【作者】 程勇；

【导师】 边专； 龙星；

【作者基本信息】 武汉大学 ， 口腔临床医学， 2004， 博士

【摘要】 颞下颌关节是一个独特的双侧联动关节，在人们的日常生活中发挥至关重要的作用。颞下颌关节盘前移位(Anterior Disc Displacement of Temporomandi-bular Joint)是指关节盘与关节窝、关节结节以及髁突的相对位置发生改变。在正常情况下，颞下颌关节盘位于关节窝、关节结节与髁突之间，关节盘后带的中点位于髁突横嵴顶上。关节盘与髁突内外极之间有坚固的附着和韧带维持。关节盘外观呈双凹形，分前、中、后三个带，其中中间带最薄，其凹面正好与关节结节、髁突相对应，所以在正常闭口位情况下，关节盘无明显前移位。如果关节盘前移位，可出现不同程度颞下颌关节功能障碍。据统计人群中，出现颞下颌关节功能障碍者占25～50％。说明颞下颌关节盘前移位是临床上的一种常见、多发病。然而至今为止，颞下颌关节盘前移位的病因和发病机理尚不清楚，关节盘前移位与关节疼痛，下颌功能障碍以及颞下颌关节滑膜炎、骨关节病等临床症状及颞下颌关节紊乱病分类之间的关系还存在争议。 颞下颌关节是滑膜关节。颞下颌关节滑膜覆盖着关节囊的关节腔面，它由两层组织构成，第一层为贴近关节腔的内衬细胞层，称为滑膜内膜；第二层为支持层，称为滑膜内膜下组织。滑膜内膜细胞一般分为A型和B型两类，B型细胞能合成和修饰所有的细胞外基质(Extracellular matrix ECM)和滑液成份，而A型细胞主要处理从关节腔和ECM中产生的代谢废用物质。滑膜组织在颞下颌关节紊乱病的发生、发展以及转归过程中，具有重要的作用。但是近年来，对颞下颌关节盘前移位的动物实验发生、发展以及转归过程的研究，较多地观察了关节盘、髁突软骨病理性改变，而对滑膜组织病理性改变较少报道。因此建立一个颞下颌关节关节盘前移位的动物模型，系统、全面研究颞下颌关节关节盘前移位发生、发展及转归演变过程中滑膜组织的病理性改变具有重要义。本研究的目的是建立一个兔颖下领关节盘前移位的动物模型，并从肉眼、X线、光镜、电镜以及组织化学水平系统地观察关节盘前移位滑膜组织病理变化过程，为进一步阐述颗下领关节盘前移位发病机制打下基础。 本研究分五部分，第一部分:颖下领关节盘前移位的动物实验研究，第二部分:颗下领关节盘前移位滑膜的组织学改变。第三部分:颖下领关节盘前移位滑膜组织超微结构改变。第四部分:一氧化氮合酶在兔颖下领关节盘前移位滑膜组织中的表达改变。第五部分:血管内皮生长因子在兔颖下领关节盘前移位滑膜组织中的表达改变。 第一、二、三部分:24只4一6月龄大耳白兔进行了动物实验。根据翼外肌牵拉产生人类关节盘前移位的原理，应用手术方法使20只大耳白兔一侧关节盘前移位，并保留关节盘与关节腔的完整性。另一侧关节作为手术对照组，其余4只大耳白兔作为正常对照组。关节盘前移位术后1、2、4、8周，分别取出关节组织。进行肉眼、X线、组织病理学研究及透射电镜观察。 研究结果表明，实验动物术后1周及2周组:1侧关节盘前外侧移位，2侧关节盘穿孔。术后4周组:2侧关节盘前外侧移位。术后8周组:2侧关节盘前外侧移位。 关节X线片显示实验动物术后关节间隙狭窄和消失，裸突表面不平，骨质破坏，增生，关节结节边界不清。 组织病理学研究显示实验动物术后，早期滑膜细胞增生，滑膜组织增厚甚至形成突起且朝向关节腔内。滑膜下组织致密，血管扩张，出血，血管数量增多，血管周围可见炎性细胞浸润，可见纤维样结构物质沉积。晚期部分表现滑膜细胞增生，部分区域出现脂肪样变性或玻璃样变性，部分表现滑膜细胞消失。滑膜下血管出现闭塞甚至纤维变性，血管出现闭塞，血管减少，滑膜下甚至出现囊性变(假囊形成)，滑膜下组织致密。最后，滑膜组织消失而形成盘样组织改变。 超微结构透射电镜观察显示实验动物术后，早期滑膜细胞表面有一层电子密度高的物质，并且滑膜细胞胞浆细胞器结构不清。晚期滑膜细胞结构仍模糊。少数术后4周出现正常滑膜细胞，但细胞周围胶原纤维较多。 第四、五部分主要是应用免疫组织化学的方法，研究一氧化氮合酶及血管内皮生长 II因子在兔颖下领关节盘前移位滑膜组织中的表达改变。研究发现一氧化氮合酶及血管内皮生长因子主要出现在滑膜细胞、滑膜下血管内皮细胞及成纤维细胞胞浆中，并且实验动物术后，一氧化氮合酶及血管内皮生长因子在上述细胞中的表达均比正常对照组与手术对照组增强，显示为强阳性或阳性。 总之，本研究结果表明颗下领关节盘前移位滑膜组织的病理性改变明显。由早期滑膜组织增生，血管扩张，血管数量增多，逐渐演变到滑膜下组织致密，滑膜下血管出现闭塞，血管减少，滑膜组织出现变性，直至滑膜组织消失而形成盘样组织改变。同时，本研究结果表明一氧化氮合酶及血管内皮生长因子在颖下领关节盘前移位滑膜组织的病理性演变过程中，发挥一定的作用。通过本研究结果认为临床上，应对颖下领关节盘前移位的患者，进行早期治疗，防止滑膜组织的病理性改变逐渐加重。因此，对临床工作具有重要的指导作用。更多还原

【Abstract】 Temporomandibular joint (TMJ) is a unique diarthroidal joint and crucial to the everyday functioning of modern man. Anterior Disc displacement of temporomandibular Joint refers to the relative changes of the postion amonge joint disc and glenoid fossa and articular eminence of the temporal bone and joint condyle .In the normal position joint disc lies between gleniod fossa , articular eminence and joint condyle. Center of posterior band of joint disc is right above axial rigde of condyle. There are tight attachments and sustainment from the ligments. The joint disc is the biconcave contour, and is divided into three sections: anterior band, center one and posterior one,center band is the thinnest part ,which is directly correspondent to the joint condyle and articular eminence .Therefore, there is no significant displacement of the disc in the normal open mouth position. There are TMJ dysfunctions to some degree after the disc displacement. It is statistical that the dysfunction of the joint by 25-30% among the people, which demonstrate that Anterior Disc displacement of TMJ is common disease with high frequency. But the etiology and pathogenesis of Anterior Disc displacement of TMJ remain an enigma and relationship of Anterior Disc displacement of TMJ to pain, mandibular dysfunction and osteoarthrosis is controversial.TMJ is synovial joint, of which synovial membrane covers surface of joint cavity ,and consists of two layers of soft tissue.The first layer is lining cell layer within the cavity, the second layer is sustainable layer .Synovial lining cell divided into type A and type B, that type B cells can synthesis and modify all ECM (Extracellular matrix ECM) and synovial fluid ,and type A cells mainly deal with metabismic wastes from joint cavity and ECM. The synovialtissue is predominantly important in the initial, progressive and transferring processes of TMD. But recently most of animal model experiments focused on the researches of joint disc and cartilage without dealing with the synovial membrane. So our experiments construct an animal model of Anterior Disc displacement of TMJ, and systemic study pathologic changes and significance in the initial, progressive and transferring processes of Anterior Disc displacement. The objective of these researches is to build animal model, and to observe the pathologic process of the synovial membrane tissue of Anterior Disc displacement of TMJ by nude eyes, x-ray, microscope, eletromicroscope and histochemistry methods, which can for a base for further explanation of pathologic process in Anterior Disc displacement of TMJ.These researches can be indivded into six parts:First, Study on synovial membrane the animal model of Anterior Disc displacement of TMJ; Second, Histological changes of synovial membrane in the animal model of Anterior Disc displacement of TMJ; Third, Ultrastructure histological changes of synovial membrane in the animal model of Anterior Disc displacement of TMJ; Forth, Expressions of iNOS in the synovial membrane of the animal model of Anterior Disc displacement of TMJ; Fifth, Expressions of VEGF in the synovial membrane of the animal model of Anterior Disc displacement of TMJ.In the first three parts, twenty-four young adult white rabbits (4 to 6 months) were used in this study. The disc was surgically displayed anteriorly, like the lateral pterygoid muscle traction generating human ADD, in one side joint in each of 20 rabbits. In this way, the joint space and disc attachment were left intact. The other joints were served as surgical controls and 4 rabbits without any disease were regarded as normal controls. The tissues in joints were took out en bloc 1, 2, 4 and 8 weeks after induction of ADD according to the experimental groups. The tissue were studied radiographically and histologically under X rays and transmission electron microscope.The results under the unaided eyes showed that different damage occurred with time,including disc perforation in two cases at 2 weeks after induction, anterior-lateral discdisplacement in 2 c更多还原