Wnt/Dvl/β-catenin通路在腺苷A1R介导电针诱导脑缺血耐受中的作用及机制研究

电针能有效治疗缺血性脑卒中，但分子机制有待阐明。课题组前期发现腺苷A1R和Wnt通路下游β-catenin均介导了电针诱导的脑缺血耐受（CIT）。研究进一步发现A1R激动剂CCPA影响Wnt通路上游Dvl及GSK-3β，Dvl沉默后逆转了CCPA的细胞增殖。我们从Wnt/Dvl/β-catenin通路角度推测：电针激活A1R发挥激酶作用，诱导Dvl磷酸化，上膜形成Dvl/LRP6信号小体，促使β-catenin集聚向胞核转位，产生CIT。本研究拟解决：1.阐明EA激活A1R，Dvl磷酸化上膜，结合LRP6形成Dvl/LRP6信号小体；2.阐明Wnt/Dvl/β-catenin通路是A1R介导电针CIT的必要条件。从整体、组织、细胞、分子、基因水平，首次论证Wnt/Dvl/β-catenin通路在A1R介导电针诱导CIT的作用及机制，为中医脑保护研究提供科学依据。

Electroacupuncture can be effective in the treatment of cerebral ischemia, but the molecular mechanism remains to be elucidated. Our previous studies have found both adenosine A1 receptor and β-catenin in Wnt/β-catenin pathway mediate cerebral ischemic tolerance induced by electroacupuncture. Other study shows adenosine A1 receptor agonist (CCPA) influences Dvl protein and GSK-3β, and silencing Dvl protein reverses the effect of CCPA in cell proliferation. We infer from the Wnt / Dvl / β-catenin pathway that electroacupuncture activates A1 receptor which induces Dvl phosphorylated onto membrane,which helps the form of Dvl / LRP6 signalingand acting as a key to promote the translocation of β-catenin into the nucleus resulting CIT. The aim of our study is to clarify that:1.To clear that electroacupuncture activate A1R,which helps Dvl protein phosphorylatthed into Dvl/LRP6 signalingand.2.To clear that Wnt/Dvl/β-catenin pathway is necessary to the CIT by A1R-mediated electroacupuncture. With the level of whole, tissue, cell, molecule and gene,we demonstrate firstly the effect and mechanism of Wnt/β-catenin pathway,which cause CIT mediated with electroacupuncture induced by adenosine A1 receptor.The study will give the scientific basis for the traditional Chinese medicine in the brain protection.