黨保平 閆金洪 韓一生

膝交叉韌帶中機(jī)械感受器的研究進(jìn)展

黨保平 閆金洪 韓一生

前交叉韌帶；后交叉韌帶；機(jī)械感受器；骨關(guān)節(jié)炎，膝；本體感覺(jué)

膝關(guān)節(jié)交叉韌帶是維持膝關(guān)節(jié)穩(wěn)定的重要結(jié)構(gòu)，具有兩種重要功能：生物力學(xué)功能和本體感覺(jué)功能。生物力學(xué)功能主要是指交叉韌帶防止膝關(guān)節(jié)在運(yùn)動(dòng)過(guò)程中脛骨過(guò)度向前或向后移位。本體感覺(jué)功能是指膝關(guān)節(jié)對(duì)空間運(yùn)動(dòng)和位置感知的一種能力，主要通過(guò)位于韌帶、關(guān)節(jié)囊，肌肉和皮膚等處的機(jī)械感受器來(lái)感知[1]。日常生活中，年輕人多發(fā)生交叉韌帶特別是前交叉韌帶[2]的急性損傷或斷裂，老年人多發(fā)生交叉韌帶形態(tài)及功能的退變[3-5]。交叉韌帶的損傷與退變可能會(huì)導(dǎo)致機(jī)械感受器形態(tài)及數(shù)量的變化，同時(shí)帶來(lái)膝關(guān)節(jié)本體感覺(jué)的變化。筆者圍繞近年來(lái)交叉韌帶損傷與退變中機(jī)械感受器的研究進(jìn)展進(jìn)行綜述，并探索機(jī)械感受器的變化規(guī)律及其與本體感覺(jué)的關(guān)系。

一、膝關(guān)節(jié)交叉韌帶的組織解剖

膝關(guān)節(jié)交叉韌帶分為前交叉韌帶 ( anterior cruciate ligament，ACL )、后交叉韌帶 ( posterior cruciate ligament，PCL ) 兩條，兩者位于脛骨髁間隆起及股骨髁間窩之間，呈鉸鏈?zhǔn)剑址Q(chēng)十字韌帶。其中 ACL 起于股骨外髁內(nèi)后側(cè)面，向下、向前、向內(nèi)止于脛骨髁間隆起的前方，PCL起于股骨內(nèi)側(cè)髁的外側(cè)面，向后、向下止于脛骨髁間隆起的后方。朱偉[6]對(duì) ACL 和 PCL 的構(gòu)成及功能闡述如下：ACL 由前內(nèi)側(cè)束 ( AM ) 和后外側(cè)束 ( PL ) 兩個(gè)功能束組成，兩者緊張模式相反，前內(nèi)側(cè)束于屈膝時(shí)產(chǎn)生最大張力，后外側(cè)束于伸膝產(chǎn)生最大張力。這兩束可限制脛骨向前過(guò)度移位，同時(shí)后外側(cè)束在伸膝狀態(tài)下產(chǎn)生的最大張力使其在膝關(guān)節(jié)旋轉(zhuǎn)穩(wěn)定中也起著重要作用。前交叉韌帶獨(dú)特的解剖結(jié)構(gòu)，使得它在膝關(guān)節(jié)做外翻、內(nèi)翻動(dòng)作時(shí)容易斷裂。PCL 由前外側(cè)束 ( AL ) 和后內(nèi)側(cè)束 ( PM ) 兩束構(gòu)成，前外側(cè)束在膝關(guān)節(jié)屈曲 90° 時(shí)產(chǎn)生最大張力，后內(nèi)側(cè)束在膝關(guān)節(jié)伸直和最大屈曲時(shí)產(chǎn)生最大張力。這兩束具有防止脛骨過(guò)度向后移位作用外，還可限制膝關(guān)節(jié)的過(guò)伸、過(guò)屈及旋轉(zhuǎn)活動(dòng)。膝關(guān)節(jié)的穩(wěn)定除需要前、后交叉韌帶外，還要聯(lián)合膝關(guān)節(jié)內(nèi)其它組織共同來(lái)維持，從而使人體完成各種復(fù)雜和高難度的下肢動(dòng)作。

二、膝關(guān)節(jié)交叉韌帶機(jī)械感受器

1.交叉韌帶機(jī)械感受器的分類(lèi)及功能：自從發(fā)現(xiàn)人類(lèi)交叉韌帶中存在機(jī)械感受器后[7-8]，學(xué)者們就一直在對(duì)其進(jìn)行研究，但由于關(guān)注點(diǎn)不同，不同的學(xué)者對(duì)其描述差異性較大，其具體分類(lèi)也就沒(méi)有統(tǒng)一的意見(jiàn)。在總結(jié)前人經(jīng)驗(yàn)的基礎(chǔ)上，F(xiàn)reeman 等[9]提出了目前被大家認(rèn)同的較為合理的分類(lèi)：I 類(lèi)為 Ruffini 末梢即魯菲尼氏末梢，II 類(lèi)為Pacinian 小體即帕西尼小體，III 類(lèi)為 Golgi 腱器末梢即高爾基腱器末梢，IV 類(lèi)為游離神經(jīng)末梢 ( free nerve endigs )。

膝關(guān)節(jié)四種機(jī)械感受器的功能主要是感知膝關(guān)節(jié)張力、速度、加速度、移動(dòng)方向以及膝關(guān)節(jié)位置[10-11]，但是每種機(jī)械感受器又有其各自的形態(tài)和功能。魯菲尼氏末梢是一種觸覺(jué)感受器，主要表現(xiàn)為呈卵圓形或疏松樹(shù)突狀神經(jīng)纖維末梢，它的被膜相對(duì)比較松弛且薄，是一種慢適應(yīng)、低閾值感受器，主要感知膝關(guān)節(jié)運(yùn)動(dòng)時(shí)的角度、速度、關(guān)節(jié)腔內(nèi)壓力以及關(guān)節(jié)靜止時(shí)位置[12]。帕西尼氏小體是一種橢圓形或圓形的壓力感受器，由多層膠原纖維包繞一個(gè)長(zhǎng)的中心部構(gòu)成，各層之間有一薄層間隙，它與魯菲尼氏末梢慢適應(yīng)特點(diǎn)相反，是一種快適應(yīng)、低閾值感受器，其主要作用是產(chǎn)生關(guān)節(jié)運(yùn)動(dòng)覺(jué)，對(duì)關(guān)節(jié)位置的改變非常敏感[13]。高爾基腱器末梢呈梭形，與其它三種感受器相比形態(tài)最大，是一種運(yùn)動(dòng)感受器，它的被膜相對(duì)較薄，與魯菲尼氏末梢低閾值特點(diǎn)相反，是一種高閾值、慢適應(yīng)感受器，在關(guān)節(jié)活動(dòng)、肌肉主動(dòng)收縮時(shí)，它的沖動(dòng)發(fā)放頻率明顯增加。游離神經(jīng)末梢是無(wú)髓鞘神經(jīng)纖維終末部分失去施萬(wàn)細(xì)胞裸露的軸突末端細(xì)支，在韌帶中數(shù)量相對(duì)比較多，它的長(zhǎng)軸方向與韌帶方向平行，主要感受關(guān)節(jié)炎和疼痛刺激[12]，并且可能具有血管舒縮功能[8]。每種感受器根據(jù)各自特點(diǎn)接受適宜刺激，并把這種刺激傳遞到中樞神經(jīng)系統(tǒng)，中樞神經(jīng)系統(tǒng)及時(shí)作出反應(yīng)，調(diào)節(jié)身體的平衡。

2.交叉韌帶機(jī)械感受器的空間分布：Franchi 等[14]通過(guò)對(duì)正常膝關(guān)節(jié)和患有骨關(guān)節(jié)炎患者的 PCL 研究發(fā)現(xiàn)機(jī)械感受器占據(jù)整條韌帶組織的 1%，且魯菲尼氏末梢、帕西尼小體、高爾基腱器末梢主要附著于脛骨附麗點(diǎn)，而游離神經(jīng)末梢主要附著于股骨附麗點(diǎn)。Raunest、Halata 等通過(guò)研究羊交叉韌帶發(fā)現(xiàn)，機(jī)械感受器主要分布于脛骨和股骨附麗點(diǎn)[15-16]。更多的學(xué)者通過(guò)研究人交叉韌帶認(rèn)為機(jī)械感受器主要分布在韌帶脛骨和股骨附麗處，占韌帶組織的1%～2.5%[17-18]。筆者在臨床上發(fā)現(xiàn)交叉韌帶損傷位置更多的發(fā)生于體部，明顯高于韌帶在股骨附麗點(diǎn)和脛骨附麗點(diǎn)，而機(jī)械感受器又主要集中于脛骨和股骨附麗點(diǎn)，交叉韌帶的這種損傷特點(diǎn)和機(jī)械感受器的分布位置有無(wú)關(guān)聯(lián)，目前不得而知。

3.交叉韌帶機(jī)械感受器與本體感覺(jué)：交叉韌帶機(jī)械感受器作為本體感覺(jué)形成的關(guān)鍵，通過(guò)與膝關(guān)節(jié)三維空間結(jié)構(gòu)的相互作用，把膝關(guān)節(jié)在空間所處位置及運(yùn)動(dòng)狀態(tài)信息傳向中樞神經(jīng)系統(tǒng)，中樞神經(jīng)系統(tǒng)通過(guò)對(duì)機(jī)械感受器所傳遞信息的整合形成膝關(guān)節(jié)在空間的位置覺(jué)和運(yùn)動(dòng)覺(jué)，同時(shí)為了控制軀體的平衡，中樞神經(jīng)系統(tǒng)還要整合本體感覺(jué)、軀體感覺(jué)、視覺(jué)和前庭信息，反饋調(diào)節(jié)相應(yīng)的骨骼肌肉做出姿勢(shì)反應(yīng)[18-23]。

膝關(guān)節(jié)本體感覺(jué)會(huì)隨著年齡增長(zhǎng)而輕微減弱，但是當(dāng)本體感覺(jué)突然減弱時(shí)，則可能是由一些突發(fā)原因引起的，如交叉韌帶的切除或急性損傷等[24]。交叉韌帶機(jī)械感受器作為本體感覺(jué)的感受器官，其數(shù)量變化會(huì)帶來(lái)本體感覺(jué)的變化，有研究發(fā)現(xiàn) ACL 機(jī)械感受器數(shù)量與膝關(guān)節(jié)本體感覺(jué)呈正相關(guān)[25]，膝交叉韌帶受損后時(shí)間越短，脛骨、股骨兩端殘留的韌帶越長(zhǎng)，膝關(guān)節(jié)本體感覺(jué)越好[26]。此外，有研究報(bào)道全膝關(guān)節(jié)置換術(shù)中完全切除含有機(jī)械感受器的交叉韌帶，術(shù)后患者膝關(guān)節(jié)本體感覺(jué)比單髁關(guān)節(jié)置換術(shù)后患者 ( 未切除交叉韌帶 ) 或保留 PCL 的全膝關(guān)節(jié)置換術(shù)后患者本體感覺(jué)差[18,21,27-28]，交叉韌帶的切除，必然使機(jī)械感受器數(shù)量減少，本體感覺(jué)也就會(huì)隨之降低。

三、交叉韌帶損傷與機(jī)械感受器

交叉韌帶急性損傷后，膠原纖維結(jié)構(gòu)破壞會(huì)導(dǎo)致韌帶松弛，引起機(jī)械感受器反應(yīng)閾值的提高；此外，韌帶的神經(jīng)傳入功能 ( 機(jī)械感受器數(shù)量的減少或變性造成的 ) 也可能受損[1]，從而使膝關(guān)節(jié)本體感覺(jué)信息形成的始發(fā)階段受到影響，引起膝關(guān)節(jié)本體感覺(jué)減弱[29-31]。針對(duì)交叉韌帶損傷后機(jī)械感受器的變化情況，有學(xué)者研究發(fā)現(xiàn)機(jī)械感受器數(shù)量會(huì)隨著韌帶受損時(shí)間的延長(zhǎng)而發(fā)生變化，受損時(shí)間越長(zhǎng)，機(jī)械感受器數(shù)量越少[10,32]。有學(xué)者研究發(fā)現(xiàn)交叉韌帶中機(jī)械感受器在損傷后 12 個(gè)月內(nèi)并沒(méi)有發(fā)生明顯的萎縮與減少[33]。上述兩種不同結(jié)果，可能是由于研究者研究方法的不同、觀察時(shí)間長(zhǎng)短不同以及取材標(biāo)準(zhǔn)不同等造成。

在研究交叉韌帶損傷后機(jī)械感受器變化情況的基礎(chǔ)上，有學(xué)者對(duì)修復(fù)重建交叉韌帶后機(jī)械感受器及本體感覺(jué)變化情況進(jìn)行了研究，他們發(fā)現(xiàn)交叉韌帶在移植修復(fù)后本體感覺(jué)會(huì)恢復(fù)，但不能達(dá)到正常水平，并且需要較長(zhǎng)時(shí)間[34-35]，這可能主要是因?yàn)閷?duì)交叉韌帶移植修復(fù)后，通過(guò)完好無(wú)損或殘余韌帶上的血管及機(jī)械感受器可以促進(jìn)血管的再生和神經(jīng)再支配，從而使膝關(guān)節(jié)本體感覺(jué)再恢復(fù)，同時(shí)也提供了生物力學(xué)的穩(wěn)定[36-37]，而且有學(xué)者通過(guò)對(duì)動(dòng)物及人修復(fù)重建后的韌帶進(jìn)行研究發(fā)現(xiàn)有機(jī)械感受器再生[38-39]，當(dāng)然上述感受器的再生是在自體韌帶修復(fù)重建的基礎(chǔ)上，有學(xué)者通過(guò)對(duì)異體移植物修復(fù)重建交叉韌帶研究后并未發(fā)現(xiàn)機(jī)械感受器的再生[40]。

四、交叉韌帶退變與機(jī)械感受器

骨關(guān)節(jié)炎 ( osteoarthrosis，OA ) 是指由于關(guān)節(jié)軟骨變性、骨質(zhì)增生而引起的一種慢性骨關(guān)節(jié)疾患，其發(fā)病原因較多，年齡和創(chuàng)傷是其兩個(gè)主要危險(xiǎn)因素[41]，此外，交叉韌帶損傷所引起的關(guān)節(jié)不穩(wěn)及關(guān)節(jié)軟骨的破壞也是引起骨關(guān)節(jié)炎的原因之一[42-45]。在骨關(guān)節(jié)炎病情發(fā)展過(guò)程中交叉韌帶會(huì)逐漸發(fā)生退變，功能也隨之降低[46-49]，膝關(guān)節(jié)本體感覺(jué)也會(huì)慢慢減弱[50-51]，可使患者有跌倒風(fēng)險(xiǎn)的存在。交叉韌帶退變過(guò)程主要是與炎癥相關(guān)聯(lián)，是一種主動(dòng)地、細(xì)胞介導(dǎo)的細(xì)胞外基質(zhì)減少和重塑的過(guò)程[52]，而韌帶的退變及膝關(guān)節(jié)本體感覺(jué)的減弱又促進(jìn)骨關(guān)節(jié)炎的進(jìn)一步發(fā)展[19,53-54]，兩者是相互促進(jìn)的存在。

骨關(guān)節(jié)炎患者退變交叉韌帶由于還存在血液供應(yīng)，機(jī)械感受器數(shù)量變化情況及其與骨關(guān)節(jié)炎病程、病情嚴(yán)重程度的關(guān)聯(lián)情況還不清楚。如果機(jī)械感受器會(huì)隨著骨關(guān)節(jié)炎病情的發(fā)展、交叉韌帶的退變而發(fā)生數(shù)量的減少和功能的減弱，那么就可在患者就診早期指導(dǎo)其進(jìn)行膝關(guān)節(jié)本體感覺(jué)功能及肌力的鍛煉，使機(jī)械感受器數(shù)量、功能得以保存，減少膝關(guān)節(jié)本體感覺(jué)的喪失，從一定程度上延緩骨關(guān)節(jié)炎病情的發(fā)展及交叉韌帶的退變，降低患者跌倒的風(fēng)險(xiǎn)。此外有研究報(bào)道骨關(guān)節(jié)炎患者全膝關(guān)節(jié)置換術(shù)前跌倒的風(fēng)險(xiǎn)與術(shù)后跌倒風(fēng)險(xiǎn)相關(guān)[55]，術(shù)前膝關(guān)節(jié)本體感覺(jué)功能及肌力的鍛煉也有助于改進(jìn)術(shù)后關(guān)節(jié)平衡能力、步態(tài)、步速以及主觀功能評(píng)分[48]，降低患者膝關(guān)節(jié)置換術(shù)后跌倒的風(fēng)險(xiǎn)，改善患者的生活質(zhì)量。

五、展望

受損膝交叉韌帶在移植修復(fù)后機(jī)械感受器數(shù)量及本體感覺(jué)會(huì)恢復(fù)一部分，但并不能完全恢復(fù)到損傷前狀態(tài)，患者仍有再損傷及跌倒的風(fēng)險(xiǎn)，甚至發(fā)生骨關(guān)節(jié)炎[56-57]。針對(duì)這一臨床問(wèn)題，目前只能指導(dǎo)患者進(jìn)行肌力鍛煉，同時(shí)聯(lián)合髖關(guān)節(jié)及踝關(guān)節(jié)的共同協(xié)調(diào)來(lái)保持膝關(guān)節(jié)的穩(wěn)定。未來(lái)研究可能要進(jìn)一步加強(qiáng)組織工程韌帶的研究，使在體外分離培養(yǎng)的韌帶細(xì)胞培養(yǎng)成組織工程韌帶，更加接近于人體正常韌帶結(jié)構(gòu)，以便交叉韌帶在移植修復(fù)后，通過(guò)更好的血管再生及神經(jīng)再分布促進(jìn)膝關(guān)節(jié)本體感覺(jué)的恢復(fù)。

骨關(guān)節(jié)炎患者交叉韌帶退變的同時(shí)會(huì)出現(xiàn)膝關(guān)節(jié)本體感覺(jué)減弱，但交叉韌帶中機(jī)械感受器是否隨著韌帶的退變而發(fā)生數(shù)量的減少和形態(tài)的破壞，目前并不清楚，這就需要更多的研究集中于交叉韌帶機(jī)械感受器，探索其在骨關(guān)節(jié)炎中變化規(guī)律，從而為骨關(guān)節(jié)炎患者的病情的預(yù)防及治療帶來(lái)更加科學(xué)的方案。

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( 本文編輯：裴艷宏 李貴存 )

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，第四軍醫(yī)大學(xué)西京醫(yī)院骨科

韓一生，Email: drhanys@fmmu.edu.cn

2016-09-08 )