本文選題：頭頸部動脈夾層　切入點：治療方式　出處：《第三軍醫(yī)大學(xué)》2017年碩士論文

【摘要】：背景:頸動脈夾層是中青年患者腦卒中的重要因素之一,在小于45歲的青年卒中患者中頸動脈夾層患者的則占了10%~25%。如此高的發(fā)病率不僅給個人帶來了極大的傷害,同時給社會和家庭也帶來了沉重的負(fù)擔(dān)。由于國內(nèi)外缺乏頸動脈夾層流行病學(xué)、診斷與治療方面的大樣本研究,且臨床醫(yī)師重視不夠,易導(dǎo)致漏診或誤診。目前關(guān)于頸部動脈夾層早期卒中復(fù)發(fā)的風(fēng)險評估還有許多不同意見,有的學(xué)者認(rèn)為頸部動脈夾層早期卒中復(fù)發(fā)風(fēng)險較高不容忽視,可也有學(xué)者認(rèn)為頸部動脈夾層有自愈傾向。但無論如何,抗血栓形成治療也是必不可少的,尤其是在發(fā)病早期。現(xiàn)在抗血栓形成治療主要有兩種方式,一種是3~6個月的抗凝治療,一種是抗血小板治療。當(dāng)前許多醫(yī)院傾向于使用抗凝治療,但是相比較與抗血小板治療而言,抗凝治療的腦出血風(fēng)險明顯增加,所以兩者的療效與安全性仍是研究的重點。隨著血管內(nèi)治療的發(fā)展,該項治療也用于頸部動脈夾層的治療,但仍缺乏大樣本量研究證實其安全性與有效性。近年來他汀類藥物廣泛應(yīng)用于腦卒中的治療,其非降脂作用是現(xiàn)在醫(yī)學(xué)關(guān)注的重點,是否他汀藥物的抗炎作用在頸部動脈夾層的治療中起到了一定療效,也是我們需要探明的問題。目前我們對于頸部動脈夾層的發(fā)病機(jī)制知之甚少,認(rèn)為其可能與非特異性或遺傳性動脈壁結(jié)構(gòu)和/或功能異常、血流動力學(xué)變化、血管壁炎癥、頭頸部運(yùn)動致血管壁壓力增加、近期感染、季節(jié)因素以及某些常見腦血管病危險因素如高血壓、高血脂、男性、吸煙等因素有關(guān)。所以急需建立大動物的頸部動脈夾層模型,探明其發(fā)病機(jī)制,為臨床的治療與預(yù)防指明方向。第一部分頭頸部動脈夾層患者治療的回顧性分析目的:探討不同治療方式以及不同藥物對于頭頸部動脈夾層的患者預(yù)后的影響。方法:回顧性分析我院從2003年3月至2014年7月收治的94例動頭頸部脈夾層病人的臨床資料,對患者的性別、發(fā)病年齡、臨床表現(xiàn)、實驗室檢查、夾層發(fā)生部位、藥物治療與血管內(nèi)治療、抗凝治療與抗栓治療、他汀類藥物的治療、死亡率、卒中再發(fā)率分別進(jìn)行了3個月的短期隨訪與3年的長期隨訪研究。結(jié)果:3月總隨訪88人,隨訪率93.6%;3年隨訪81人,隨訪率86.2%。所有患者至少藥物治療3個月,癥狀輕重以入院NIHSS評分判斷,3月后mRS≤2分認(rèn)為預(yù)后良好。3個月內(nèi)死亡2人,3年內(nèi)死亡5人,總死亡率7.4%。3個月內(nèi)再發(fā)腦卒中2人,3年內(nèi)再發(fā)腦卒中7人,總腦卒中再發(fā)率9.6%。共有22例行血管內(nèi)支架植入術(shù),用卡方檢驗分析不同治療方式的近遠(yuǎn)期效果,3月內(nèi)血管內(nèi)支架植入治療組效果優(yōu)于藥物治療組(χ2=3.058,P=0.039);藥物治療中,使用他汀類藥物治療組3個月時腦卒中復(fù)發(fā)率低于未使用他汀類藥物治療組(χ2=2.250,P=0.041)�？ǚ綑z驗分析3個月內(nèi)抗凝、單抗、雙抗、抗凝合聯(lián)合單抗4種藥物治療方式對于腦卒中再發(fā)率之間存在顯著差異(χ2=13.795,P=0.003),進(jìn)一步卡方切割后兩兩比較分析,單抗與抗凝聯(lián)合單抗治療組之間有顯著差異(χ2=8.308,P=0.004);雙抗與抗凝聯(lián)合單抗治療組之間有顯著差異(χ2=8.320,P=0.004)。結(jié)論:男性患者以TIA為首發(fā)癥狀的居多,而女性患者以頭暈癥狀多見;頭頸部外傷以及按摩會誘發(fā)夾層,有偏頭痛病史的患者,可能與夾層的發(fā)生有關(guān);椎動脈夾層女性多發(fā),而顱內(nèi)動脈夾層多見于男性;頸動脈夾層更多發(fā)生在年齡較大的人群;頭頸部疼痛癥狀更多見于椎動脈夾層;顱內(nèi)動脈夾層導(dǎo)致的神經(jīng)系統(tǒng)癥狀更重;血管內(nèi)支架植入治療近期療效優(yōu)于藥物治療;他汀類藥物的使用可降低患者3月內(nèi)的腦卒中再發(fā)率;抗凝治療與抗血小板聚集治療效果無明顯差異;抗凝聯(lián)合單抗治療增加短期內(nèi)腦卒中再發(fā)率;不同的治療方式以及用藥方案,對于遠(yuǎn)期死亡率以及腦卒中再發(fā)率無明顯影響;起病癥狀輕重對近遠(yuǎn)期死亡率、腦卒中再發(fā)率無明顯影響。第二部分豬頸動脈夾層模型的建立以及發(fā)病機(jī)制的初步研究目的:建立豬頸動脈夾層模型,初步探討炎性反應(yīng)在頸部動脈夾層中的作用。方法:采用顯微鏡直視下分離豬頸動脈內(nèi)膜結(jié)合球囊擴(kuò)張的方法,建立豬頸動脈夾層的模型,并用影像學(xué)方法以及病理標(biāo)本驗證模型是否成功。再分別取模型動物急性期(72小時)和慢性期(6個月)夾層部位的血管標(biāo)本,以及假手術(shù)組相應(yīng)部位的血管標(biāo)本,進(jìn)行i TRAQ定量蛋白質(zhì)組學(xué)檢測。結(jié)果:通過高分辨率磁共振、血管超聲以及DSA驗證豬頸動脈夾層模型建成,病理HE染色可見血管真假腔形成,可見免疫熒光染色的CD31標(biāo)記的受損的內(nèi)皮細(xì)胞;i TRAQ共檢測出頸動脈夾層中的蛋白質(zhì)58種,其中參與免疫反應(yīng)的蛋白質(zhì)達(dá)到37種,其次是參與血液凝固9種,調(diào)節(jié)轉(zhuǎn)錄4種,氧化應(yīng)激3種,生長因子3種以及脂質(zhì)代謝2種。結(jié)論:顯微鏡直視下分離內(nèi)膜結(jié)合球囊擴(kuò)張能成功建立夾層動物模型,從影像學(xué)、病理學(xué)方面可模擬頸動脈夾層發(fā)生以及發(fā)展的情況。i TRAQ檢測出參與頸動脈夾層的蛋白質(zhì)58種,其中免疫反應(yīng)的蛋白質(zhì)占到了64%,側(cè)面證明炎性反應(yīng)在頸動脈夾層中起到了重要作用。
[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.

【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R743.3

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本文編號：1685727