研究CEA术的脑血流动力学变化及斑块稳定性

发布时间：2018-04-19 17:03

本文选题：经颅多普勒 + 颈动脉内膜剥脱术　；参考：《苏州大学》2014年硕士论文

【摘要】：本课题包括两个部分：（1）研究颈动脉内膜剥脱术（carotid endarterectomy, CEA）中脑血流动力学变化；（2）研究CD40及基质金属蛋白酶（matrix metalloproteinases,MMPs）在CEA斑块中的表达及对斑块稳定性的影响。第一部分研究颈动脉内膜剥脱术中脑血流动力学变化目的运用经颅多普勒超声（transcranial doppler, TCD）在CEA术中实时监测脑血流动力学变化，对如何防止脑缺血及过度灌注进行前瞻性研究。方法29例（35例次）接受CEA治疗的颈动脉狭窄患者，分为双侧狭窄组（双侧颈动脉中-重度狭窄或一侧闭塞）及单侧狭窄组。设定TCD监测指标调控血压：临时阻断颈动脉后（临阻后），手术侧大脑中动脉（middle cerebral artery, MCA）平均血流速度（mean blood flow velocity, Vm）低于临阻前的70%，则提升血压；解除临阻后，手术侧MCAVm超过临阻前的100%，则降低血压。手术前、后头颈部血管均行TCD、彩色多普勒血流显像（color doplor flow image, CDFI）、磁共振血管成像（magneticresonance angiography, MRA）和/或CT血管造影（computed tomography angiography,CTA）和/或数字减影血管造影（digital subtraction angiography, DSA）检查，判断血管的狭窄程度及再通状况；行CT灌注成像（computed tomography perfusion, CTP）评判脑灌注状况；行计算机体层摄影（computerized tomography, CT）及磁共振成像（magnetic resonance imaging, MRI）评判脑实质有无出血或缺血改变；术前行TCD检查以判断侧枝循环。结果（1）两组患者：临阻前，手术侧MCAVm较麻醉前减低（P=0.000）；临阻后，MCAVm略低于临阻前（P0.05），血压提升（23.76±9.15）%（P=0.000）；解除临阻后，MCAVm较临阻前增高（P=0.000），血压降低（6.70±6.89）%（P=0.000）。（2）两组间比较：临阻后，双侧狭窄组手术侧MCAVm较单侧狭窄组减低（P0.05），血压提升幅度较单侧狭窄组大（P0.01）；解除临阻后，双侧狭窄组血压降低幅度较单侧狭窄组小（P0.05），两组间MCAVm差异无统计学意义（P0.05）。（3）预后：患者脑灌注均改善，神经功能得到不同程度的改善。结论TCD在CEA术中实时监测脑血流动力学变化，评估脑灌注，指导麻醉调控血压，能显著提高手术成功率。第二部分研究CD40及MMPs在CEA斑块中的表达及对斑块稳定性的影响目的研究CD40及MMPs在颈动脉易损斑块及稳定斑块中的表达，探讨CD40与MMPs表达的相关性及影响斑块稳定性的可能机制。方法收集CEA术后的粥样硬化斑块标本35例次，根据术前CDFI检查判断斑块性质、TCD检查是否监测到微栓子信号（microembolic signals, MES）及是否发生急性缺血性卒中事件，将患者分为易损斑块组及稳定斑块组。采用实时荧光定量聚合酶链反应（realtime fluorescent quantitative PCR, Realtime PCR）和免疫印迹法（Westernblotting）检测两组标本中CD40及MMPs（MMP-1、MMP-2、MMP-9、MMP-14）的mRNA和蛋白表达水平。结果（1）Realtime PCR检测结果：易损斑块组CD40和MMP-9mRNA表达水平较稳定斑块组显著增高（P0.01），两组间MMP-1、MMP-2、MMP-14mRNA表达水平的差异无统计学意义（P0.05）；通过相关性分析，CD40mRNA与MMP-9mRNA之间呈显著正相关（r=0.9006，P0.0001），CD40mRNA与MMP-2mRNA之间呈正相关（r=0.4322，，P=0.0135），但CD40mRNA与MMP-1mRNA（r=0.0282）、CD40mRNA与MMP-14mRNA（r=0.0876）之间无明显相关性（P0.05）；（2）Western blotting检测结果：鉴于易损斑块组CD40mRNA与MMP-9mRNA的表达显著高于稳定斑块组，且CD40mRNA与MMP-2mRNA、CD40mRNA与MMP-9mRNA之间呈正相关，因此，选取CD40、MMP-2及MMP-9进一步进行蛋白水平分析，结果提示：易损斑块组CD40、MMP-2及MMP-9的蛋白表达量均较稳定斑块组明显增高。结论CD40不仅参与动脉粥样硬化斑块的形成，而且可能通过调控MMP-2、MMP-9的表达影响动脉粥样硬化斑块的稳定性，促进斑块破裂，造成缺血性卒中的发生。
[Abstract]:This topic includes two parts: (1) the study of cerebral hemodynamic changes in carotid endarterectomy (CEA); (2) the study of the expression of CD40 and matrix metalloproteinase (matrix metalloproteinases, MMPs) in CEA plaque and the effect on the stability of plaque.
The first part is to study the changes of cerebral hemodynamics during carotid endarterectomy.
Objective using transcranial Doppler (TCD) to monitor the changes of cerebral hemodynamics in real time in CEA, and to investigate how to prevent cerebral ischemia and overperfusion.
Methods 29 cases (35 cases) of carotid stenosis treated with CEA were divided into bilateral stenosis group (bilateral carotid - severe stenosis or unilateral occlusion) and unilateral stenosis group. The TCD monitoring index was set to regulate blood pressure: temporary occlusion of the carotid artery (post obstruction), and the mean blood flow velocity of the middle cerebral artery (MCA) on the operative side (mean B). Lood flow velocity, Vm) was lower than 70% before obstruction, and the blood pressure was raised. After the removal of impaction, the operating side was 100% before the obstruction, and the blood pressure was reduced. Before the operation, the blood vessels of the head and neck were all TCD, color Doppler flow imaging (color Doplor flow image, CDFI), magnetic resonance angiography (magneticresonance), and / or blood. Computed tomography angiography (CTA) and / or digital subtraction angiography (digital subtraction angiography, DSA) were used to determine the degree of stenosis and repassage of blood vessels. The perfusion of CT perfusion imaging (computed tomography perfusion) was used to evaluate the cerebral perfusion status. Magnetic resonance imaging (MRI) was used to assess whether there was hemorrhage or ischemia in the parenchyma of the brain. Preoperative TCD examination was performed to identify collateral circulation.
Results (1) two groups of patients: MCAVm before anesthesia was lower than before anesthesia (P=0.000); after obstruction, MCAVm was slightly lower than before obstruction (P0.05), blood pressure was raised (23.76 + 9.15)% (P=0.000);
After blocking, MCAVm increased (P=0.000) and blood pressure decreased (6.70 + 6.89)% (P=0.000).
(2) comparison between the two groups: after the obstruction, the operative side of the bilateral stenosis group was lower than that of the unilateral stenosis group (P0.05), and the blood pressure elevation was larger than that of the unilateral stenosis group (P0.01). After the termination of the impending obstruction, the decrease of blood pressure in the bilateral stenosis group was smaller than that of the unilateral stenosis group (P0.05), and the difference between the two groups was not statistically significant (P0.05). (3) the prognosis of the patients in the two groups was (P0.01). Good, neural function is improved in different degrees. Conclusion TCD can monitor cerebral hemodynamic changes in real time in CEA, evaluate cerebral perfusion and guide the control of blood pressure by anesthesia, and can significantly improve the success rate of operation.
The second part is to study the expression of CD40 and MMPs in CEA plaques and its effect on plaque stability.
Objective to investigate the expression of CD40 and MMPs in vulnerable plaques and stable plaques of carotid artery, and to explore the correlation between CD40 and MMPs expression and the possible mechanism of plaque stability.
Methods 35 cases of atherosclerotic plaque after CEA were collected. The properties of plaque were determined by CDFI examination before operation. TCD detected the micro embolus signal (microembolic signals, MES) and the occurrence of acute ischemic stroke. The patients were divided into vulnerable plaque group and stable plaque group. Real time fluorescence quantitative polymerase chain reaction (RT) was used. Realtime fluorescent quantitative PCR, Realtime PCR) and immunoblotting (Westernblotting) were used to detect the levels of CD40 and MMPs (MMP-1, MMP-2, MMP-9, and proteins) in two groups of specimens.
Results (1) Realtime PCR detection results: the expression level of CD40 and MMP-9mRNA in vulnerable plaque group was significantly higher than that in the stable plaque group (P0.01). There was no significant difference in the expression level of MMP-1, MMP-2, MMP-14mRNA between the two groups (P0.05). The correlation analysis showed that the CD40mRNA and MMP-9mRNA were positively correlated (r=0.9006,) There is a positive correlation between RNA (r=0.4322, P=0.0135), but there is no significant correlation between CD40mRNA and MMP-1mRNA (r=0.0282), CD40mRNA and MMP-14mRNA (r=0.0876). (2) Western blotting detection results: the expression of vulnerable plaque group and the expression of the plaque is higher than that of the stable plaque group. There is a positive correlation between CD40, MMP-2 and MMP-9. The results suggest that the protein expression of CD40, MMP-2 and MMP-9 in vulnerable plaque group is higher than that of the stable plaque group. Conclusion CD40 not only participates in the formation of atherosclerotic plaque, but also may affect the atherosclerotic atherosclerotic atherosclerosis by regulating the expression of MMP-2. The stability of atherosclerotic plaque promotes plaque rupture and causes ischemic stroke.

【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R743.3

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