动脉粥样硬化斑块滋养血管紧张度增加对斑块易损性的影响及其机制的研究

Vulnerable plaque rupture is the main reason of the clinical cardiovascular events, therefore, intense research about its mechanism and influence factors is of vital importance. Previous studies have shown that hypoxia plays an important role in the formation and progression of vulnerable plaque. Hypoxia can increase plaque vulnerability by multiply mechanism including promoting the formation of neovessels and accelerating inflammation. Vasa vasorum of plaque, a part of systemic vascular, displays a small artery-like structure. This characteristic is important since it imply the vasa vasorum may expand or contract under the influence of varies vasoactive substances to adjust blood oxygen supply of plaque. Our previous study have shown that vasa vasorum tensity can be adjusted by various vasoactive substances, however, research about the role of vasa vasorum tensity in plaque vulnerability was absent. Based on the effect of hypoxia on plaque vulnerability and our previous study, we hypothesize that increase of plaque vasa vasorum tensity is likely to affect plaque vulnerability by a series of mechanism including hypoxia. Therefore, the present study was designed to assess plaque blood volume change after administration of noradrenalin on plaque vulnerability by using contrast-enhanced ultrasonography results and comparison with serological markers and pathological dyeing expression of hypoxia and inflammation. Our study will provide experiment basis for research about the influence factors and mechanism of plaque vulnerability.

易损斑块破裂是临床心脑血管事件发生的主要原因，因此，深入研究斑块的易损性形成机制及影响因素具有重要的意义。以往研究发现缺氧在易损斑块形成及发展过程中起到了非常重要的作用，其可以通过促进新生血管形成，加速斑块的炎症反应等多种机制增加斑块的易损性。斑块的滋养血管作为全身血管的一部分，具有类似小动脉的结构，因而可能会受体内各种血管活性物质的影响而发生收缩或舒张以调节斑块的血氧供应。我们之前的研究发现滋养血管紧张度受血管活性物质调节，但是，有关滋养血管紧张度对斑块易损性影响的研究尚属空白。基于缺氧对斑块易损性的影响及我们之前的研究，提出假设：斑块滋养血管紧张度增加有可能通过缺氧等一系列机制影响斑块易损性。为此，本项目将应用超声造影成像方法观察滋养血管紧张度增加后斑块血容量的变化情况，对比缺氧和炎症血清学标志物及病理染色结果分析其对斑块易损性的影响，为斑块易损性的影响因素及其机制研究提供实验依据。

易损斑块破裂是临床心脑血管事件发生的主要原因，因此，深入研究斑块的易损性形成机制及影响因素具有重要的意义。以往研究发现缺氧在易损斑块形成及发展过程中起到了非常重要的作用，其可以通过促进新生血管形成，加速斑块的炎症反应等多种机制增加斑块的易损性。斑块的滋养血管作为全身血管的一部分，具有类似小动脉的结构，因而可能会受体内各种血管活性物质的影响而发生收缩或舒张以调节斑块的血氧供应。我们之前的研究发现滋养血管紧张度受血管活性物质调控，但是，有关滋养血管紧张度对斑块易损性影响的研究尚属空白。基于缺氧对斑块易损性的影响及我们之前的研究，本项目应用超声造影成像方法观察滋养血管紧张度增加后斑块血容量的变化情况，对比缺氧和炎症血清学标志物及病理染色结果分析其对斑块易损性的影响，发现长期多次给予去甲肾上腺素后兔斑块增强强度发现，其增强强度减低（4.91±0.34dB vs 3.77±0.45 dB, p<0.05）。对兔斑块进行了缺氧坏死因子HIF染色，血管内皮生长因子VEGF染色，发现长期给予去甲肾上腺素（noradrenaline，NE ）后斑块的HIF及VEGF表达增多且局限于斑块的外膜层，单次给予或不给予NE的斑块HIF及VEGF表达少且分散在斑块中层。表明长期多次给予去甲肾上腺素后斑块血供减少，斑块发生了缺氧。本研究阐明了滋养血管紧张度增加对斑块稳定性的影响，为斑块易损性的影响因素及其机制研究提供实验依据，具有重要的临床意义及广泛的应用前景。