SDF-1/CXCR4介导的PI3K/AKt/mTOR信号通路在电针干预椎动脉型颈椎病中的调控机制

Cervical spondylotic arteriopathy (CSA) is more prevalent in younger populations, and its etiology is believed to be closely associated with vertebral artery insufficiency. Acupuncture is a common treatment approach for CSA. Current research mainly focuses on macroscopic morphology and flow velocity of the vertebral artery. Previous studies have found that electroacupuncture can stimulate the expression of stromal cell-derived factor-1/chemokine receptor type 4(SDF-1/CXCR4), a key signaling molecule that can increase vascular proliferation. Moreover, electroacupuncture can achieve revascularization ininjured tissues by activating phosphatidylinositol 3-kinase(PI3K) and protein kinase B (also known as Akt). However, it is still not clear whether electroacupuncture can exert a therapeutic effect on CSA through an SDF-1/CXCR4-mediated PI3K/Akt signaling pathway. In this study, a rabbit CSA model was established. The effects of electroacupuncture intervention on the hemodynamics and micro-morphology of the vertebral artery in the CSA rabbits were then observed macroscopically and microscopically. In addition, the underlying mechanisms of the SDF-1/CXCR4-mediated PI3K/Akt/mTOR signaling pathway in the pathogenesis of CSA and the potential regulatory pathways that electroacupuncture actions were investigated by Western blot, reverse transcription-polymerase chain reaction (RT-PCR) and methylation-specific PCR. Our study demonstrates the action mechanism of electroacupuncture on CSA rabbits using an in-depth and novel approach, and our findings may help to promote a wider application of acupuncture in patients with cervical spondylopathy.

椎动脉型颈椎病（CSA）呈明显年轻化趋势，多认为与椎动脉供血不足密切相关。针灸是CSA主要疗法之一，目前理论研究主要侧重于椎动脉血管宏观形态和血液流速观测。我们及前人研究发现，电针可增加血管增生重要信号分子基质细胞衍生因子的表达，电针可通过激活磷脂酰肌醇3-激酶（PI3K）和蛋白激酶B（AKt）实现损伤组织血管再生。但电针是否通过基质细胞衍生因子介导的PI3K/AKt信号通路来治疗CSA尚无相关研究。本课题建立CSA兔模型，从宏观和微观观察电针对CSA兔椎动脉血流动力学和微观形态结构的影响，采用蛋白质印迹、逆转录-聚合酶链式反应(RT-PCR)和甲基化特异性PCR等技术探讨基质细胞衍生因子介导的PI3K/AKt/mTOR信号通路参与CSA发生发展的分子机制以及电针的可能调控途径。本研究将从较深层次较新角度阐述电针对CSA的作用机理，并将有助于推动针灸广泛应用于颈椎病的治疗。

为探讨电针对椎动脉型颈椎病（Cervical Spondylosis of vertebral Arterytype, CSA）的治疗作用和关键机理，本研究观察了电针对CSA模型兔的治疗作用，探讨了电针对SDF-1/CXCR4介导的PI3K/Akt/mTOR信号通路的调控机制。结果显示电针对CSA模型兔有较好的干预效应，对椎动脉SDF-1/CXCR4 mRNA和蛋白表达均具有调控作用，说明电针的治疗作用通过对SDF-1/CXCR4的干预途径。实验同步观察到电针对CSA模型兔椎动脉中PI3K/Akt/mTOR也具有一定的调控作用，说明电针调控SDF-1/CXCR4与对PI3K/Akt/mTOR的干预存在相关性。在此基础上，观察了电针对CSA模型兔椎动脉血管微观形态与孔径分布的影响，发现电针治疗后，椎动脉表面增生了较多的微血管，同时微孔增加，有利于营养成分的输送，暗示了电针治疗CSA的机理可能与此相关。本研究对揭示电针治疗CSA的关键机理提供了科学依据，有助于推动电针疗法更加广泛地应用于CSA的治疗。