脑白质疏松与后循环缺血及脑血管功能的相关性研究

The age-related leukoaraiosis (LA) is a kind of non-specific white matter lesions, which often serves as a surrogate marker of the progression of cerebral small vessel disease (cSVD). As the imaging technique develops, this sort of LA is highly detected, but with its pathogenesis poorly understood. It is speculated to be closely associated with the vascular factors, such as chronic ischemia and breakdown of blood-brain barrier; However some studies demonstrated no significant correlations between the results of static cerebral hemodynamic measurements (such as resistance index and cerebral blood flow) and the severity of LA, indicating the former indexes might not be reliable in reflecting the alteration of cerebrovascular function, which is most likely to be already impaired in cSVD. Animal studies showed the impairment of cerebrovascular function is involved in the pathogenesis of LA. In this regard, some human studies have examined the cerebrovascular function in patients with LA, but with conflicting results; moreover, most of them assessed the cerebrovascular function only in anterior (the territory supplied mainly by the internal carotid arteries) but not in posterior (the territory supplied mainly by the vertebral arteries) circulation. Considering the high incidence and importance of posterior circulation ischemia (PCI), this project is aimed to assess and compare the anterior and posterior cerebrovascular functions by using color duplex-Doppler ultrasonography (CDUS), to evaluate their relationships with the LA and PCI, to test the hypothesis that the impact of cSVD on the progress of LA is mediated by the impaired cerebrovascular function, and to explore sensitive and reliable cerebrovascular functional indexes in assessing the pathogenesis and severity of LA and PCI.

年龄相关性脑白质疏松（leukoaraiosis, LA）是脑小血管病（cerebral small vessel disease, cSVD）的典型影像学表现，随着影像学技术的进步，其检出率明显增高，但发病机制仍不十分清楚，多认为与慢性缺血和血脑屏障破坏等血管因素有关，然而以往研究较多的静态脑血流参数并不能敏感地反映cSVD时很可能已经受损的脑血管功能，而后者很可能才是cSVD致LA的重要机制。目前虽已有研究开始关注LA时的脑血管功能，但结果并不一致，且多只局限于前循环（颈内动脉系统）而很少涉及后循环（椎动脉系统）。鉴于后循环缺血（posterior circulation ischemia, PCI）的多发性及重要性，我们拟应用彩色双功能超声评估比较前、后循环的脑血管功能，明确其与LA 和PCI之间的关系，为分析LA和PCI的发病机制及病情提供脑小血管病变及功能方面的依据和评估指标。

近些年来发展起来的血管彩色双功能多普勒超声在脑血流灌注和脑血流调节功能方面有重要的科研和临床应用价值，并肯定有利于高原医学领域中缺氧环境下脑血流调节功能评估及其机制的研究。本课题率先通过横断面数据采集研究分析发现不论在高原地区还是平原地区，藏族人群的全脑血流和全脑供氧量均要明显低于同海拔组的汉族人群；进一步的实验生理研究也表明，藏族人群的脑血流和脑供氧量对常规临床剂量的吸氧也较汉族人群成钝化反应；而各种族在同海拔地区（高原或平原）的长期环境适应（2-5年）并不能减少这种差异性。这些结果提示世居高原人群（藏族）与世居平原人群（汉族）对氧浓度/分压变化的脑血流调节存在不受适应长短影响的先天差异性，使得他们获得各自适宜于高原或平原地区的脑血流稳态和调节模式。本研究实验设计科学数据可靠，其结果纠正了过去的一些错误认识，比如单纯将缺氧时脑血流增加和反应增强作为脑缺氧耐受性的生理评估是不科学的，而事实很可能是如果脑细胞有更好的缺氧耐受机制，它本身并不需要通过被动增加更多的脑血流量来满足对氧气的需求，而最近有文献表明过多的脑血流其实往往与一些高原适应不良和神经系统症状相关联。本研究结论有利于正确科学评估高原或缺氧条件下脑血流及调节功能的临床意义，对脑缺氧耐受能力的研究也有重要参考价值。