基于Nogo-A/NgR-Rho/ROCK信号通路探讨电针心包经穴对MCAO大鼠神经修复的调控机制

Acupuncture treatment has become an important treatment for ischemic stroke, pericardium meridian by acupuncture points are also repeated in clinical use, but the mechanism is not clear.Previous studies have shown that electroacupuncture pericardial acupoints can improve neurological symptoms in rats with cerebral ischemia and reduce the expression of Nogo-A in serum and to promote nerve repair to a certain extent. Recent studies have shown that Nogo-A / NgR-Rho / ROCK signaling pathway is an important pathway for mediating inhibitory signaling to block central nervous cell cell regeneration. The activation of this pathway inhibits axonal regeneration. In this study, Nogo-A / NgR-Rho / ROCK signaling pathway was used as the starting point, and the focal cerebral ischemia model (MCAO) was used as experimental carrier. The expression of Nogo-A, NgR1, RhoA, ROCK Ⅱ in the hippocampus of brain tissue was observed by electroacupuncture at the pericardial acupoints. The PSD-95 and SYP were used as the evaluation molecules, The effect of acupuncturing pericardium on nerve repair after cerebral ischemia was explored by dynamic observation at multiple time points, and the experimental basis of pericardium was used to explain the brain.

针灸治疗已成为缺血性脑卒中的重要治疗方法，手厥阴心包经穴位亦在临床中反复使用，但作用机制尚不明确。前期研究显示，电针心包经穴能改善脑缺血模型大鼠神经功能症状，降低血清中Nogo-A因子的表达，一定程度上促进神经的修复。最新研究表明Nogo-A/NgR-Rho/ROCK信号通路是介导抑制性信号阻断中枢神经细胞再生的重要途径，该通路的激活抑制轴突再生。本项目拟以Nogo-A/NgR-Rho/ROCK信号通路为切入点，以局灶性脑缺血大鼠模型（MCAO）为实验载体，电针手厥阴心包经为被试因素，以上肢同节段阴经的手太阴肺经对照，观察电针心包经穴对脑组织海马区Nogo-A、NgR1、RhoA、ROCKⅡ等信号通路中关键分子表达，以PSD-95和SYP为评价分子，通过多时间点动态观察，探究针刺心包经穴对脑缺血后神经修复的影响，阐释运用心包经来从心治脑的实验依据。

针灸治疗已成为缺血性脑卒中的重要治疗方法，手厥阴心包经穴位亦在临床中反复使用，但作用机制尚不明确。前期研究显示，电针心包经穴能改善脑缺血模型大鼠神经功能症状，降低血清中Nogo-A因子的表达，一定程度上促进神经的修复。同时研究表明Nogo-A/NgR-RhoA/ROCKⅡ信号通路是介导抑制性信号阻断中枢神经细胞再生的重要途径，该通路的激活抑制轴突再生。本项目以Nogo-A/NgR-RhoA/ROCKⅡ信号通路为切入点，以局灶性脑缺血大鼠模型（MCAO）为实验载体，电针手厥阴心包经为被试因素，以上肢同节段阴经的手太阴肺经对照，观察电针心包经穴对脑组织缺血区Nogo-A、NgR1、RhoA、ROCKⅡ等信号通路中关键分子表达，以PSD-95和SYP为评价分子，通过多时间点动态观察，探究电针心包经穴对急性脑缺血后上述神经修复相关因子的影响。结果显示电针心包经穴可降低MCAO大鼠神经功能评分，可改善大鼠缺血区脑组织结构，促进神经功能恢复的作用；ELISA检测显示电针心包经穴可不同程度抑制大鼠血清中Nogo-A、NgR1、RhoA、ROCKⅡ的表达，并促进PSD-95和SYP的表达；免疫组化检测、RT-PCR及Western Blot检测也显示电针心包经可不同程度抑制脑组织缺血区的Nogo-A、NgR、RhoA、ROCK等指标mRNA和蛋白的表达，并促进PSD-95和SYP的mRNA和蛋白的表达。因此，电针心包经穴能够通过抑制MCAO大鼠脑组织Nogo-A/NgR1-RhoA/ROCKⅡ信号通路上的关键因子表达，从而保护受损的神经细胞，起到神经修复的作用，但不同的检测和不同指标的检测所表现的有效时间点不同。本研究主要从脑缺血后神经修复的抑制方向入手，探究了针刺心包经穴对脑缺血后神经修复的影响，阐释了运用心包经来从心治脑的实验依据。