电针对脑缺血灌注期神经元自噬的影响及其机制的研究

Ischemic stroke has been one of the three major causes of human death in recent years. The programmed death of injured neurons was important in the pathophysiologic process of cerebral ischemia and reperfusion (I/R) injury. Different from apoptosis, autophagy was another programmed cell death related to cerebral I/R injury. Autophagy could protect or even exacerbrate neuron injury through mTOR dependent pathway or Beclin1 dependent pathway respectively. Our previous studies found that electroacupuncture could significantly relieve cerebral ischemic injury through enhancing the acitivity of mitochondrial respiratory chain enzyme and inhibiting apoptosis of neurons. We hypothesized that electroacupuncture might inhibit over autophagy so that to relieve mitochondrial injury and cell apoptosis. Therefore, we produced cerebral I/R injury model in rats, to explore the effect of electroacupuncture on neuron autophagy and PI3K-Akt-mTOR signal transduction pathway. This study would clarify the therapeutic mechanisms of electroacupunture in treating cerebral I/R injury and produce new target on preventing ischemic cerebral diseases.

缺血性卒中是目前人类疾病三大死亡原因之一。在脑缺血再灌注（I/R）损伤的病理生理过程中,受损神经元的程序性死亡是重要特征。近来的研究表明，自噬是不同于细胞凋亡的一种程序性细胞死亡，神经元自噬与脑I/R损伤关系密切。自噬可分别通过哺乳动物雷帕霉素靶蛋白（mTOR）依赖通路及Beclin1依赖通路对受损细胞产生保护作用也可加剧损伤。本课题组在前期研究中发现电针能够增强线粒体内呼吸链酶活力，减少线粒体的损伤，抑制神经细胞的凋亡，从而明显减轻脑缺血损伤。我们推测电针可抑制脑I/R时过度自噬所致线粒体等细胞器的损伤，减轻细胞凋亡。为证实这一假说，我们将复制大鼠脑I/R模型，观察电针干预对神经元细胞自噬作用及PI3K-Akt-mTOR信号传导通路的影响。本课题将从新的视角阐明电针抗脑I/R的机制，同时为缺血性脑疾病的防治提供新的靶点。