TLR-2和MMP-9在中耳胆脂瘤上皮中的表达

发布时间：2018-02-13 06:04

本文关键词： 胆脂瘤型中耳炎 TLR-2 MMP-9 发病机制　出处：《汕头大学》2010年硕士论文　论文类型：学位论文

【摘要】： 背景与目的胆脂瘤型中耳炎(Otitis media cholesteatoma)是慢性化脓性中耳炎的一种常见类型,在病理上表现为中耳腔内高度增生的角化鳞状上皮堆积和对周围骨质的破坏,在临床上表现为耳溢液、听力下降和耳鸣等。其中对颞骨的溶骨性破坏是胆脂瘤型中耳炎最重要的临床特征和病理生理学过程。就目前人类医学发展水平来说,只要病人被确诊为胆脂瘤型中耳炎,唯一切实有效阻止病变发展的方法就是手术治疗。在胆脂瘤的发病机制中,如果能够明确胆脂瘤型中耳炎发病时各种相关受体、细胞因子和各种酶对于该疾病发生发展的作用机理,然后制订相应的措施,比如开发利用相关受体的阻断剂、相关酶的抑制剂,那么,药物治疗和预防胆脂瘤型中耳炎就不再遥不可及。基于以上观点,目前国内外关于胆脂瘤的研究主要集中在发病机制上,虽然有各种发病学说,但是其确切的发病机制,迄今尚未清楚。其中TLR-2和MMP-9在胆脂瘤型中耳炎发病机制中,尤其在骨质破坏中所起的重要作用日益受到人们的关注。 Toll样受体( TLRs)是一类典型的模式识别受体(Pattern recognition receptor,PRR) ,一组与天然免疫密切相关的受体家族。TLRs家族中,TLR-2识别谱最广。基质金属蛋白酶(Matrix metalloproteinases ,MMPs)是一组在结构上具有极大同源性,并且具有很多共同生化性质的可降解细胞外基质的内肽酶的总称。MMP-9隶属于明胶酶,其作用底物主要有Ⅰ,Ⅲ,Ⅳ,Ⅴ型胶原以及明胶、纤维连接蛋白、弹力蛋白、蛋白聚糖等。国内外均分别有文献报道相对于正常外耳道皮肤,TLR-2和MMP-9在中耳胆脂瘤上皮中高表达。因此我们设想,TLR-2和MMP-9在胆脂瘤型中耳炎的发病机制中,尤其在骨质破坏中扮演重要的角色,两者存在着相互作用的关系:由于机体的免疫系统失调,导致TLR-2的内源性配体的表达,激活了TLR-2的信号传导途径,诱导局部产生多种促炎因子。其中的一些因子可引起或加重中耳组织的损伤和周围的骨质破坏,而一些因子上调MMPs的表达,进一步导致中耳组织的损伤和骨质破坏。方法选取符合纳入标准的汕头大学医学院第一附属医院耳鼻咽喉头颈外科2008年9月至2010年4月住院中耳胆脂瘤患者35例作为实验组,采集手术切除标本35份。同时选取行鼓膜修补术病人的外耳道皮肤10例做为对照组。所有的受检者实验前2周内均无全身或局部使用糖皮质激素及免疫制剂。所有标本经过处理(固定、包埋、切片等)后,用免疫组化法检测标本中TLR-2和MMP-9的表达情况。结果 1.中耳胆脂瘤组织中TLR-2的表达高于正常对照组,其差异有显著性意义(p 0.001)。 2.中耳胆脂瘤组织中MMP-9的表达高于正常对照组,其差异有显著性意义(p 0.001)。 3.中耳胆脂瘤组织中TLR-2与MMP-9的表达存在正相关关系(r=0.437,p 0.01)。结论 1. TLR-2在中耳胆脂瘤的骨质破坏机制中起到关键作用。 2. MMP-9在中耳胆脂瘤的骨质破坏机制中起到关键作用。 3. TLR-2与MMP-9之间在中耳胆脂瘤的骨质破坏机制中存在相互作用,前者可能是后者的诱导因素。
[Abstract]:Background and purpose
Cholesteatoma (Otitis media cholesteatoma) is a common type of chronic suppurative otitis media in pathology, the middle ear cavity height hyperplasia of squamous epithelium accumulation and damage to the surrounding bone, clinically as otorrhea, hearing loss and tinnitus. The temporal bone osteolytic destruction is the process of the clinical features and pathophysiology of cholesteatoma. The most important is the current level of human medicine development, as long as the patient was diagnosed as cholesteatoma, the only effective method to prevent the development of disease is surgery. In the pathogenesis of cholesteatoma, if can clear cholesteatoma pathogenesis related receptor inflammation, cytokines and enzymes for the mechanism of the occurrence and development of the disease, and then formulate corresponding measures, such as the development and utilization of related receptor blocking agent, phase Close the enzyme inhibitor, so, drug treatment and prevention of cholesteatoma otitis media is no longer out of reach. Based on the above point of view, the current research on cholesteatoma abroad mainly focus on the pathogenesis of the disease, although there are a variety of etiology, but its exact pathogenesis is not clear. Up to now, including TLR-2 and MMP-9 in the pathogenesis of cholesteatoma otitis media, especially in plays an important role in bone destruction is attracting more and more attention.
Toll like receptor (TLRs) is a kind of typical pattern recognition receptors (Pattern, recognition receptor, PRR), a group of closely related with the innate immune receptor family of.TLRs family, TLR-2 identification of the broadest spectrum. Matrix metalloproteinases (Matrix metalloproteinases MMPs) is a group in the structure has great homology within the peptide the enzyme and having the extracellular matrix degradation of many common biochemical properties of the general.MMP-9 belongs to the substrate of gelatinase, mainly I, III, IV, V collagen and gelatin, fibronectin, elastin and proteoglycans.
Both at home and abroad are reported relative to normal canal skin, TLR-2 and the high expression of MMP-9 in middle ear cholesteatoma. So we assume that TLR-2 and MMP-9 in the pathogenesis of cholesteatoma, especially play an important role in bone destruction, there is an interaction between the immune system disorders due to: the resulting expression of the endogenous ligand of TLR-2, activation of TLR-2 signaling pathway induced by local produce proinflammatory cytokines. Various damage of bone mass of some factor which can cause or aggravate the middle ear tissue damage and the surrounding, and some factors of the increased expression of MMPs, resulting in further damage of the middle ear tissue and bone.
Method
Selected into the hospital standard First Affiliated Hospital of Shantou University Medical College of Otolaryngology Head and neck surgery from September 2008 to April 2010, 35 cases of cholesteatoma patients as the experimental group, collected resected specimens of 35 copies. At the same time to select 10 cases of myringoplasty for patients with external auditory canal skin as control group. 2 weeks without the use of systemic or topical corticosteroids hormone and immune agents of all subjects before the experiment. All specimens after treatment (fixation, embedding, sectioning), the expression of TLR-2 and MMP-9 were detected by immunohistochemical method.
Result
The expression of TLR-2 in 1. middle ear cholesteatoma tissues was higher than that in the normal control group, and the difference was significant (P 0.001).
The expression of MMP-9 in 2. middle ear cholesteatoma tissues was higher than that in the normal control group, and the difference was significant (P 0.001).
There was a positive correlation between the expression of TLR-2 and MMP-9 in 3. middle ear cholesteatoma tissues (r=0.437, P 0.01).
conclusion
1. TLR-2 plays a key role in the mechanism of bone destruction in the middle ear cholesteatoma.
2. MMP-9 plays a key role in the mechanism of bone destruction in the middle ear cholesteatoma.
There is a interaction between 3. TLR-2 and MMP-9 in the mechanism of bone destruction in the middle ear cholesteatoma, the former may be the inducing factor of the latter.

【学位授予单位】：汕头大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R764

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