急性轻型卒中/短暂性脑缺血发作病情进展和卒中复发的分子机制研究 - - -基于CHANCE研究的亚组分析

项目名称： 急性轻型卒中/短暂性脑缺血发作病情进展和卒中复发的分子机制研究 - - -基于CHANCE研究的亚组分析

项目编号： No.81471211

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王拥军

作者单位： 首都医科大学

项目金额： 80万元

中文摘要： 轻型卒中和TIA是最常见的脑血管病亚型，我们前期的多中心随机对照双盲临床试验（CHANCE研究）发现，即使坚持服用阿司匹林或氯吡格雷联合阿司匹林治疗，仍然有部分患者出现了卒中复发。为此我们对该研究血样亚组共3193例患者血清样本检测了24种蛋白标记物，初步结果显示，和炎症、动脉粥样硬化斑块稳定性相关的hsCRP、sCD40L和缺血性脑卒中复发显著相关；近期研究提示卒中进展和复发存在不同机制。为进一步揭露轻型卒中和TIA病情进展和卒中复发的分子机制，本课题拟利用CHANCE研究临床资料及样本资源库，采用蛋白芯片进一步扩大检测的炎症、动脉粥样硬化斑块稳定性相关的蛋白谱，从而发现轻型卒中/TIA进展及复发的生物标记物；将其与Essen/ABCD2临床评分量表结合, 通过ROC法、重分类法及拟和优度等统计方法，构建基于生物标记物的轻型卒中/TIA高危预测模型。

中文关键词： 轻型缺血性脑卒中；短暂性脑缺血发作；病情进展；卒中复发；分子机制

英文摘要： Minor stroke and transient ischmic stroke (TIA) are the most common subtypes of cerebrovascular diseases. Our primary study, the multicenter randomized double-blind clinical trial Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE), indicated ischemic stroke recurrence even arised in patients sticking with anti-platelet therapy. The subsequent subgroup study included 3193 serum samples of the patients in CHANCE trial and 24 biomarkers were screened. The preliminary results showed hsCRP、sCD40L, which were associated with inflammation and instability of carotid plaque, independently predicted ischemic stroke recurrence. Some recent research suggested there were different mechanisms leading to progression and stroke recurrence. In order to reveal the molecular mechenisms for progression and ischemic stroke recurrence in minor stroke and TIA, the clinical database and biobank of CHANCE trial would be used. Not only extended protein expression profiling related to inflammation and instability of carotid plaque would be screened via protein microarray, but neuropeptide would also be detected through chemiluminesent immunoassay assay. The selected biomarker would be combined with Essen/ABCD2 score. Thereafter, high-risk prediction model for minor stroke and TIA based on biomarker would be built up by using ROC、reclassification methods and goodness of fit test.

英文关键词： minor stroke;TIA;progression;stroke recurrence;molecular mechanisms