基于Integrin/FAK信号通路及颈伸肌群力学性能探讨牵伸松调法治疗颈椎病的作用机制

It is confirmed that cervical spondyloysis is the result of degeneration in “jin” and “bone” as a whole, in which the pathological changes of cervical extensors is the premise and cervical disc is the foundation, and CEP is the initial factor of degeneration in disc as well as cervical vertebral body. With the verification of previous study, the manipulation of Extension-Tenolysis-Adjustment(ETA) manipulation can adjust the relative factors expressing in the model rabbits of cervical spondyloysis and is more effective , timesaving and laboursaving in the clinic. Hence, this study take “emphasize jin consider bone” as principle, and “loosen jin adjust bone” as method, put forward the effective binary channels scientific hypothesis of “ETA intervention-- improvement of ultra microstructure and mechanical property of the cervical extensors--enhancement of abilities of exogenous equilibrium” and “ETA intervention--improvement of micro-structure of CEP, cervical abnormal curvature and abnormal state of the accessory structure--strengthening of abilities of endogenous equilibrium”, observing the change of microstructure and gene expression of p-FAK,NF-κB,MyoD of CEP and cervical extensors in experimental animals as well as sEMG,PainVision,scales of NPQ and SF-36 applied in the clinic before and after the ETA intervene, aims to explore the mechanism of ETA on cervical spondylosis based on the signal channel of Integrin/FAK and mechanical property of cervical extensors, to evaluate the clinic value in multiple angles and levels, to provide scientific evidence of Tuina for cervical spondylosis.

颈椎病是“筋-骨”一体退变的结果，颈伸肌群的病变是退变的前提，椎间盘的退变是基础，软骨终板（CEP）的退变则是椎间盘乃至颈椎退变的起始因素。前期的研究证实，牵伸松调法能调节颈椎病模型兔相关因子的表达，临床应用省时省力，疗效显著。因此，本课题以“重筋顾骨”为治则，“松筋调骨”为治法，提出“手法干预-颈伸肌群超微结构及力学性能改善-外源性平衡能力增强”及“手法干预-CEP超微结构、颈曲及附属关节状态改善-内源性平衡能力提高”双通道起作用的科学假说。拟通过电镜观察实验动物手法干预前后CEP与颈伸肌群肌超微结构变化及p-FAK、NF-κB、MyoD等相关基因的表达，并借助sEMG、PainVision等设备及NPQ、SF-36等量表，从Integrin/FAK信号通路及颈伸肌群力学性能的层面探讨手法治疗颈椎病的机理，多角度、多层次的评估手法治疗颈椎病的临床价值，为推拿治疗颈椎病提供客观科学的依据。

颈椎病是临床常见病与多发病，推拿手法治疗有较好疗效，但深层的作用机制仍不清楚。研究发现，颈椎病是“筋-骨”一体退变的结果，颈肌病变是颈椎退变的前提，椎间盘的退变是核心环节，软骨终板（CEP）的退变则是椎间盘乃至颈椎退变的起始因素。本课题以“重筋顾骨”为治则，“松筋调骨”为治法，提出“手法干预-颈伸肌群超微结构及力学性能改善-外源性平衡能力增强”及“手法干预-CEP超微结构、颈曲及附属关节状态改善-内源性平衡能力提高”双通道起作用的科学假说。通过电镜观察实验动物手法干预前后颈肌超微结构变化及p-FAK、NF-κB、MyoD等相关基因的表达，借助sEMG、PainVision等设备及NPQ、SF-36等量表，从Integrin/FAK信号通路及颈伸肌群力学性能的层面探讨手法治疗颈椎病的机理。动物实验研究证实，牵伸松调法一方面可以改善颈伸肌纤维Z 线、肌丝及肌纤维的排列，减轻肌节肿胀胀及肌浆网的扩张，下调颈肌组织炎性因子IL-6、IL-1β、NF-κB与成肌调节因子MyoD的表达水平，并抑制凋亡蛋白Caspase-1、Caspase-3及Caspase-8的表达，对颈肌软组织的修复有促进作用；另一方面，牵伸松调法还可下调CEP关节软骨炎性因子IL-6、IL-1β及凋亡蛋白Caspase-1、Caspase-3及Caspase-8的表达水平，上调CEP关节软骨p-FAK、p-P13K、p-AKT的表达，证实手法的力学信号干预可促进CEP基质细胞主要物质Col-Ⅱ、Aggrecan的合成，为保护软骨细胞，促进软骨的修复创造了重要条件，从Integrin/FAK信号通路及颈伸肌群力学性能的角度诠释了手法治疗颈椎病有效的分子机制。临床研究表明，牵伸松调法可显著降低颈椎病患者颈痛与躯体疼痛，有效缓解伴随的焦虑与抑郁状态，提高情感职能和精神健康等生活质量指标(SF-36)，增强颈肌抗疲劳能力及力学性能，且远期疗效稳定，值得推广。