双上肢缺血适应防治症状性颅内动脉狭窄脑卒中复发的机制研究

Symptomatic intracrinal arterial stenosis has high morbidity in China, which is the crime culprit of stroke occurrence and recurrenc.Medication and intervention treatment can not stop the stroke occurrence and recurrence completely, and result in poor clinical outcomes or even death. Our more than 10 years of basic researches have confirmed that remote ischemic preconditioning (RIPC)treatment may induce the endogenous protection and relieve the ischemic damage of the brain, and also, the results of our randomized and controlled clinical trial indicated that RIPC may reduce the incidence of stroke recurrent in patients with symptomatic intracrinal arterial stenosis.RIPC is a safe and simple and may be a very promising method on stroke prevention and treatment clinically.However, the mechanismes of the RIPC on stroke prevention in patients with symptomatic intracrinal arterial stenosis are not clear. This study try to make the genomic and protiomic researches to explore the mechanismes of the RIPC on brain protection in patients with intracranial arterial stenosis with the gene chip in combination with the proteomics (SELDI-TOF-MS) after finished two randomized and controlled clinical trials about RIPC on inhibiting stroke occurrence and recurrence（Clinical Trial Registration-URL: NCT01175876 and NCT01321749）,to promote clinical translation of the RIPC on stroke prevention and treatment.

症状性颅内动脉狭窄是缺血脑卒中发生、复发、致死和致残的主要元凶，占我国缺血性脑卒中的35～51%甚至更高，现有治疗（药物和血管内介入）不能完全控制复发，使脑卒中复发和死亡率居高不下，给家庭社会造成重负。我们近10年基础临床研究证实：连续重复双上臂缺血适应(RIPC)能改善脑的血流灌注、降低脑卒中复发率、改善临床预后，是一种无创、廉价、适于临床推广的脑卒中复发防治方法，但脑保护机制、适应症、禁忌症、时机、疗程仍不清楚。我们前期研究显示该方法改善脑血流灌注和神经损伤的机制除涉及AQP-4水通道外可能还涉及多重内源性神经保护，本课题在完成了两项临床随机对照试验（URL:NCT01175876 和 NCT01321749）的基础上，拟通过"基因组学联合蛋白质组学"方法探究其脑保护的分子靶点和机制，为明确治疗适应症、禁忌症、时机和疗程提供依据，促进其临床推广应用。

症状性颅内动脉狭窄导致的慢性脑缺血是缺血脑卒中发生、复发、致死和致残的主要原因，占我国缺血性脑卒中的35～51%甚至更高，现有治疗（药物和血管内介入）不能完全控制复发，使脑卒中复发和死亡率居高不下，给家庭社会造成重负。本研究发现：1）RIPC通过调节血液中tPA和PAI的动态平衡促进血管内纤溶；通过改善深部小血管的血液灌注延缓缺血性脑白质脱髓鞘的进程。2）长期规律地RIPC治疗对hsCRP, WBC, IL-6等免疫炎症因子有一定抑制，有助于降低脑卒中后的炎症反应。提高外周血VEGF水平，促进VEGFR2受体的表达，增加外周血中循环内皮祖细胞数量，可能是其脑保护作用的重要机制。3）研究发现RIPC诱导300余种血浆蛋白表达的变化，其中60余种蛋白的功能涉及炎症抑制、免疫调节和神经保护。.该方法为解决我国颅内动脉硬化性狭慢性脑缺血基础上的脑卒中和血管性认知障碍等难题提供了一种安全、简便、实用、有效、廉价、可推广的非药物方法，尤其对高龄老年患者安全有效。