膝交叉韧带中机械感受器的研究进展

党保平 闫金洪 韩一生

膝交叉韧带中机械感受器的研究进展

党保平 闫金洪 韩一生

前交叉韧带；后交叉韧带；机械感受器；骨关节炎，膝；本体感觉

膝关节交叉韧带是维持膝关节稳定的重要结构，具有两种重要功能：生物力学功能和本体感觉功能。生物力学功能主要是指交叉韧带防止膝关节在运动过程中胫骨过度向前或向后移位。本体感觉功能是指膝关节对空间运动和位置感知的一种能力，主要通过位于韧带、关节囊，肌肉和皮肤等处的机械感受器来感知[1]。日常生活中，年轻人多发生交叉韧带特别是前交叉韧带[2]的急性损伤或断裂，老年人多发生交叉韧带形态及功能的退变[3-5]。交叉韧带的损伤与退变可能会导致机械感受器形态及数量的变化，同时带来膝关节本体感觉的变化。笔者围绕近年来交叉韧带损伤与退变中机械感受器的研究进展进行综述，并探索机械感受器的变化规律及其与本体感觉的关系。

一、膝关节交叉韧带的组织解剖

膝关节交叉韧带分为前交叉韧带 ( anterior cruciate ligament，ACL )、后交叉韧带 ( posterior cruciate ligament，PCL ) 两条，两者位于胫骨髁间隆起及股骨髁间窝之间，呈铰链式，又称十字韧带。其中 ACL 起于股骨外髁内后侧面，向下、向前、向内止于胫骨髁间隆起的前方，PCL起于股骨内侧髁的外侧面，向后、向下止于胫骨髁间隆起的后方。朱伟[6]对 ACL 和 PCL 的构成及功能阐述如下：ACL 由前内侧束 ( AM ) 和后外侧束 ( PL ) 两个功能束组成，两者紧张模式相反，前内侧束于屈膝时产生最大张力，后外侧束于伸膝产生最大张力。这两束可限制胫骨向前过度移位，同时后外侧束在伸膝状态下产生的最大张力使其在膝关节旋转稳定中也起着重要作用。前交叉韧带独特的解剖结构，使得它在膝关节做外翻、内翻动作时容易断裂。PCL 由前外侧束 ( AL ) 和后内侧束 ( PM ) 两束构成，前外侧束在膝关节屈曲 90° 时产生最大张力，后内侧束在膝关节伸直和最大屈曲时产生最大张力。这两束具有防止胫骨过度向后移位作用外，还可限制膝关节的过伸、过屈及旋转活动。膝关节的稳定除需要前、后交叉韧带外，还要联合膝关节内其它组织共同来维持，从而使人体完成各种复杂和高难度的下肢动作。

二、膝关节交叉韧带机械感受器

1.交叉韧带机械感受器的分类及功能：自从发现人类交叉韧带中存在机械感受器后[7-8]，学者们就一直在对其进行研究，但由于关注点不同，不同的学者对其描述差异性较大，其具体分类也就没有统一的意见。在总结前人经验的基础上，Freeman 等[9]提出了目前被大家认同的较为合理的分类：I 类为 Ruffini 末梢即鲁菲尼氏末梢，II 类为Pacinian 小体即帕西尼小体，III 类为 Golgi 腱器末梢即高尔基腱器末梢，IV 类为游离神经末梢 ( free nerve endigs )。

膝关节四种机械感受器的功能主要是感知膝关节张力、速度、加速度、移动方向以及膝关节位置[10-11]，但是每种机械感受器又有其各自的形态和功能。鲁菲尼氏末梢是一种触觉感受器，主要表现为呈卵圆形或疏松树突状神经纤维末梢，它的被膜相对比较松弛且薄，是一种慢适应、低阈值感受器，主要感知膝关节运动时的角度、速度、关节腔内压力以及关节静止时位置[12]。帕西尼氏小体是一种椭圆形或圆形的压力感受器，由多层胶原纤维包绕一个长的中心部构成，各层之间有一薄层间隙，它与鲁菲尼氏末梢慢适应特点相反，是一种快适应、低阈值感受器，其主要作用是产生关节运动觉，对关节位置的改变非常敏感[13]。高尔基腱器末梢呈梭形，与其它三种感受器相比形态最大，是一种运动感受器，它的被膜相对较薄，与鲁菲尼氏末梢低阈值特点相反，是一种高阈值、慢适应感受器，在关节活动、肌肉主动收缩时，它的冲动发放频率明显增加。游离神经末梢是无髓鞘神经纤维终末部分失去施万细胞裸露的轴突末端细支，在韧带中数量相对比较多，它的长轴方向与韧带方向平行，主要感受关节炎和疼痛刺激[12]，并且可能具有血管舒缩功能[8]。每种感受器根据各自特点接受适宜刺激，并把这种刺激传递到中枢神经系统，中枢神经系统及时作出反应，调节身体的平衡。

2.交叉韧带机械感受器的空间分布：Franchi 等[14]通过对正常膝关节和患有骨关节炎患者的 PCL 研究发现机械感受器占据整条韧带组织的 1%，且鲁菲尼氏末梢、帕西尼小体、高尔基腱器末梢主要附着于胫骨附丽点，而游离神经末梢主要附着于股骨附丽点。Raunest、Halata 等通过研究羊交叉韧带发现，机械感受器主要分布于胫骨和股骨附丽点[15-16]。更多的学者通过研究人交叉韧带认为机械感受器主要分布在韧带胫骨和股骨附丽处，占韧带组织的1%～2.5%[17-18]。笔者在临床上发现交叉韧带损伤位置更多的发生于体部，明显高于韧带在股骨附丽点和胫骨附丽点，而机械感受器又主要集中于胫骨和股骨附丽点，交叉韧带的这种损伤特点和机械感受器的分布位置有无关联，目前不得而知。

3.交叉韧带机械感受器与本体感觉：交叉韧带机械感受器作为本体感觉形成的关键，通过与膝关节三维空间结构的相互作用，把膝关节在空间所处位置及运动状态信息传向中枢神经系统，中枢神经系统通过对机械感受器所传递信息的整合形成膝关节在空间的位置觉和运动觉，同时为了控制躯体的平衡，中枢神经系统还要整合本体感觉、躯体感觉、视觉和前庭信息，反馈调节相应的骨骼肌肉做出姿势反应[18-23]。

膝关节本体感觉会随着年龄增长而轻微减弱，但是当本体感觉突然减弱时，则可能是由一些突发原因引起的，如交叉韧带的切除或急性损伤等[24]。交叉韧带机械感受器作为本体感觉的感受器官，其数量变化会带来本体感觉的变化，有研究发现 ACL 机械感受器数量与膝关节本体感觉呈正相关[25]，膝交叉韧带受损后时间越短，胫骨、股骨两端残留的韧带越长，膝关节本体感觉越好[26]。此外，有研究报道全膝关节置换术中完全切除含有机械感受器的交叉韧带，术后患者膝关节本体感觉比单髁关节置换术后患者 ( 未切除交叉韧带 ) 或保留 PCL 的全膝关节置换术后患者本体感觉差[18,21,27-28]，交叉韧带的切除，必然使机械感受器数量减少，本体感觉也就会随之降低。

三、交叉韧带损伤与机械感受器

交叉韧带急性损伤后，胶原纤维结构破坏会导致韧带松弛，引起机械感受器反应阈值的提高；此外，韧带的神经传入功能 ( 机械感受器数量的减少或变性造成的 ) 也可能受损[1]，从而使膝关节本体感觉信息形成的始发阶段受到影响，引起膝关节本体感觉减弱[29-31]。针对交叉韧带损伤后机械感受器的变化情况，有学者研究发现机械感受器数量会随着韧带受损时间的延长而发生变化，受损时间越长，机械感受器数量越少[10,32]。有学者研究发现交叉韧带中机械感受器在损伤后 12 个月内并没有发生明显的萎缩与减少[33]。上述两种不同结果，可能是由于研究者研究方法的不同、观察时间长短不同以及取材标准不同等造成。

在研究交叉韧带损伤后机械感受器变化情况的基础上，有学者对修复重建交叉韧带后机械感受器及本体感觉变化情况进行了研究，他们发现交叉韧带在移植修复后本体感觉会恢复，但不能达到正常水平，并且需要较长时间[34-35]，这可能主要是因为对交叉韧带移植修复后，通过完好无损或残余韧带上的血管及机械感受器可以促进血管的再生和神经再支配，从而使膝关节本体感觉再恢复，同时也提供了生物力学的稳定[36-37]，而且有学者通过对动物及人修复重建后的韧带进行研究发现有机械感受器再生[38-39]，当然上述感受器的再生是在自体韧带修复重建的基础上，有学者通过对异体移植物修复重建交叉韧带研究后并未发现机械感受器的再生[40]。

四、交叉韧带退变与机械感受器

骨关节炎 ( osteoarthrosis，OA ) 是指由于关节软骨变性、骨质增生而引起的一种慢性骨关节疾患，其发病原因较多，年龄和创伤是其两个主要危险因素[41]，此外，交叉韧带损伤所引起的关节不稳及关节软骨的破坏也是引起骨关节炎的原因之一[42-45]。在骨关节炎病情发展过程中交叉韧带会逐渐发生退变，功能也随之降低[46-49]，膝关节本体感觉也会慢慢减弱[50-51]，可使患者有跌倒风险的存在。交叉韧带退变过程主要是与炎症相关联，是一种主动地、细胞介导的细胞外基质减少和重塑的过程[52]，而韧带的退变及膝关节本体感觉的减弱又促进骨关节炎的进一步发展[19,53-54]，两者是相互促进的存在。

骨关节炎患者退变交叉韧带由于还存在血液供应，机械感受器数量变化情况及其与骨关节炎病程、病情严重程度的关联情况还不清楚。如果机械感受器会随着骨关节炎病情的发展、交叉韧带的退变而发生数量的减少和功能的减弱，那么就可在患者就诊早期指导其进行膝关节本体感觉功能及肌力的锻炼，使机械感受器数量、功能得以保存，减少膝关节本体感觉的丧失，从一定程度上延缓骨关节炎病情的发展及交叉韧带的退变，降低患者跌倒的风险。此外有研究报道骨关节炎患者全膝关节置换术前跌倒的风险与术后跌倒风险相关[55]，术前膝关节本体感觉功能及肌力的锻炼也有助于改进术后关节平衡能力、步态、步速以及主观功能评分[48]，降低患者膝关节置换术后跌倒的风险，改善患者的生活质量。

五、展望

受损膝交叉韧带在移植修复后机械感受器数量及本体感觉会恢复一部分，但并不能完全恢复到损伤前状态，患者仍有再损伤及跌倒的风险，甚至发生骨关节炎[56-57]。针对这一临床问题，目前只能指导患者进行肌力锻炼，同时联合髋关节及踝关节的共同协调来保持膝关节的稳定。未来研究可能要进一步加强组织工程韧带的研究，使在体外分离培养的韧带细胞培养成组织工程韧带，更加接近于人体正常韧带结构，以便交叉韧带在移植修复后，通过更好的血管再生及神经再分布促进膝关节本体感觉的恢复。

骨关节炎患者交叉韧带退变的同时会出现膝关节本体感觉减弱，但交叉韧带中机械感受器是否随着韧带的退变而发生数量的减少和形态的破坏，目前并不清楚，这就需要更多的研究集中于交叉韧带机械感受器，探索其在骨关节炎中变化规律，从而为骨关节炎患者的病情的预防及治疗带来更加科学的方案。

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( 本文编辑：裴艳宏 李贵存 )

Progress in studies on the mechanoreceptors in the cruciate ligament

DANG Bao-ping, YAN Jin-hong, HAN Yi-sheng.
Department of Orthopaedics, Xijing Hospital, the fourth Military Medical University, X’ian, Shanxi, 710032, PRC
Coponding author: HAN Yi-sheng, Email: drhanys@fmmu.edu.cn

Cruciate ligament of the knee lies between tibia intercondylar eminence and femoral condyle nest, presents hinged appearance and has both the function of biomechanics and proprioception, which is processed using mechanoreceptors in the tibial and femoral ligament attachment point.Mechanoreceptors could be divided into 4 groups: Ruffini ending, Pacinian body, Golgi tendon ending, and free nerve ending.The amount of mechanoreceptors of the cruciate ligament after acute injury will change in line with the duration of injury: the longer the time lasts, the less the receptors will be.But some hold the opposite view and consider that the receptors do not have evident atrophy and decline.Due to inflammation in the progression of osteoarthritis, cruciate ligament will gradually degenerate, and knee proprioception will abate as well.However, whether the amount of mechanoreceptors are associated with osteoarthritis progression and severity of the situation is not clear.The number of the damaged cruciate ligament mechanoreceptors and proprioception can recover partly after transplantation and repair, but not fully recover.Therefore, whether separated and cultured cells in vitro can be used in tissue engineering for ligament transplantation and repair, and improve proprioception, is what we need to pay attention to in the future, in order to provide more therapeutic measures for the clinic.

Anterior cruciate ligament; Posterior cruciate ligament; Mechanoreceptors; Osteoarthritis, knee; Proprioception

10.3969/j.issn.2095-252X.2016.12.011

R684.3

710032 西安，第四军医大学西京医院骨科

韩一生，Email: drhanys@fmmu.edu.cn

2016-09-08 )