活血化瘀类中药对大鼠脑缺血再灌损伤的作用差异及基因调控研究

Ginkgo biloba extract, Panax notoginseng saponins, and Scutellarin are typical representative Chinese herbs of Huoxuehuayu which are widely used to treat ischemic cerebral vascular diseases in clinical in China, but their efficacies and safeties are not tested by qualified clinical trials, or it was controversial between different clinical trials, it was also not reported the characters and differences among them, and their mechanisms are not so clear, which is brought quite a big difficult to choose and use these herbs reasonably. Our study is depended on brain ischemic reperfusion injury model of rats (MCAO model), and focused on oxidative stress, apoptosis, inflammation, from body symptoms, biochemical and molecular biomarkers in serum and tissues to gene regulatory, simultaneously and systematically studying the characters and differences among these three herbs in the same doses or equal efficacy doses to clinical usage doses in man, and farther observing the effects of these herbs on regulatory genes TLR-2/4 、Nrf2、Bcl/Bax and miRNA in brain ischemic reperfusion injury of rats, for uncovering the mechanisms of gene regulatory of these three herbs on brain ischemic reperfusion injury in rats. The results of our study will provide very important experimental bases for choose and use these three herbs reasonably, and find new actions and new mechanisms of these herbs.

活血化瘀类中药银杏叶提取物、三七总皂苷和灯盏乙素是国内临床上广泛用于治疗缺血性脑血管疾病的典型代表药物，但其有效性和安全性并未经可靠的临床试验所证实，或临床试验结果互相矛盾，它们间的作用特点和作用差异也未见报道、作用机制也未完全阐明，这给临床如何选择和合理使用这些药物带来相当大的困难。本项目拟以大鼠脑缺血再灌损伤模型（MCAO法）为研究对象，以氧化应急、凋亡、炎症三途径，从表征、血清和组织生化与分子标记物、基因调控等方面研究入手，同步、系统深入研究这三种药物在相同剂量和等效剂量下：它们对大鼠脑缺血再灌损伤的作用特点和差异；并进一步观察它们对脑缺血再灌损伤调控基因TLR-2/4 、Nrf2、Bcl/Bax和miRNA的影响，以阐明这三种活血化瘀药物对脑缺血再灌损伤作用的基因调控机制。研究结果可为临床合理选择和使用这三类药物提供重要的实验依据、并发现它们新的作用和作用机制。

活血化瘀类中药银杏叶提取物、三七总皂苷和灯盏乙素是国内临床上广泛用于治疗缺血性脑血管疾病的典型代表药物，但其有效性和安全性并未经可靠的临床试验所证实，或临床试验结果互相矛盾，它们间的作用特点和作用差异也未见报道、作用机制也未完全阐明，这给临床如何选择和合理使用这些药物带来相当大的困难。我们以大鼠脑缺血再灌注损伤（I/R）模型（MCAO模型）为研究对象，研究发现预防性给予（一日一次，腹腔注射，共7日）或治疗性给予（一日一次，尾静脉注射临床等效剂量，共7日）银杏叶提取物（金纳多）、三七总皂苷（血塞通）和注射用灯盏花素（主要成分为灯盏乙素）均不能降低大鼠脑I/R后死亡率，但可改善脑梗死体积或行为学评分，但低剂量效果一般、适当的加大剂量有益治疗、但随剂量的增加死亡率也增加。预防性给予等剂量的金纳多和血塞通，疗效无明显差异，治疗性给予临床等效剂量，三药疗效无明显差异。它们共同的机制可能与NO和抗氧化有关。灯盏花素的作用机制还可能与调节纤溶功能、抗炎症有关，通过miRNA、CYP4A等基因调控I/R损伤。三七总皂苷（血塞通）的作用机制则主要与扩血管作用以及对抗血栓生成、抗炎症有关，通过miRNA、CYP、TLR4、PI3-K等基因多途径调控I/R损伤。我们的研究发现可为临床合理选择和使用这些中药提供重要的实验依据。