慢性睡眠剥夺对颞下颌关节微结构的影响

目的:研究慢性睡眠障碍对大鼠颞下颌关节微结构的影响。方法:采用改良多平台法(MMPM)建立睡眠剥夺模型,将90只Wistar大鼠随机分为3组(n=30),分别为小平台组、网格组和对照组。小平台组和网格组大鼠接受每天18 h的睡眠剥夺和6 h间歇期(10:00—16:00),间歇期大鼠正常笼养。实验第7、14和21天时分别行动物行为学观察、旷场试验和动物血浆检测,并通过HE染色和扫描电镜观察颞下颌关节微结构的变化。结果:与对照组和网格组相比,小平台组大鼠血清促肾上腺激素(ACTH)和皮质醇(CORT)水平均增高(P<0.05),髁突软骨HE染色显示软骨细胞层次及厚度改变;扫描电镜结果显示关节盘表面纤维排列松散。结论:慢性睡眠障碍可能导致颞下颌关节微结构发生病理性改变。     

睡眠剥夺对大鼠行为学及咀嚼肌肌电图的影响

目的：颞下颌关节紊乱病是口腔科的一种常见病和多发病,精神心理因素是颞下颌关节紊乱病的一个主要病因。本文通过观察睡眠剥夺对大鼠行为学及咀嚼肌肌电图的影响,探讨睡眠剥夺在颞下颌关节紊乱病发病中的作用。方法：35只Wistar大鼠,随机分为5组：睡眠剥夺1d组、5d组、9d组、正常对照组和大平台对照组。采用改良多平台睡眠剥夺法（modified multiple plat—formmethod,MMPM）建立大鼠SD模型,观察大鼠行为学及咀嚼肌肌电图的变化。结果：睡眠剥夺1d组和5d组在旷场实验水平得分和垂直得分上均高于对照组,而睡眠剥夺9d组均低于对照组;睡眠剥夺1d、5d和9d组在松弛状态和紧咬状态时颞肌前后束及咬肌的电位均明显高于对照组,且两侧无明显差别,同时,睡眠剥夺组双侧颞肌和咬肌的肌电图静息期较对照组显著延长。结论：睡眠剥夺可使大鼠行为学发生改变并对咀嚼肌肌电图造成影响,这可能是颞下颌关节紊乱病的病因之一,为我们对颞下颌关节紊乱病的预防和治疗提供了一定的理论指导。     

慢性睡眠限制状态下大鼠髁突软骨MMP-1,MMP-13表达的变化

目的:探讨MMP-1,MMP-13在慢性睡眠限制引起大鼠髁突软骨结构变化中的表达变化及作用。方法:180只雄性Wistar大鼠随机分为3组(n=60):慢性睡眠限制组(CSR)、大平台组(LC)、笼养组(CON)。每组根据试验时间不同分别分为3个亚组(n=20):7天(7D)、14天(14D)、21天(21D)组。参考改良多平台法(MMPM)建立大鼠的慢性睡眠限制模型。通过HE染色观察大鼠髁突软骨的结构变化。通过免疫组化和实时定量PCR分别检测MMP-1和MMP-13的蛋白水平及m RNA水平的表达变化。结果:HE染色和扫描电镜结果显示,CSR组的大鼠髁突软骨出现了病理性的改变。与CON和LC组比较,CSR组MMP-1和MMP-13的m RNA转录和蛋白表达水平明显升高(P0.05)。结论:慢性睡眠限制能够引起大鼠颞下颌关节髁突软骨的病理性变化。MMP-1和MMP-13的表达水平的变化可能在大鼠髁突软骨病理性改变中起关键作用。     

颞下颌关节紊乱患者关节液中MMP-3 和MMP-9表达的临床意义

目的:研究颞下颌关节紊乱(TMD)患者关节液中基质金属蛋白酶-3(MMP-3)和基质金属蛋白酶-9(MMP-9)水平变化及临床意义,为临床诊疗提供依据。方法:选取2013年4月到2016年4月我院收治的TMD患者60例,根据患者病变程度分为炎性疾病组(n=21例)、结构紊乱组(n=18例)、骨关节病组(n=21例),另选取同期健康志愿者30例为对照组采集研究者的关节液标本并应用双抗体夹心酶联免疫法检测关节液标本中MMP-3和MMP-9的水平。结果:骨关节病组MMP-3和MMP-9水平显著高于结构紊乱组、炎性疾病组和对照组,结构紊乱组、炎性疾病组显著高于对照组,比较差异具有统计学意义(P0.05),结构紊乱组与炎性疾病组比较差异无统计学意义(P0.05)。结论:关节液中MMP-3和MMP-9水平随着TMD病变程度增加而明显升高,能在一定程度上反应颞下颌关节病严重程度。     

应激与颞下颌关节紊乱病研究新进展

颞下颌关节紊乱病是慢性面部疼痛最常见的诱因,常常与躯体和心理主诉症状密切联系,包括疲劳,睡眠失调,焦虑和抑郁等。即使未发现任何能够合理解释疼痛原因的时候,健康专业人士也常常忽略疼痛感受的主观性。从严格的生物医学角度来讲,对疼痛的这种理解是不科学的。本文的主要目的是通过查阅近年来大量的研究文献资料,发现应激引起疼痛感觉的生物学途径以及导致颞下颌关节紊乱的原因。研究发现下丘脑-垂体-肾上腺轴、5-羟色胺和阿片样物质通路都与颌面部疼痛的发病密切相关,同时也提出了未来可能使用的治疗方法。同时,也希望本文能把与疼痛学科差别较大的口腔医学融入到需要多学科合作的颞下颌关节紊乱的诊断和治疗中,从科学角度提高对该病的临床诊疗效率。     

应激与颞下颌关节紊乱病研究新进展

颞下颌关节紊乱病是慢性面部疼痛最常见的诱因,常常与躯体和心理主诉症状密切联系,包括疲劳,睡眠失调,焦虑和抑郁等。即使未发现任何能够合理解释疼痛原因的时候,健康专业人士也常常忽略疼痛感受的主观性。从严格的生物医学角度来讲,对疼痛的这种理解是不科学的。本文的主要目的是通过查阅近年来大量的研究文献资料,发现应激引起疼痛感觉的生物学途径以及导致颞下颌关节紊乱的原因。研究发现下丘脑-垂体-肾上腺轴、5-羟色胺和阿片样物质通路都与颌面部疼痛的发病密切相关,同时也提出了未来可能使用的治疗方法。同时,也希望本文能把与疼痛学科差别较大的口腔医学融入到需要多学科合作的颞下颌关节紊乱的诊断和治疗中,从科学角度提高对该病的临床诊疗效率。     

牵张成骨联合正颌正畸技术治疗颞下颌关节强直的效果分析

目的：探讨联合采用牵张成骨以及正颌正畸技术治疗颞下颌关节强直的效果。方法：选取我院收治的50 例颞下颌关节强直 继发小下颌畸形患者,根据不同的手术方式将其分为观察组以及对照组,对照组仅采取正颌正畸治疗,观察组一期通过关节成形 术解除关节强直,完成正畸治疗后,二期采用牵张成骨以及颏成形术矫治小下颌畸形伴随OSAHS,术后进行8-35 月的随访,评价 治疗效果。结果：观察组的牵张距离、颏前移距离以及术后张口度均明显大于对照组,且最大张口度均大于20 mm,平均最大张口 度由术前的3.2 mm增加至术后的36.7 mm,P<0.05,观察组术后能够恢复正常咬合关系和咀嚼功能,两组患者术后的平均睡眠紊 乱指数（AH1）、LAST、后气道间隙（PAS）以及SNB 角度比较有统计学差异,P<0.05,观察组术后患者的OSAHS 症状均得到显著 的改善,未出现OSAHS复发情况。结论：牵张成骨联合正颌正畸技术治疗颞下颌关节强直可以获得满意的效果,可以很好的矫治 牙额面畸形,且能够有效改善伴发的OSAHS 症状。     

MMP-2、MMP-3、MMP-9、TIMP-3及Col-Ⅱ因子在兔软骨细胞损伤后的表达变化

检测MMP-2、MMP-3、MMP-9、TIMP-3及Ⅱ型胶原细胞外基质因子在正常兔关节软骨细胞和划伤后不同时间点的表达变化。在无菌条件下获取兔膝关节软骨细胞,原代体外培养软骨细胞,六孔板内制备细胞损伤模型。用显微镜观察正常细胞和损伤后1 d、3 d和7 d 3个时间点的软骨细胞增殖情况。采用实时PCR检测正常软骨细胞和损伤后1 d、3 d和7 d 3个时间点的基质金属蛋白酶-2、3和9,基质金属蛋白酶抑制物-3及Ⅱ型胶原的m RNA的表达水平。成功分离软骨,经原代培养后成功建立损伤细胞模型。MMP-2损伤后第1天与正常组相比升高,第3天时下降,第7天明显水平最高。与正常组相比,MMP-3在细胞损伤后第1天表达明显下降,随后第3天逐渐下降,第7天与第3天未见明显变化。MMP-9划伤后第1天比正常组升高,第3天上升至最高水平,第7天下降。TIMP-3基因在损伤后第1天与正常组相比明显下降,随后第3天稍有升高,第7天水平最低。Ⅱ型胶原划伤后第1天与正常组相比明显升高,随后第3天呈下降趋势接近于正常组,第7天又呈上升趋势。MMP-2、MMP-3、MMP-9、TIMP-3因子和Ⅱ型胶原在细胞损伤后的不同时间点有不同的表达行为,这可为调节细胞外基质基因治疗关节软骨损伤选择合适的靶基因和时间窗提供实验依据。     

丁苯酞对睡眠剥夺大鼠额叶小胶质细胞活化的影响*

目的: 探讨丁苯酞对慢性睡眠剥夺后大鼠脑部额叶小胶质细胞活化及炎症因子的影响。方法: 本实验共分为4组(n＝8):空白对照组、大平台对照组、慢性睡眠剥夺组、丁苯酞干预组。慢性睡眠剥夺组和丁苯酞干预组采用改良多平台睡眠剥夺法建立大鼠慢性睡眠剥夺模型,对大鼠进行每日18 h,连续28 d的睡眠剥夺。在这28 d内,空白对照组大鼠不进行睡眠干预,大平台对照组大鼠放于大平台箱内。丁苯酞干预组在睡眠剥夺28 d结束后按100 mg/kg腹腔注射丁苯酞针剂,每日1次,共14 d,其他组大鼠在这14 d内腹腔注射同样剂量的生理盐水。腹腔注射结束后各组大鼠取脑组织,免疫组化检测额叶皮质离子钙接头分子(Iba-1)阳性细胞并计数,Western blot检测额叶诱导型一氧化氮合成酶(iNOS)、精氨酸酶1(Arg1)表达,实时定量PCR检测额叶白介素-1(IL-1)mRNA、IL-6 mRNA、肿瘤坏死因子-α(TNF-α) mRNA。结果: 与空白对照组、大平台对照组比较,慢性睡眠剥夺组额叶Iba-1阳性细胞体积增大伴细胞突起增多,且细胞数增加(P均＜0.05),iNOS和IL-1 mRNA、IL-6 mRNA、TNF-α mRNA表达增加,而Arg1表达减少(P均＜0.05);与慢性睡眠剥夺组比较,丁苯酞干预组额叶Iba-1细胞数减少(P＜ 0.05),iNOS和IL-1 mRNA、IL-6 mRNA、TNF-α mRNA表达减少(P均＜0.05)而Arg1表达无明显改变。结论: 丁苯酞可抑制慢性睡眠剥夺导致的大鼠额叶小胶质细胞活化、减少慢性睡眠剥夺后的炎症因子表达。     

膝骨关节炎患者关节液和滑膜中IL-6、MMP-13、VEGF的表达及与病情进展的关系

目的:研究膝骨关节炎(KOA)患者关节液和滑膜中白细胞介素-6(IL-6)、基质金属蛋白酶-13(MMP-13)、血管内皮生长因子(VEGF)的表达及与病情进展的关系。方法:选择自2017年1月到2017年6月在我院就诊的KOA患者30例进行研究,其中维吾尔族和汉族各15例,分别记为维吾尔族组和汉族组。另选同期在我院接受骨折修复和截肢等手术治疗的10例无骨关节炎的患者作为对照组。对比各组IL-6、MMP-13及VEGF水平以及关节软骨中水通道蛋白3(AQP3)阳性表达率,对比维吾尔族组和汉族组软骨不同区域内AQP3阳性表达,分析KOA患者关节液和滑膜中IL-6、MMP-13、VEGF及关节软骨中AQP3的阳性表达与病情进展的相关性。结果:维吾尔族组和汉族组关节液和滑膜中IL-6、MMP-13及VEGF水平均分别高于对照组,差异均有统计学意义(均P0.05)。维吾尔族组和汉族组关节软骨中AQP3阳性表达率均分别明显高于对照组,且维吾尔族组明显高于汉族组,差异均有统计学意义(均P0.05)。维吾尔族组和汉族组浅层软骨磨损严重区的AQP3阳性表达率明显高于软骨深层区和软骨下骨区,差异均有统计学意义(均P0.05)。Spearman相关性分析显示,KOA患者关节液和滑膜中IL-6、MMP-13、VEGF及关节软骨中AQP3的阳性表达与病情进展均呈正相关(均P0.05)。结论:KOA患者关节液和滑膜中IL-6、MMP-13、VEGF水平及关节软骨中AQP3阳性表达均异常升高,以上指标参与了病情的进展,且AQP3阳性表达高低还与民族有关,临床上可考虑将这些指标作为监测KOA患者病情的靶点。     

Effects of Chronic Sleep Deprivation on the Extracellular Signal-Regulated Kinase Pathway in the Temporomandibular Joint of Rats

Objectives

To examine the possible involvement and regulatory mechanisms of extracellular signal-regulated kinase (ERK) pathway in the temporomandibular joint (TMJ) of rats subjected to chronic sleep deprivation (CSD).

Methods

Rats were subjected to CSD using the modified multiple platform method (MMPM). The serum levels of corticosterone (CORT) and adrenocorticotropic hormone (ACTH) were tested and histomorphology and ultrastructure of the TMJ were observed. The ERK and phospho-ERK (p-ERK) expression levels were detected by Western blot analysis, and the MMP-1, MMP-3, and MMP-13 expression levels were detected by real-time quantitative polymerase chain reaction (PCR) and Western blotting.

Results

The elevated serum CORT and ACTH levels confirmed that the rats were under CSD stress. Hematoxylin and eosin (HE) staining and scanning electron microscopy (SEM) showed pathological alterations in the TMJ following CSD; furthermore, the p-ERK was activated and the mRNA and protein expression levels of MMP-1, MMP-3, and MMP-13 were upregulated after CSD. In the rats administered with the selective ERK inhibitor U0126, decreased tissue destruction was observed. Phospho-ERK activation was visibly blocked and the MMP-1, MMP-3, and MMP-13 mRNA and protein levels were lower than the corresponding levels in the CSD without U0126 group.

Conclusion

These findings indicate that CSD activates the ERK pathway and upregulates the MMP-1, MMP-3, and MMP-13 mRNA and protein levels in the TMJ of rats. Thus, CSD induces ERK pathway activation and causes pathological alterations in the TMJ. ERK may be associated with TMJ destruction by promoting the expression of MMPs.     

莫达非尼对睡眠剥夺条件下工作记忆的影响

目的:观察在睡眠剥夺条件下莫达非尼对工作记忆的改善作用,为此药在我军的应用策略提供实验依据。方法:18名健康男性志愿者,在两次睡眠剥夺实验中交叉服用莫达非尼和安慰剂,睡眠剥夺时间从第一天的07:00到第3d的07:00,并于第二天的0:00、12:00和第三天的0:00分别服用莫达非尼100mg或安慰剂。采用随机双盲设计给药,并在第一天的07:00、第二天的02:00和14:00以及第三天的02:00和07:00安排工作记忆测验。结果:工作记忆测验中,两组的反应时和正确率均有统计学差异(P<0.01),莫达非尼组的反应时要快于安慰剂组,正确率也要高于安慰剂组。莫达非尼对工作记忆的改善效果随着睡眠剥夺时间的延长而更趋明显。结论:莫达非尼对睡眠剥夺条件下个体的工作记忆有改善作用,是较为理想的睡眠剥夺对抗药物。     

The features of sleep homeostasis in pregnant rats

To investigate the effects of short-term sleep deprivation on the sleep pattern during pregnancy, cortical and hippocampal EEG and locomotor activity were recorded within 24-hours in a "disk-over-water" paradigm in 18 Wistar rats. Rats were adapted to experimental situation and were able to move across the rotating disk without falling in water. Then a polysomnogram was recorded for 3 sequential days in the control group 1 (n = 12) without disk rotation. On the next day non-pregnant rats (experimental group 1, n = 6) were subjected to the sleep deprivation procedure with a pre-set program of disk rotation from 11:00 to 14:00 during 3 sequential days. Other 6 rats (experimental group 2) were subjected to sleep deprivation on the 5-7th day of pregnancy. EEG and locomotor activity were also constantly recorded during the sleep deprivation procedure. In control group 2 (n = 6, without sleep deprivation), a polysomnogram was recorded on the 5-7th day of pregnancy. As compared to non-pregnant rats, sleep intensity of pregnant rats increased during the first hours after the deprivation, and a considerable rebound of REM sleep took place. Sleep pattern during the off-light 12 hours remained unchanged. The results suggest that homeostatic compensation of sleep deprivation effects in rats on the first week of pregnancy is more efficient than in control non-pregnant animals.     

咬合运动与注射醋酸泼尼松龙治疗滑膜炎的疗效比较

目的:比较咬合运动和关节下腔注射醋酸泼尼松龙治疗颞下颌关节滑膜炎的临床效果。方法:选择牙列完整、无第三磨牙阻生、符合颞下颌关节滑膜炎诊断标准的120例患者,随机分为实验组和对照组,每组60例。实验组行咬合运动,每次3-4个循环,每日3-4次,治疗周期为12个月;对照组给予醋酸泼尼松龙0.0125g+0.5ml2%利多卡因关节下腔注射一次,比较两种方法的治疗效果。结果:实验组的60例患者均在治疗后1-2w疼痛消失,追踪3-12个月无复发。对照组的60例患者,2个周后有18例无效,无效率为30%,两组比较其结果有显著性差异(P<0.001);3个月后有22例无效,无效率为36.67%,两组比较其结果有显著性差异(P<0.001)。结论:咬合运动组的治疗效果显著高于醋酸泼尼松龙注射组,咬合运动能有效的治疗滑膜炎并减少患者的治疗痛苦。     

抗细胞趋化因子CCL21单克隆抗体处理对小鼠急性心肌梗死后左心室重构及心功能的影响

目的：探讨抗CCL21单克隆抗体处理对小鼠急性心肌梗死后心室重构和心功能的影响。方法：C57BL/6小鼠随机分为假手术组、模型组和CCL21单抗干预组,并进一步分为1、3、7和21 d亚组。采用结扎冠状动脉左前降支的方法构建小鼠急性心肌梗死模型,在冠状动脉结扎后5 min和第3天,模型组小鼠静脉注射isotype-IgG 1.0 mg,CCL21单抗干预组小鼠静脉注射山羊抗小鼠CCL21单克隆抗体1.0 mg。建模后,Western blot法检测急性心肌梗死后第1、3、7天心肌组织CCR7表达,检测急性心肌梗死后第7天心肌组织MMP-2和MMP-9表达;建模后第1、3、7天,ELISA法检测各组小鼠血清TNF-α和IL-6水平,每组检测8只小鼠。在建模后第7天和21天,超声心动图法评估左心室功能变化。结果：与假手术组比较,模型组小鼠急性心肌梗死后血清CCL21、TNF-α和IL-6及心肌组织CCR7、MMP-2、MMP-9明显升高（P<0.05）;与模型组比较,CCL21单抗干预组小鼠血清TNF-α和IL-6及梗死区心肌组织MMP-9水平明显降低（P<0.05）。结论：抗CCL21单克隆抗体处理,通过抑制梗死后炎症反应及MMP-9表达水平发挥防止小鼠心脏重构和保护左心室功能的效应。     

Circadian modification of drug-induced teratogenesis in rat fetuses.

Pregnant Sprague-Dawley rats were injected with hydroxyurea (750 mg/kg) or physiological saline on the 12th day of gestation. Hydroxyurea and saline (control) treated groups were each composed of six subgroups injected at consecutive 4-h intervals (i.e., group 1 at 00(00), group 2 at 04(00),...). All females were injected at the same circadian phase as they were mated. The developmental age of all fetuses was 288 +/- 2 hrs at the time of injection. The fetuses were taken by caesarean section on the 20th or 21st day of gestation. Teratogenesis was greatest when hydroxyurea was administered in the light phase (light-dark 12:12 cycle). Deformity rates correlate with motor activity, mitotic rates and DNA synthesis.     

The Effect of One Night's Sleep Deprivation on Temperature,Mood, and Physical Performance in Subjects with Different Amounts of Habitual Physical Activity

Eleven healthy males were studied twice. On one occasion (control, C), they slept (night 1) and then underwent a battery of tests at 4h intervals from 06: 00 day 1 to 02: 00 day 2; then, after a normal sleep (night 2), they were tested from 10: 00 to 22: 00 on day 2. On the second occasion (sleep deprivation, SD), the subjects remained awake during night 1. Each battery of tests consisted of measurements of tympanic membrane temperature, profile of mood states (POMS), muscle strength, self-chosen work rate (SCWR), perceived exertion, and heart rate (HR) while exercising on a stationary cycle ergometer. Subjects also kept a diary of their activities during the two days and answered a questionnaire about their habitual physical activity. Results showed a significant negative effect of sleep deprivation on most mood states on day 1, but no effect on the other variables. By day 2, mood had tended to recover, though muscle strength tended to be worse in both control and sleep-deprivation experiments. There was also a more general tendency for negative effects to be present at the end of day 1 (02: 00) or at the beginning of day 2 (10: 00). There was limited support for the view that subjects who were habitually more active showed less negative effects after sleep deprivation and responded less adversely to the poor sleep achieved on the university premises (night 2). These results stress the considerable interindividual variation in the responses to sleep loss and, therefore, the difficulty associated with giving general advice to individuals about work or training capability after sleep loss.