伴颅内动脉狭窄急性缺血性脑血管病进展复发的动脉粥样硬化稳定性、血栓形成及脂代谢通路分子机制研究

The proportion of intracranial arterial stenosis (ICAS) in ischemic cerebrovascular disease was 46.6%. In previous studies, we found that the rate of the progression and stroke recurrence was 12.5% in ICAS followed by 3 months; and the level of hsCRP were significantly associated with ICAS and ischemic stroke recurrence. To further reveal the immune molecular mechanism of the progression and stroke recurrence in ICAS, we use the clinical data and sample in the repository of Chinese National Stroke Registration-Ⅲ study, and the degrees of intracranial artery stenosis are assessed according to the brain MRA/CTA, and focus on the prediction of three molecular pathways: atherosclerotic plaque stability, thrombosis and lipid metabolism on the prognosis of ICAS. Using protein microarra, immunoturbidimetry and mass spectrum, we detect the dynamic expressions of protein levels and gene polymorphism sites of proteomics in order to find the molecular markers related to the progression and stroke recurrence in ischemic stroke and TIA with ICAS. And we explore the relationship between the dynamic changes of blood molecules and the prognosis of ICAS. From protein and gene levels, we analyze the different molecular mechanisms of the progression and stroke recurrence in ICAS. Next, we will build risk prediction model for ischemic cerebrovascular disease based on molecular markers compared with clinical rating scale (such as Essen, ABCD2) by ROC, taxonomy and quasi and statistical methods. These findings will provide theoretical basis for secondary prevention strategies and early therapeutic targets for ischemic cerebrovascular diseases with ICAS.

动脉粥样硬化导致的颅内动脉狭窄(ICAS)占缺血性脑血管病的46.6%；前期研究发现ICAS进展复发率为12.5%，且hsCRP与ICAS及卒中复发相关。为进一步揭示ICAS进展复发的分子机制，我们利用中国国家卒中登记-Ⅲ的临床资料及样本资源库，尤其根据头MRA/CTA评估颅内动脉狭窄情况，重点研究动脉粥样硬化斑块稳定性、血栓形成及脂代谢通路对ICAS预后的预测作用，采用免疫比浊法、蛋白芯片及质谱等方法检测相关分子标记物蛋白动态表达及基因多态性位点：寻找与伴ICAS脑梗死/TIA进展复发密切相关的分子标记物；探索血分子动态变化与ICAS预后的关系；从蛋白和基因表达水平分析ICAS进展复发的分子机制；与临床评分量表(如Essen、ABCD2)结合, 通过ROC法、重分类法及拟和优度等统计方法，构建基于不同分子通路的伴ICAS脑梗死/TIA高危预测模型，为ICAS的防治提供理论依据。

背景 动脉粥样硬化导致的颅内动脉狭窄(ICAS)占缺血性脑血管病的46.6%；前期研究发现I CAS进展复发率为12.5%，且hsCRP与ICAS及卒中复发相关。.主要研究内容 利用中国国家卒中登记-Ⅲ的临床资料及样本资源库，尤其根据头MRA/CTA评估颅内动脉狭窄情况，重点研究动脉粥样硬化斑块稳定性、血栓形成及脂代谢通路对ICAS预后的预测作用，采用免疫比浊法、蛋白芯片及质谱等方法检测相关分子标记物蛋白动态表达及基因多态性位点；寻找与伴ICAS脑梗死/TIA进展复发密切相关的分子标记物；探索血分子动态变化与ICAS预后的关系；从蛋白和基因表达水平分析ICAS进展复发的分子机制；与临床评分量表结合, 构建基于不同分子通路的伴ICAS 脑梗死/TIA高危预测模型。.重要结果 急性脑梗死/TIA患者的纤维蛋白原及低密度脂蛋白水平与卒中复发相关，纤维蛋白原、D-二聚体、白蛋白、胆红素及血红蛋白水平与患者功能不良结局相关，高同型半胱氨酸和超敏C-反应蛋白水平与认知功能损害相关。.关键数据 发病90天纤维蛋白原水平高于发病7天内（443.5 mg/dl vs 393.7 mg/dl）；纤维蛋白原水平和功能不良(OR, 1.46; 95% CI, 1.07–2.00)及残疾结局(OR, 1.43; 95% CI, 1.03–1.98)独立相关；D-二聚体水平和全因死亡（HR, 1.77; 95% CI, 1.25–2.52）及功能不良（OR, 1.49; 95% CI, 1.23–1.80）独立相关；低密度脂蛋白C水平和卒中复发相关(OR, 1.02; 95% CI, 1.00-1.03)。.科学意义 阐明了凝血因子及脂代谢分子与卒中临床结局相关，探讨卒中复发和功能不良的分子机制，为寻找卒中不良结局的精准治疗靶点提供依据。