颈部动脉夹层的诊疗探索以及发病机制的初步探究

发布时间：2018-03-30 11:29

本文选题：头颈部动脉夹层　切入点：治疗方式　出处：《第三军医大学》2017年硕士论文

【摘要】：背景:颈动脉夹层是中青年患者脑卒中的重要因素之一,在小于45岁的青年卒中患者中颈动脉夹层患者的则占了10%~25%。如此高的发病率不仅给个人带来了极大的伤害,同时给社会和家庭也带来了沉重的负担。由于国内外缺乏颈动脉夹层流行病学、诊断与治疗方面的大样本研究,且临床医师重视不够,易导致漏诊或误诊。目前关于颈部动脉夹层早期卒中复发的风险评估还有许多不同意见,有的学者认为颈部动脉夹层早期卒中复发风险较高不容忽视,可也有学者认为颈部动脉夹层有自愈倾向。但无论如何,抗血栓形成治疗也是必不可少的,尤其是在发病早期。现在抗血栓形成治疗主要有两种方式,一种是3~6个月的抗凝治疗,一种是抗血小板治疗。当前许多医院倾向于使用抗凝治疗,但是相比较与抗血小板治疗而言,抗凝治疗的脑出血风险明显增加,所以两者的疗效与安全性仍是研究的重点。随着血管内治疗的发展,该项治疗也用于颈部动脉夹层的治疗,但仍缺乏大样本量研究证实其安全性与有效性。近年来他汀类药物广泛应用于脑卒中的治疗,其非降脂作用是现在医学关注的重点,是否他汀药物的抗炎作用在颈部动脉夹层的治疗中起到了一定疗效,也是我们需要探明的问题。目前我们对于颈部动脉夹层的发病机制知之甚少,认为其可能与非特异性或遗传性动脉壁结构和/或功能异常、血流动力学变化、血管壁炎症、头颈部运动致血管壁压力增加、近期感染、季节因素以及某些常见脑血管病危险因素如高血压、高血脂、男性、吸烟等因素有关。所以急需建立大动物的颈部动脉夹层模型,探明其发病机制,为临床的治疗与预防指明方向。第一部分头颈部动脉夹层患者治疗的回顾性分析目的:探讨不同治疗方式以及不同药物对于头颈部动脉夹层的患者预后的影响。方法:回顾性分析我院从2003年3月至2014年7月收治的94例动头颈部脉夹层病人的临床资料,对患者的性别、发病年龄、临床表现、实验室检查、夹层发生部位、药物治疗与血管内治疗、抗凝治疗与抗栓治疗、他汀类药物的治疗、死亡率、卒中再发率分别进行了3个月的短期随访与3年的长期随访研究。结果:3月总随访88人,随访率93.6%;3年随访81人,随访率86.2%。所有患者至少药物治疗3个月,症状轻重以入院NIHSS评分判断,3月后mRS≤2分认为预后良好。3个月内死亡2人,3年内死亡5人,总死亡率7.4%。3个月内再发脑卒中2人,3年内再发脑卒中7人,总脑卒中再发率9.6%。共有22例行血管内支架植入术,用卡方检验分析不同治疗方式的近远期效果,3月内血管内支架植入治疗组效果优于药物治疗组(χ2=3.058,P=0.039);药物治疗中,使用他汀类药物治疗组3个月时脑卒中复发率低于未使用他汀类药物治疗组(χ2=2.250,P=0.041)。卡方检验分析3个月内抗凝、单抗、双抗、抗凝合联合单抗4种药物治疗方式对于脑卒中再发率之间存在显著差异(χ2=13.795,P=0.003),进一步卡方切割后两两比较分析,单抗与抗凝联合单抗治疗组之间有显著差异(χ2=8.308,P=0.004);双抗与抗凝联合单抗治疗组之间有显著差异(χ2=8.320,P=0.004)。结论:男性患者以TIA为首发症状的居多,而女性患者以头晕症状多见;头颈部外伤以及按摩会诱发夹层,有偏头痛病史的患者,可能与夹层的发生有关;椎动脉夹层女性多发,而颅内动脉夹层多见于男性;颈动脉夹层更多发生在年龄较大的人群;头颈部疼痛症状更多见于椎动脉夹层;颅内动脉夹层导致的神经系统症状更重;血管内支架植入治疗近期疗效优于药物治疗;他汀类药物的使用可降低患者3月内的脑卒中再发率;抗凝治疗与抗血小板聚集治疗效果无明显差异;抗凝联合单抗治疗增加短期内脑卒中再发率;不同的治疗方式以及用药方案,对于远期死亡率以及脑卒中再发率无明显影响;起病症状轻重对近远期死亡率、脑卒中再发率无明显影响。第二部分猪颈动脉夹层模型的建立以及发病机制的初步研究目的:建立猪颈动脉夹层模型,初步探讨炎性反应在颈部动脉夹层中的作用。方法:采用显微镜直视下分离猪颈动脉内膜结合球囊扩张的方法,建立猪颈动脉夹层的模型,并用影像学方法以及病理标本验证模型是否成功。再分别取模型动物急性期(72小时)和慢性期(6个月)夹层部位的血管标本,以及假手术组相应部位的血管标本,进行i TRAQ定量蛋白质组学检测。结果:通过高分辨率磁共振、血管超声以及DSA验证猪颈动脉夹层模型建成,病理HE染色可见血管真假腔形成,可见免疫荧光染色的CD31标记的受损的内皮细胞;i TRAQ共检测出颈动脉夹层中的蛋白质58种,其中参与免疫反应的蛋白质达到37种,其次是参与血液凝固9种,调节转录4种,氧化应激3种,生长因子3种以及脂质代谢2种。结论:显微镜直视下分离内膜结合球囊扩张能成功建立夹层动物模型,从影像学、病理学方面可模拟颈动脉夹层发生以及发展的情况。i TRAQ检测出参与颈动脉夹层的蛋白质58种,其中免疫反应的蛋白质占到了64%,侧面证明炎性反应在颈动脉夹层中起到了重要作用。
[Abstract]:Background: cervical artery dissection is one of the important factors in young patients with stroke, in young stroke patients less than 45 years of age in patients with carotid artery dissection is 10%~25%. for this high incidence of not only to the individual has brought great harm to the society and family, but also brought a heavy burden due to lack. Cervical artery dissection, epidemiology, diagnosis and treatment of large sample, and the clinician enough attention, easily lead to misdiagnosis. The risk assessment on the cervical artery dissection of early recurrent stroke, there are many different views, some scholars think that the cervical artery dissection early high risk of recurrent stroke can not be ignored, but some scholars believe that there are cervical artery dissection autotherapy. But in any case, antithrombotic therapy is also essential, especially in the early stage of disease. Now the antithrombotic therapy to In two ways, one is the anticoagulant treatment for 3~6 months, is a kind of antiplatelet therapy. Currently many hospitals tend to use anticoagulation therapy, but compared with antiplatelet therapy, anticoagulant therapy significantly increased risk of cerebral hemorrhage, the efficacy and safety of the two is still the focus of the study. With the development of endovascular treatment, the treatment is also used in the treatment of cervical artery dissection, but still lack of large sample studies confirmed the safety and efficacy of treatment in recent years. Statins are widely used in stroke, the non lipid-lowering effect is now focusing on medical attention, whether the anti-inflammatory effects of statins in the treatment of cervical artery dissection plays a certain effect, but also we need to study the problem. We know little about the pathogenesis of cervical artery dissection at present, it may with nonspecific or hereditary arterial wall The structure and / or functional abnormalities, hemodynamic changes, vascular inflammation, head and neck movement caused by vascular wall pressure increase, recent infection, seasonal factors and some common risk factors of cerebrovascular disease such as hypertension, hyperlipidemia, male, smoking and other factors. So there is an urgent need to build up a large animal model of cervical artery dissection, ascertain the the pathogenesis, clinical treatment and prevention direction. The first treatment were divided into cervical artery dissection were retrospectively analyzed to explore the effect of different treatment methods and different drugs for head and neck dissection in patients prognosis. Methods: retrospective analysis of our hospital from March 2003 to July 2014 were 94 cases of head and neck vein patients with dissection of the clinical data of patients with gender, age of onset, clinical manifestations, laboratory examination, dissection positions, drug treatment and blood vessels within the anticoagulation and antithrombotic therapy. The treatment, treatment of statins, mortality, stroke recurrence rate were 3 months and 3 years of short-term follow-up of long-term follow-up study. Results: in March 88 follow-up, follow-up rate was 93.6%; 3 years of follow-up of 81 people, the follow-up rate was 86.2%. in all patients at least 3 months of treatment, the symptoms in the admission NIHSS score to determine, after March mRS is less than or equal to 2 points that killed 2 people and a good prognosis within.3 months, 5 people died in 3 years, the total mortality rate within 7.4%.3 months of recurrent stroke in 2, 3 years of recurrent stroke in 7 people, the total stroke recurrence rate of 9.6%. a total of 22 cases of vascular stent implantation, short term effect of different treatment methods by chi square analysis, in March the endovascular stent treatment group is better than the drug treatment group (2=3.058, P=0.039); drug therapy, the use of statins in treatment group at 3 months, the recurrence rate of cerebral ischemic stroke without the use of statin treatment group was lower than that of (x 2=2.2 50, P=0.041). The chi square test within 3 months of anticoagulation, monoclonal antibody, double antibody, monoclonal antibody anticoagulant combination of 4 drugs in the treatment of the stroke recurrence rate had significant difference between (x 2=13.795, P=0.003), chi square after cutting 22 further comparative analysis, combined with anticoagulant monoclonal antibody mAb has significant difference between treatment groups (2=8.308, P=0.004); double antibody and monoclonal antibody therapy combined with anticoagulation between groups were significantly different (2=8.320, P=0.004). Conclusion: male patients with TIA were the first symptoms, and female patients with dizziness symptoms; head and neck injury and massage will induce dissection, with a history of migraine patients may be related to the occurrence of dissection; vertebral artery dissection female with multiple intracranial artery dissection is more common in men; carotid artery dissection occurred more in older populations; head and neck pain in vertebral artery dissection; intracranial artery dissection result The nervous system symptoms heavier; endovascular stent implantation in the treatment of curative effect is better than that of drug treatment; use of statins can reduce stroke recurrence rate in March; the anticoagulation and antiplatelet treatment had no significant difference; monoclonal antibody in the treatment of anticoagulation combined short-term increase in stroke recurrence rate; different treatment and a regimen for long-term mortality and stroke recurrence rate had no significant effect on the onset of symptoms; long-term mortality, stroke recurrence rate had no obvious effect. Objective to investigate second porcine carotid artery dissection model establishment and pathogenesis of porcine carotid artery dissection: to establish a model to investigate the role of inflammatory reaction in cervical artery dissection. Methods: using the microscope in isolated swine carotid media combined with balloon dilatation, the model of porcine carotid artery dissection, and use. The imaging methods and pathological specimens to validate the model of success. Then take the animal model of acute (72 h) and chronic period (6 months) the interlayer part of vascular specimens, and the sham operation group and vascular specimens of I TRAQ quantitative proteomics detection. Results: by high resolution magnetic resonance, built vascular ultrasound and DSA verification of porcine carotid artery dissection model, pathological HE staining of vascular and false lumen formation, impaired endothelial cell marker CD31 visible immunofluorescence staining; I TRAQ detected a total of 58 proteins of carotid artery dissection, the protein involved in the immune response to 37, followed by 9 in blood coagulation 4, 3 kinds of transcriptional regulation, oxidative stress, lipid metabolism and growth factor 3 2. Conclusion: microscope intimal separation combined with balloon dilation can be successfully established the animal model of sandwich, from imaging, pathology It can simulate the occurrence and development of carotid artery dissection..i TRAQ detected 58 kinds of proteins involved in carotid artery dissection, of which 64% of the immunoreactive protein accounted for about 2%. Side effects showed that inflammatory response played an important role in carotid artery dissection.

【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R743.3

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