基于“脑肝筋轴”从CCR5/CREB-突触可塑性探讨脑梗死后痉挛性瘫痪CRT过度兴奋机制及白芍络石方干预作用

脑卒中是全球目前致残和致死的第1位疾病，脑梗死后痉挛性瘫痪（PSS）是其常见并发症，但发病机制不清。皮质-网状脊髓束（CRT）过度兴奋是PSS发生的核心环节，突触可塑性不良导致CRT过度兴奋，近期发现CCR5/CREB是改善突触可塑性的关键通路。结合前期基础，我们推测：脑梗死后，CCR5/CREB介导突触可塑性不良，CRT过度兴奋，引起脊髓运动神经元兴奋性增加是PSS发生的根本原因。本项目拟以PSS大鼠模型、糖氧剥夺CRT共培养模型为研究对象，结合病毒基因调控、神经示踪、膜片钳、透射电镜及免疫荧光等方法，从在体、离体两方面，揭示“CCR5/CREB-突触可塑性不良介导的CRT过度兴奋导致PSS发生”的分子机制，并采用“脑肝筋轴”指导下养血柔肝、舒筋通络立法的白芍络石方干预，反证中医“脑肝筋轴”病机理论。该研究对于揭示PSS的发病机制，明确中医药防治PSS的靶点有着重要意义。

Stroke is the first leading cause of mortality and disability worldwide, and post-stroke spasticity (PSS) is the common complication which the pathogenesis is unclear. The hyperexcitability of cortico-reticulospinal tract (CRT) is the primary process of PSS. Recent studies have revealed that CCR5/CREB pathway can improve the synaptic plasticity, which maladaptive synaptic plasticity leads to the hyperexcitability of CRT. Based on the previous researches, we hypothesize that: the hyperexcitability of CRT induced by CCR5/CREB-synaptic plasticity is the key cause for PSS. This project aims to use gene silence, gene knockout, neural tracing, patch clamp, TEM and immunofluorescence, revealing the mechanism of CRT hyperexcitability induced by CCR5/CREB-synaptic plasticity in vivo and in vitro. Baishaoluoshi Decoction of nourishing blood and emolliating liver as well as Shujintongluo is applied as a counterevidence to clarify and enrich the scientific connotation of “brain-liver-fascial axis”. This research is of great significance for revealing the pathogenesis of PSS and clarifying the target of TCM to prevent and treat PSS.