本文關(guān)鍵詞： 膽脂瘤型中耳炎 TLR-2 MMP-9 發(fā)病機(jī)制　出處：《汕頭大學(xué)》2010年碩士論文　論文類(lèi)型：學(xué)位論文

【摘要】： 背景與目的 膽脂瘤型中耳炎(Otitis media cholesteatoma)是慢性化膿性中耳炎的一種常見(jiàn)類(lèi)型,在病理上表現(xiàn)為中耳腔內(nèi)高度增生的角化鱗狀上皮堆積和對(duì)周?chē)琴|(zhì)的破壞,在臨床上表現(xiàn)為耳溢液、聽(tīng)力下降和耳鳴等。其中對(duì)顳骨的溶骨性破壞是膽脂瘤型中耳炎最重要的臨床特征和病理生理學(xué)過(guò)程。就目前人類(lèi)醫(yī)學(xué)發(fā)展水平來(lái)說(shuō),只要病人被確診為膽脂瘤型中耳炎,唯一切實(shí)有效阻止病變發(fā)展的方法就是手術(shù)治療。在膽脂瘤的發(fā)病機(jī)制中,如果能夠明確膽脂瘤型中耳炎發(fā)病時(shí)各種相關(guān)受體、細(xì)胞因子和各種酶對(duì)于該疾病發(fā)生發(fā)展的作用機(jī)理,然后制訂相應(yīng)的措施,比如開(kāi)發(fā)利用相關(guān)受體的阻斷劑、相關(guān)酶的抑制劑,那么,藥物治療和預(yù)防膽脂瘤型中耳炎就不再遙不可及�；谝陨嫌^點(diǎn),目前國(guó)內(nèi)外關(guān)于膽脂瘤的研究主要集中在發(fā)病機(jī)制上,雖然有各種發(fā)病學(xué)說(shuō),但是其確切的發(fā)病機(jī)制,迄今尚未清楚。其中TLR-2和MMP-9在膽脂瘤型中耳炎發(fā)病機(jī)制中,尤其在骨質(zhì)破壞中所起的重要作用日益受到人們的關(guān)注。 Toll樣受體( TLRs)是一類(lèi)典型的模式識(shí)別受體(Pattern recognition receptor,PRR) ,一組與天然免疫密切相關(guān)的受體家族。TLRs家族中,TLR-2識(shí)別譜最廣。基質(zhì)金屬蛋白酶(Matrix metalloproteinases ,MMPs)是一組在結(jié)構(gòu)上具有極大同源性,并且具有很多共同生化性質(zhì)的可降解細(xì)胞外基質(zhì)的內(nèi)肽酶的總稱(chēng)。MMP-9隸屬于明膠酶,其作用底物主要有Ⅰ,Ⅲ,Ⅳ,Ⅴ型膠原以及明膠、纖維連接蛋白、彈力蛋白、蛋白聚糖等。 國(guó)內(nèi)外均分別有文獻(xiàn)報(bào)道相對(duì)于正常外耳道皮膚,TLR-2和MMP-9在中耳膽脂瘤上皮中高表達(dá)。因此我們?cè)O(shè)想,TLR-2和MMP-9在膽脂瘤型中耳炎的發(fā)病機(jī)制中,尤其在骨質(zhì)破壞中扮演重要的角色,兩者存在著相互作用的關(guān)系:由于機(jī)體的免疫系統(tǒng)失調(diào),導(dǎo)致TLR-2的內(nèi)源性配體的表達(dá),激活了TLR-2的信號(hào)傳導(dǎo)途徑,誘導(dǎo)局部產(chǎn)生多種促炎因子。其中的一些因子可引起或加重中耳組織的損傷和周?chē)墓琴|(zhì)破壞,而一些因子上調(diào)MMPs的表達(dá),進(jìn)一步導(dǎo)致中耳組織的損傷和骨質(zhì)破壞。 方法 選取符合納入標(biāo)準(zhǔn)的汕頭大學(xué)醫(yī)學(xué)院第一附屬醫(yī)院耳鼻咽喉頭頸外科2008年9月至2010年4月住院中耳膽脂瘤患者35例作為實(shí)驗(yàn)組,采集手術(shù)切除標(biāo)本35份。同時(shí)選取行鼓膜修補(bǔ)術(shù)病人的外耳道皮膚10例做為對(duì)照組。所有的受檢者實(shí)驗(yàn)前2周內(nèi)均無(wú)全身或局部使用糖皮質(zhì)激素及免疫制劑。所有標(biāo)本經(jīng)過(guò)處理(固定、包埋、切片等)后,用免疫組化法檢測(cè)標(biāo)本中TLR-2和MMP-9的表達(dá)情況。 結(jié)果 1.中耳膽脂瘤組織中TLR-2的表達(dá)高于正常對(duì)照組,其差異有顯著性意義(p 0.001)。 2.中耳膽脂瘤組織中MMP-9的表達(dá)高于正常對(duì)照組,其差異有顯著性意義(p 0.001)。 3.中耳膽脂瘤組織中TLR-2與MMP-9的表達(dá)存在正相關(guān)關(guān)系(r=0.437,p 0.01)。 結(jié)論 1. TLR-2在中耳膽脂瘤的骨質(zhì)破壞機(jī)制中起到關(guān)鍵作用。 2. MMP-9在中耳膽脂瘤的骨質(zhì)破壞機(jī)制中起到關(guān)鍵作用。 3. TLR-2與MMP-9之間在中耳膽脂瘤的骨質(zhì)破壞機(jī)制中存在相互作用,前者可能是后者的誘導(dǎo)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.

【學(xué)位授予單位】：汕頭大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2010
【分類(lèi)號(hào)】：R764

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