中文摘要
脑梗死具有发病率高、死亡率高、致残率高的特点,除溶栓外,尚无有效西药。以益气通阳活血或清热解毒通络为主要治法的中药,对脑梗死治疗具有一定优势。然而,两种治法,一者助阳为主,一者清热为主,看似相反,却都能起效,其同病异治的内在机制是什么?自噬是脑梗死的重要病理机制之一,对自噬的动态双向调节是抗脑缺血药理研究的热点方向,上述两种治法代表性中药对自噬表现出不同的调节作用。于是提出假说:不同时间点对神经细胞自噬的双向调节可能是两种治法对脑梗死同病异治的内在机制。本课题采用脑缺血大鼠和氧糖剥夺神经细胞模型,选用3种中药注射液代表上述两种治法,比较其在缺血/缺氧后不同时间点对神经细胞自噬的调节作用;联用自噬抑制剂和诱导剂,分析其调节自噬与抗脑缺血药效的关联性;检测相关通路蛋白,揭示其调节自噬的具体通路。由此可围绕自噬调节途径阐明两种治法对脑梗死同病异治的科学内涵,为脑梗死临床方案优化提供参考。
英文摘要
Cerebral infarction is characterized by high morbidity, mortality and disability rate, which cannot be treated effectively by western medicine besides thrombolytic therapy. However, traditional Chinese medicine has certain advantages in treating cerebral infarction with the effect of YiqiTongyangHuoxue(invigorating qi, and activating yang and blood circulation)and QingreJieduTongluo(clearing heat, removing toxicity and dredging collaterals). The therapies of invigorating qi and clearing heat seem to have opposite efficacy, but both of them work. Then what is the underlying mechanism of the different therapies in treating the same disease?Is it related to the dynamic bidirectional regulation on autophagy? The answers of the above questions will help to understand the mechanism of traditional Chinese medicine in treating cerebral infarction, and has significance to improve the efficacy. The present subject choosesSailuotongcapsule and Tongluoqingnao injection, standing for the therapy of YiqiTongyangHuoxue and QingreJieduTongluo respectively. Through cerebral ischemic animal model and cell experiments in vitro, their intervention effects on neuronal autophagy are observed after ischemia and anoxiaat different time points. Autophagy inhibitor and inducer are used jointly to analyze the relevance between the regulation effect of traditional Chinese medicine on autophagy and the efficacy against cerebral ischemia. The related protein expression is tested to partly reveal the specific pathways of autophagy regulation. Thus, it is possible to explain the correlation between the efficacy against cerebral ischemia and the regulation effect of the medicine, to discuss the underlying mechanism of the different therapies in treating cerebral infarction, and to provide valuable reference for optimizing TCM treatment of cerebral infarction.
