinitis has not been proven although they do appear to have a role in asthma, a condition closely linked to rhinitis. The use of a broad spectrum MMP inhibitor has been shown to alter the outcome of acute otitis media and otitis media with effusion. Therapeutic strategies with anti-MMP molecules are currently being developed and may play a role in modulating the course of non-neoplastic otorhinolaryngological disease in the future.     

Expression of collagenase-1 (MMP-1), collagenase-3 (MMP-13) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in laryngeal squamous cell carcinomas

Matrix metalloproteinases (MMPs) that have a proteolytic activity against the components of extracellular matrix (ECM) play an important role in the invasive and metastatic spread of tumors. The role of MMPs and tissue inhibitors of MMPs (TIMPs) in laryngeal squamous cell carcinoma (LSCC) has not been elucidated sufficiently. The aim of the present study was to evaluate the correlation between the expression of collagenase-1 (MMP-1), collagenase-3 (MMP-13) and TIMP-1, as well as the clinicopathological features of LSCCs. The expression of collagenases and TIMP-1 was examined immunohistochemically in 50 cases of surgically obtained specimens of primary LSCCs. Analyses indicated that LSCC cells as well as stromal cells expressed MMP-1, MMP-13 and TIMP-1 immunostaining. Overexpression of TIMP-1 occurred more frequently in non-metastasizing cases (P=0.009). TIMP-1 and MMP-1 staining correlated significantly with the histologic type of LSCC. The keratinizing type of carcinomas exhibited higher TIMP-1 protein expression than the nonkeratinizing variety (P=0.01). TIMP-1 staining was associated with the grade of differentiation, since it was found predominantly in well and moderately differentiated carcinomas (P=0.04). The findings confirm that expression of analyzed MMPs and TIMP-1 is characteristic of LSCC and that these enzymes contribute to the progression of tumors. TIMP-1 upregulation might exhibit lower metastatic potential in LSCCs and is linked rather with an early stage of tumor progression. It seems also that TIMP-1 expression is dependent on the grade of differentiation.     

Expression of matrix metalloproteinases and their inhibitors in squamous cell carcinoma of the tonsil and their clinical significance

Objectives

To investigate expressions of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in squamous cell carcinoma of the tonsil and to correlate expression profiles with clinicopathological characteristics.

Methods

Paraffin blocks were obtained from 45 tonsil squamous cell carcinoma (SCC) patients, who underwent surgery as an initial treatment between 1994 and 2004, and from 20 normal controls. Expressions of MMP-2, MMP-9, MMP-13, TIMP-1, and TIMP-2 were investigated immunohistochemically.

Results

The expressions of MMPs (except MMP-2) and TIMPs were found to be significantly different in tonsil SCC and normal control tissues. Furthermore, MMP-13 expression was found to be correlated with tumor invasion (P=0.05), and the expressions of MMP-9 and TIMP-1 with nodal metastasis (P=0.048, 0.031). No relation was found between MMP or TIMP expression and recurrence. However, MMP-9 expression was found to be significantly associated with 5-year survival in tonsil SCC patients by multivariate analysis (hazard ratio, 3.853; P=0.013).

Conclusion

Significant overexpressions of multiple MMPs and TIMPs were found in tonsil SCC tissues. Furthermore, our findings suggest that MMP-9 expression might be a useful prognostic factor.     

慢性鼻窦炎相关内在型分类及血液标志物的研究进展

目的随着慢性鼻窦炎(CRS)内在型及血液标志物的相关研究不断取得进展,CRS的治疗已经开始向精准医学时代迈进。本文总结了CRS的内在型分类及CRS内在型与血液标志物的关系,并重点介绍了以II型炎症反应血液标志物为首的CRS血液标志物目前在CRS中的研究进展。我们期望找到更符合临床需要的血液标志物,为建立相应的CRS内在型分型提供依据,以便更好地指导CRS的个性化治疗及预后判断。     

Regulation of transforming growth factor-β1 activation and expression in the tissue remodeling involved in chronic rhinosinusitis

Transforming growth factor-β1 (TGF-β1) plays a key role in the tissue remodeling processes involved in chronic rhinosinusitis (CRS), with the biological functions of secreted TGF-β1 regulated by multiple proteins. Among these regulators, latency-associated peptide and latent TGF-β-binding protein inhibit TGF-β1 function, whereas different proteases and integrins activate it. Progress in understanding the factors responsible for the bioactivity and expression of TGF-β1 has revealed that the dysregulation of TGF-β1 activation and expression is closely associated with the chronic respiratory inflammatory diseases involved in CRS. This review of the regulation of TGF-β1 activation and expression provides insight into the mechanism responsible for the different CRS subtypes, which will help further the investigation of novel therapy targets for the treatment of CRS.     

Extracellular matrix as a scaffold for laryngeal reconstruction

Porcine-derived xenogeneic extracellular matrix (ECM) has been successfully used as a scaffold for tissue repair and reconstruction in numerous preclinical animal studies and human applications. These scaffolds are completely and rapidly degraded and replaced by host-derived tissues that frequently mimic the original tissue composition and architecture. The purpose of the present study was to examine the morphology of ECM scaffolds after their use for laryngeal reconstruction. Thirty adult female dogs were subjected to a partial hemilaryngectomy. The right thyroid cartilage and vocal fold were replaced with ECM scaffold, and the dogs were painlessly sacrificed from 1 week to 12 months after surgery. Histologic examination of the reconstructed tissue showed the presence of a simple squamous epithelial lining, organized glandular structures within the submucosa, reconstructed thyroid cartilage, and bundles of skeletal muscle by 3 months after surgery. We conclude that ECM scaffolds are promising templates for constructive remodeling of laryngeal tissue.     

YKL-40与慢性鼻-鼻窦炎组织重构的相关性探讨

YKL-40是哺乳类动物类几丁质酶蛋白家族的一员。近年来的多项研究则进一步表明YKL-40在哮喘、关节炎等多种炎性疾病中表达升高,并在疾病的组织重塑中发挥了重要作用。慢性鼻-鼻窦炎(CRS)是鼻-鼻窦黏膜的持续性炎症,主要表现为鼻塞、黏性分泌物、鼻黏膜充血和后鼻滴漏,次要表现为面部压迫感和头痛。CRS的发病机制十分复杂,目前已知炎性反应和组织重构在病理进程中发挥重要作用。在CRS临床分型、诊断和治疗等诸多方面尚存在争议,目前临床上主要依靠鼻内镜检查及CT扫描进行分型诊断,缺乏能在病理生理机制及分子细胞水平深入反映疾病特征的标志物。结合文献探讨YKL-40与慢性鼻窦炎组织重构和炎性反应的相关性以及作为血清标志物的可能性。     

症状、CT和鼻声反射在慢性鼻窦炎组织重构诊断中的意义

目的探讨鼻塞症状、CT扫描Lund-Mackay评分和鼻声反射测量鼻黏膜充血指数与慢性鼻及鼻窦炎(chronic rhinosinusitis,CRS)组织重构程度之间的相关性,探讨三者在CRS组织重构诊断中的意义。方法选取CRS患者43例,应用视觉模拟评分(visual analogous scale,VAS)系统评价鼻塞症状;Lund- Mackay平分系统评价鼻窦CT扫描结果;鼻声反射测量获取鼻黏膜充血指数;钩突黏膜组织标本行鼻黏膜纤维化程度评分。应用统计学方法对其相关性进行分析。结果鼻塞症状严重程度与鼻黏膜纤维化程度之间无明显相关性(r=-0.046,P=0.77);CT评分与黏膜组织纤维化评分之间无相关性(r=0.132,P=0.40);鼻黏膜纤维化程度与鼻黏膜充血指数之间呈负相关(r=-0.348, P=0.022)。结论鼻黏膜充血指数能够反映病变黏膜的组织重构程度,辅助症状与CT检查指导CRS治疗策略。     

慢性鼻-鼻窦炎CT筛窦分型组织病理学与预后相关性

目的 观察评价慢性鼻-鼻窦炎(chronic rhinosinusitis,CRS)CT筛窦分型的组织病理学特点及其与预后的关系.方法 回顾性分析112例CRS患者,按术前轴位鼻窦CT进行筛窦分型;观察筛窦标本骨质病理学改变,并对筛窦骨质重塑活性进行评分;采用Lund和Kennedy鼻内镜评分评价预后;分析不同CT筛窦分型间筛窦骨质组织病理评分和鼻内镜评分的差异以及骨质组织病理评分和鼻内镜评分的相关性.结果 Ⅲ型(骨质增生型)25例,占22.3%;Ⅱ型(空泡型)44例,占39.35;Ⅰ型(蜂窝型)43例,占38.4%.Ⅲ型骨组织病理改变程度和术后随访鼻内镜评分分别与Ⅰ型和Ⅱ型间差异有统计学意义(P值分别为0.01,0.02).CBS患者的筛窦骨组织病理评分和术后鼻内镜评分有明显相关性(X2=9.78,P=0.002).结论 CBS的CT筛窦分型具有相应组织病理学基础;新骨形成或重塑是反映鼻窦疾病严重程度的重要指标,筛窦骨组织病变程度能够反映患者术后预后情况;CT筛窦分型对鼻内镜外科手术疗效的预测具有现实应用意义.