颅内动脉易损斑块对血流动力学的影响及作用机制研究

Intracranial atherosclerotic stenosis or occlusion is an important etiology of ischemic stroke in Chinese. Hemodynamic changes of stenosis vessels are important factors affecting the prognosis of such patients. With the help of our previous work, we have constructed noninvasive evaluation methodology for intracranial blood flow reserve function. Along the previous work, we aim to further analyse the effect of intracranial plaque characteristic on blood flow reserve function. From patients with intracranial atherosclerosis stroke, intraplaque components will be judged according to the signal intensity over different scan sequences with high-resolution magnetic resonance (MR) imaging technology, and the plaque will be defined as a vulnerable plaque if intraplaque hemorrhage is identified. Based on digital vascular remodeling technology and three-dimensional flow velocity during the whole cardiac cycle measured by 4D flow magnetic resonance technique, fractional flow reserve (FFR) of the involved vessel could be quantificationally calculated from millions of grid data with the whole coupling algorithm. Furthermore, we will quantitatively measure soluble CD40, YKL-40 [Y(tyrosine), K(lysine), L(leucine), 40-kDa] and other inflammatory factors, along with analyse their gene polymorphism. Finally, we attempt to reveal that the vulnerable plaque in patients with intracranial atherosclerotic stroke is one of the independent risk factors for the FFR decreases, and to elucidate the inflammatory factors which mediate the FFR decreases motivated by vulnerable plaques as well as the genetic susceptibility of intracranial vulnerable plaques. It will improve the understanding of arterial plaque characteristic affecting hemodynamic, and provide a theoretical basis to develop new therapy approaches.

颅内动脉粥样硬化性狭窄或闭塞是中国人缺血性卒中的重要病因，狭窄血管的血流动力学变化是影响患者预后的重要因素。我们前期建立了无创颅内血流储备功能评价方法，本项目拟在前期研究基础上，进一步分析颅内动脉管壁斑块性质对血流储备功能的影响。利用颅内动脉粥样硬化性卒中患者，根据高分辨磁共振不同序列信号的强弱判断斑块内成份，如发现斑块内出血则此斑块定义为易损斑块；基于数字化血管重构和4D FLOW磁共振技术测量的全心动周期内三维血流流速，利用超级计算机对百万级网格化数据采用全耦合算法，定量评估狭窄血管的血流储备分数；定量测定血液可溶性CD40、人类软骨糖蛋白等多种炎性因子并分析其编码基因多态性。揭示颅内易损斑块是血流储备分数下降的独立危险因素，进而阐明介导易损斑块引起血流储备分数下降的炎性因子以及易损斑块形成的遗传易感性，为深入理解管壁斑块性质对血流动力学的影响、开发新的治疗方法提供理论依据。

颅内动脉粥样硬化性狭窄或闭塞是中国人缺血性卒中的重要病因，狭窄血管的血流动力学变化是影响患者预后的重要因素。本研究分析了颅内动脉管壁斑块对血流储备功能等血流动力学参数的影响及炎性因子发挥的作用。利用中国国家卒中数据库Ⅲ的数据，基于磁共振-时间飞跃序列原始图像，利用计算流体力学技术，建立了颅内动脉脑血流量、管腔内任意点压力、切应力和狭窄动脉的血流储备分数（狭窄两侧血管内压力比值）等血流动力学参数计算模型，结果发现，动脉管壁切应力的最大值常见于斑块顶点位置和狭窄上游的上半部分，当动脉狭窄≥50%以上时，狭窄率和压力比值呈负相关趋势，尤其重度椎基底动脉狭窄患者，负相关关系更为明显（P<0.05）。在病理生理机制研究中，本研究纳入8006例首发缺血性卒中，按照血浆人类软骨蛋白(YKL-40)浓度分为低浓度组、中浓度组和高浓度组，校正混杂因素后，以低浓度组为对照，中浓度组（OR 1.14，95%CI 0.98-1.34）和高浓度组（OR 1.50，95%CI 1.28-1.76）重度患者（美国国立卫生院卒中量表评分≥8 分）比例更多，检测血YKL-40有助于筛选病重患者。在预后分析中，按YKL-40浓度高低，把患者分为0-33%、34-66%、67-90%和91-100%组,在多变量回归中，调整混杂因素后，91-100%组死亡风险（HR 2.99，95% CI 1.75-5.11）和不良预后结局（OR 1.42， 95% CI 1.08-1.88）较高，入院时YKL-40升高有助于预测缺血性脑卒中后的死亡和不良功能预后。本研究为深入理解动脉斑块对血流动力学的影响，以及从炎性标志物角度对患者病情分层和寻找新的治疗靶点提供了理论依据。