【作者】 赵峰；

【导师】 薛玉；

【作者基本信息】 江苏大学 ， 影像医学与核医学， 2010， 硕士

【摘要】 背景世界卫生组织(WHO)将脑血管病列为21世纪十大疾病之一。在我国,脑血管病患病率居第3位,其中缺血性脑血管病(脑梗死)约占80%。临床研究及病理证实,脑梗死主要分为大动脉粥样硬化性脑梗死(ATCI)、心源性栓塞性脑梗死(CCI)、小动脉闭塞性脑梗死(LCI)、其他明确病因和不明原因等5大类。ATCI的病变基础就是动脉粥样硬化,具有高发病率、高致残率、高死亡率特点。因此,早期发现动脉硬化病变,及时进行有效的一、二级预防意义重大。尽管动脉造影、64排CT动脉成像等方法可以进行动脉病变检查,但因其有创、价格高、少数可有较严重并发症等原因不宜作为常规的早期检查方法。外周动脉粥样硬化程度在一定程度上可反映动脉粥样硬化及其严重程度,因此,对外周动脉管壁的形态及弹性功能的检测有助于预测动脉病变。近年来,病理学证实炎症过程贯穿于动脉粥样硬化的形成、起始及发展全过程。ATCI发生的主要机制是炎症活性诱导的易损斑块破裂诱发的急性血栓形成。易损斑块的炎性标记物越来越多地应用于ATCI病情的综合评价,常用的有hs-CRP、粘附分子(ICAM-1、VCAM-1)等。血管内皮是一种动力器官,通过各种机制抑制血液凝固和白细胞粘附,保持血液的流动性。单核细胞吞噬泡沫细胞,粘附在活化的内皮上,继而侵入内皮下层,这是形成动脉粥样硬化的关键启动步骤,这种粘附作用由ICAM-1、VCAM-1等介导。研究显示,氟伐他汀除能显著降低高密度胆固醇,还能够稳定动脉硬化斑块。目的本课题研究氟伐他汀对炎性易损斑块的稳定作用;并研究氟伐他汀应用前后患者动脉管壁及弹性变化,进一步验证氟伐他汀对ATCI的治疗作用。同时,利用高频超声对氟伐他汀干预的ATCI患者血管内皮功能及动脉斑块进行深入研究,来阐明超声在评价药物对血管功能中发挥着重要作用。方法将动脉粥样硬化性脑梗死组(ATCI)患者分为给予氟伐他汀(40mg qd po)治疗组和未给予氟伐他汀治疗组;每组34例,并与30例正常对照组进行比较。所有患者于入院次日及3个月后两次进行下述指标检测:①颈动脉超声、眼动脉超声(稳定和易损斑块数量、斑块指数、动脉内膜-中膜厚度IMT、收缩峰值速度PSV、舒张末速度EDV、阻力指数RI及搏动指数PI);②血脂(总胆固醇TC、甘油三酯TG、低密度脂蛋白胆固醇LDL-c、高密度脂蛋白胆固醇HDL-c);③可溶性细胞间黏附因子-1(sICAM-1)、可溶性血管细胞粘附因子-1(sVCAM-1)含量及mRNA和蛋白表达;④头颅CT/MRI;⑤神经功能缺损评分(NDS)。正常对照组也进行除了NDS以外的相同指标检测。所有患者在住院期间,均进行一般状况评估(血压、血糖),均给予改善循环、营养神经等治疗。结果1.颈动脉斑块比较:①两组ATCI患者在治疗前颈动脉斑块总数、稳定斑块或易损斑块数量差异无统计学意义(P＞0.05);经过治疗3个月,颈动脉斑块总数明显减少,稳定斑块有所增多,易损斑块明显减少,两组ATCI比较,差异有统计学意义(P＜0.01)。②两组ATCI间治疗前斑块指数和IMT比较,差异也无统计学意义(P＞0.05);经过治疗3个月,两组ATCI中斑块指数和IMT比较,差异也有统计学意义(P＜0.01)。2.颈动脉和眼动脉超声检测的血流动力学参数变化:两组ATCI患者在治疗前PSV、EDV、RI、PI等指标差异无统计学意义(P＞0.05);治疗3个月后,PSV、EDV增快,RI、PI下降,与治疗前相比较,氟伐他汀组改变更加显著(P＜0.01或P＜0.05),ATCI两组间上述各指标差异有统计学意义(P＜0.01)。3.血脂分析:两组ATCI患者治疗前TC、TG、LDL-c、HDL-c比较,差异无统计学意义(P＞0.05);经过治疗3个月,TC、TG、LDL-c浓度下降,HDL-c浓度升高,氟伐他汀组改变更显著,与常规治疗组相比较,差异有统计学意义(P＜0.01)。4.sICAM-1、sVCAM-1含量及mRNA和蛋白表达:两组ATCI患者治疗前sICAM-1、sVCAM-1含量及mRNA和蛋白表达比较,差异无统计学意义(P＞0.05);经过氟伐他汀治疗3个月,这两种粘附分子含量及mRNA和蛋白表达均有所下降,与常规治疗组相比较,差异有统计学意义(P＜0.01)。大、中、小病灶ATCI患者之间sICAM-1、sVCAM-1含量有差异(P＜0.01)。5.药物疗效的判定:两组ATCI患者在治疗前NDS无显著性差异(P＞0.05);经治疗3各月后,两组患者NDS均明显降低,与治疗前比较有统计学意义(P＜0.01),而氟伐他汀组降低的更明显,两组治疗后比较有统计学意义(P＜0.01)。6.药物不良反应的判定:所有患者在观察期间血、尿常规、肝肾功能、济钙孜捶⑸飨员浠?P＞0.05);也未见药物过敏、消化道反应、造血系统损害等不良反应及横纹肌溶解症的发生。结论氟伐他汀通过稳定斑块、改善动脉硬化血管的顺应性及弹性、降低LDL-c浓度、保护血管内皮功能等机制在ATCI的治疗中起着积极作用。颈动脉和眼动脉超声检测在评价药物对血管功能及在诊断ATCI中均发挥着重要作用。更多还原

【Abstract】 BackgroundsCerebral vascular diseases have been listed as one of ten most common diseases by World Health Organization (WHO) in the 21st century. In China, the prevalence of cerebrovascular disease ranks No. 3, in which ischemic cerebrovascular disease (cerebral infarction) accounts for about 80%. According to clinical and pathological examination, cerebral infarctions were divided into five categories including atherosclerotic cerebral infarction (ATCI), cardiogenic cerebral infarction (CCI), lacunar cerebral infarction (LCI), other determined etiologies and unknown reasons of cerebral infarction. Pathological basis of ATCI, which is characterized by high morbidity, high disability and high mortality, is atherosclerosis. Therefore, it’s very important to early detect atherosclerotic lesions, and timely and effectively prevent it in the first and second level.Although angiography, 64-slice CT scan has been used to detect arterial diseases, those methods are not routine ones because of invasive, expensive and some severe complications. Peripheral arterial atherosclerosis can reflect the atherosclerosis and its severity to some extent, therefore, vessel wall morphology and elasticity of peripheral arteries can predict arterial diseases.In recent years, pathology has confirmed inflammation run through the formation and development of the atherosclerosis. The main mechanism of ATCI is acute thrombosis induced by vulnerable plaque rupture which is caused by inflammation. Inflammatory markers from vulnerable plaque including hs-CRP, adhesion molecules (ICAM-1, VCAM-1) etc. have been used to evaluate ATCI.Vascular endothelial, a dynamic organ, can inhibit blood coagulation and leukocyte adhesion to maintain blood flow through various mechanisms. The key steps in the formation of atherosclerosis include monocytes engulfing foam cells, adhering to the activated endothelium and invading subendothelial layer, which of the process was mediated by ICAM-1, VCAM-1.Studies have shown that fluvastatin significantly reduce level of high-density cholesterol and stabilize the atherosclerotic plaque.ObjectivesTo determine the effect of fluvastatin on stabilizing inflammatory vulnerable plaques through inhibiting ICAM-1, VCAM-1 before and after having been treated by fluvastatin in the patients with ATCI. Meanwhile, endothelial function and arterial plaque were studied by high frequency ultrasound in the patients with ATCI before and after having been treated by fluvastatin to clarify high-frequency ultrasound in evaluating on carotid and ophthalmic artery plaques from the patients with ATCI intervened by fluvastatin.MethodsSixty-eight patients with ATCI were divided into two groups, conventional treatment group and fluvastatin treatment group, and 30 healthy men were chosen as controls.The following indexes were detected twice in all patients when they were 2nd day in the hospital and after 3 months.①Carotid artery ultrasound, ophthalmic artery ultrasound (the number of stable and vulnerable plaque; plaque index; arterial intima - media thickness, IMT; systolic peak velocity, PSV; end diastolic velocity, EDV; resistance index, RI and pulsatility index, PI)②Lipids (total cholesterol, TC; triglyceride, TG; low density lipoprotein cholesterol, LDL-c; high-density lipoprotein cholesterol, HDL-c)③Content, mRNA and protein expression of soluble intercellular adhesion molecule -1 (sICAM-1), soluble vascular cell adhesion molecule -1 (sVCAM-1);④Head CT / MRI;⑤Neurological deficit score (NDS). In addition, the normal control group were also detected the same indexes except for NDS. General conditions (blood pressure, blood sugar) were assessed in all of patients with ATCI when they were in the hospital, and some of drugs improving circulation, nervous protection were given in all of patients with ATCI.Results1. Comparison of carotid artery plaque:①Number of total, stable and unstable carotid artery plaques were no difference between two groups of ATCI before treatment (P>0.05). Number of total and unstable carotid artery plaques decreased, number of stable plaques increased, there were significant differences in above index between two groups of ATCI after 3 month treatment (P<0.01).②Plaque index and IMT were no difference between two groups of ATCI before treatment (P> 0.05). There were significant differences in plaque and IMT between two groups of ATCI after 3 month treatment (P<0.01).2. Hemodynamic parameters in carotid artery and ophthalmic artery by ultrasonic exam: There were no significant difference in PSV, EDV, RI and PI between two groups of ATCI before treatment (P>0.05). But PSV and EDV increased, RI and PI decreased in the patients with ATCI after treatment, especially in the patients intervened by fluvastatin, there were significant differences in above index between two groups of ATCI (P<0.01).3. Lipids: There were no significant difference in TC, TG, HDL-c and LDL-c between two groups of ATCI before treatment (P>0.05). Concentrations of TC, TG and LDL-c decreased, and concentration of HDL-c increased in the patients with ATCI after treatment, especially in the patients intervened by fluvastatin, there were significant differences in above index between two groups of ATCI (P<0.0l).4. Contents, mRNA and protein expressions of sICAM-1 and sVCAM-1: There were no significant difference in all of indexes between two groups of ATCI before treatment (P>0.05). Contents, mRNA and protein expressions of sICAM-1 and sVCAM-1 decreased after treatment, especially in the patients intervened by fluvastatin, there were significant differences between two groups of ATCI (P<0.01). Among large, medium and small lesions in the patients with ATCI treated by fluvastatin, sICAM-1 and sVCAM-1 levels were significantly different (P<0.01).5. Drug efficacy: There were no significant difference in NDS between two groups of ATCI before treatment (P>0.05). NDS decreased after treatment, especially in the patients intervened by fluvastatin, there were significant differences between two groups of ATCI (P<0.01).6. Drug adverse reactions: All the patients in the observation period had no significant changes in blood, urine, liver and kidney function and muscle enzymes (P > 0.05); no patient has drug allergy, gastrointestinal reactions, coagulation mechanism damage and other adverse reactions, neither has rhabdomyolysis.ConclusionsFluvastatin plays an active role in the treatment of ATCI through stabilizing the plaque, improving compliance and flexibility of atherosclerotic blood vessels, reducing concentration of LDL-c and protecting function of vascular endothelial. Carotid artery and ophthalmic artery ultrasonography play an important role in both the evaluation of drugs on vascular function and the diagnosis of ATCI.更多还原