急/慢性睡眠剥夺对颞下颌关节系统的作用效应及机理研究

People are suffering greatly from daily stress, such as fast pace of modern life and intense social competition, which make sleep deprivation related disorders gradually increase year by year. It has been demonstrated that sleep deprivation can cause hormone, neurotransmitter changes, which could be closely related to the pathogenesis of temporomandibular joint disorders. Our preliminary studies have confirmed that sleep deprivation can cause changes in microstructure of masseter and synovial cartilage of temporomandibular joint, such as pain-related factors, inflammatory cytokines and NF-kb pathway. However, what kind of impact on the temporomandibular joint system muscle, cartilage and bone could be induced by acute and chronic sleepdeprivation? Would it lead temporomandibular joint pain? This study was designed to establish animal models with acute/chronic sleep deprivation simulating human sleep disorder, observe the structural, metabolic and functional alterations of masticatory muscle and temporomandibular joint in rats by behavioral, molecular biological and physiological approaches and systematically illustrate the changing pattern of the motor function of stomatognathic system following sleep deprivation, aiming at providing novel experimental evidence for analysis of the pathogenesis and mechanism of sleep disorder-induced stomatognathic system illnesses.

快节奏的现代生活和激烈的社会竞争使人们每天承受着复杂的应激事件，由此引发的睡眠剥夺相关疾患呈逐年上升趋势，严重影响到人们的健康。国内外临床研究证实，睡眠剥夺可引起体内激素、神经递质的变化，可能与颞颌关节紊乱疾病的发病密切相关。本课题组前期发现，睡眠剥夺可引起咬肌微结构、颞颌关节滑膜软骨内疼痛相关因子、炎性因子和NF-kb通路等发生改变。但急、慢性睡眠剥夺对颞颌关节系统中肌肉、软骨和骨会产生何种影响？是否会引起颞颌关节疼痛？目前尚无系统性研究报道。针对上述问题，本项目拟在前期研究的基础上，观察急、慢性睡眠剥夺后大鼠颞颌关节系统的结构和功能改变，分析睡眠剥夺参与肌肉、关节软骨和骨改建的作用机制，探讨睡眠剥夺致颞下颌关节疼痛的可能分子机制。为颞下颌关节紊乱疾病的发病机制研究提供新的实验依据，具有十分重要的理论意义和潜在应用价值。

睡眠剥夺是指人因环境或自身原因丧失了所需要睡眠量的一种过程和状态。近年来，由睡眠剥夺引发的相关疾患呈逐渐升高趋势，严重影响到人们的生活和健康。尤其在现代快节奏的生活和激烈的社会竞争下，这方面的问题显得尤为突出，其已发展成为当前亟需解决的严重社会问题。目前关于睡眠剥夺的研究主要集中在学习记忆、免疫功能和认知行为等方面，但越来越多的临床和基础研究证实睡眠剥夺在其他系统性疾病的发生、发展中也发挥着作用。近期临床研究发现，睡眠剥夺可引起体内激素、神经递质的变化，在颞下颌关节紊乱（Temporomandibular Disorders，TMD)病的发病中可能起着重要作用。课题组本项目的资助下主要从以下几个方面做了深入研究：.1、.建立了大鼠慢性睡眠剥夺动物模型，运用旷场试验和血清中相关指标对大鼠慢性睡眠剥夺动物模型进行评价。.2、.运用光镜和扫描电镜检测了慢性睡眠剥夺对大鼠颞下颌关节髁突软骨的组织学影响。.3、.慢性睡眠剥夺后大鼠髁突软骨Pi3k/Akt通路凋亡相关因子表达异常。.4、.慢性睡眠剥夺后大鼠颞下颌关节ERK信号通路的影响；结果说明睡眠剥夺后大鼠TMJ髁突软骨中P-ERK被活化，MMP-1、MMP-3和MMP-13的表达升高。ERK抑制剂U0126能够抑制P-ERK的活化以及MMP-1、MMP-3和MMP-13的表达。同时，在实验中我们也发现关节腔内注射ERK抑制剂U0126后，TMJ的病理性变化有所缓解。.5、.慢性睡眠剥夺后骨桥蛋白调节NF-kappaB通路对颞下颌关节有种要影响；.6、.慢性睡眠剥夺后大鼠颞下颌关节骨软骨有血管新生现象；初步明确了VEGF调控Dll4和p-E RK1/2信号通路参与到髁突软骨血管新生过程中的机制。.本研究初步阐述了急、慢性睡眠剥夺后颞下颌关节的变化规律，为深入研究睡眠剥夺所致 TMD 的发病机理和防治措施提供新的实验依据。