本文選題：腦動(dòng)靜脈畸形 + 酪氨酸激酶��； 參考：《河北醫(yī)科大學(xué)》2014年碩士論文

【摘要】：目的：腦動(dòng)靜脈畸形是一種自發(fā)性血管性疾病，是由于顱內(nèi)局部血管發(fā)育異常，進(jìn)而形成迂曲、粗細(xì)不等的畸形血管團(tuán)。研究發(fā)現(xiàn)，酪氨酸激酶家族的EphrinB2配體/EphB4受體雙向信號(hào)傳導(dǎo)通路可以促進(jìn)血管發(fā)育，在血管內(nèi)皮細(xì)胞增殖、遷移、分化等形成血管的過程中發(fā)揮重要作用，進(jìn)而調(diào)控動(dòng)靜脈畸形異常血管團(tuán)的形成與發(fā)展。同時(shí)，長期處于高血流動(dòng)力學(xué)狀態(tài)的腦動(dòng)靜脈畸形異常血管團(tuán)，會(huì)導(dǎo)致周圍組織存在相對(duì)的低氧環(huán)境，刺激組織分泌相應(yīng)生長因子，促進(jìn)血管的生成和重塑。EphrinB2配體的表達(dá)和血流動(dòng)力學(xué)狀態(tài)的改變都會(huì)調(diào)控血管的發(fā)育，進(jìn)而導(dǎo)致腦動(dòng)靜脈畸形異常血管團(tuán)的形成。二者之間相互作用的機(jī)制尚不清楚。通過研究不同血流動(dòng)力學(xué)狀態(tài)下腦動(dòng)靜脈畸形異常血管團(tuán)內(nèi)EphrinB2配體的表達(dá)水平，探討EphrinB2配體表達(dá)與動(dòng)靜脈畸形異常血管團(tuán)內(nèi)血流動(dòng)力學(xué)的關(guān)聯(lián)性，探討不同血流動(dòng)力學(xué)狀態(tài)下畸形血管團(tuán)內(nèi)微環(huán)境的改變對(duì)EphrinB2配體表達(dá)水平及其調(diào)控血管發(fā)育的影響，為臨床診治腦動(dòng)靜脈畸形提供理論基礎(chǔ)和實(shí)驗(yàn)依據(jù)。 方法：選取經(jīng)數(shù)字減影血管造影術(shù)（DSA）確診的腦動(dòng)靜脈畸形患者48例，通過每幀DSA圖像上注入造影劑與攝片的時(shí)間間隔，計(jì)算每位腦動(dòng)靜脈畸形患者畸形血管團(tuán)的供血?jiǎng)用}A與引流靜脈V出現(xiàn)的時(shí)隔間間隔（A-V），將患者按腦動(dòng)靜脈畸形異常血管團(tuán)的血流動(dòng)力分為兩組：高排低阻型（A-V＜2秒），，20例；低排高阻型（A-V＞2秒），28例。分別對(duì)每位患者術(shù)中獲取的腦動(dòng)靜脈畸形異常血管團(tuán)石蠟包埋切片標(biāo)本進(jìn)行免疫組織化學(xué)染色，以EphrinB2配體的表達(dá)為陽性結(jié)果，將染色結(jié)果分為強(qiáng)染色組和弱染色組兩組，然后通過SPSS16.0進(jìn)行EphrinB2配體表達(dá)水平與血流動(dòng)力學(xué)的關(guān)聯(lián)性分析。 結(jié)果：EphrinB2配體表達(dá)于動(dòng)脈血管呢皮細(xì)胞上，48例腦動(dòng)靜脈畸形患者中弱染色組26例，強(qiáng)染色組22例。結(jié)合腦動(dòng)靜脈畸形異常血管團(tuán)血流動(dòng)力學(xué)，48例患者可分為四組：高排低阻型、強(qiáng)染色阻患者18例，高排低阻型、弱染色組患者2例；低排高阻型、強(qiáng)染色組患者4例，低排高阻型、弱染色組患者24例。通過SPSS16.0進(jìn)行關(guān)聯(lián)性分析，結(jié)果P＜0.01，認(rèn)為EphrinB2配體的表達(dá)水平與腦動(dòng)靜脈畸形異常血管團(tuán)的血流動(dòng)力學(xué)具有關(guān)聯(lián)性，其關(guān)聯(lián)系數(shù)為C=0.6。 討論：近年來的實(shí)驗(yàn)研究發(fā)現(xiàn)：EphrinB2配體/ephB4受體雙向信號(hào)傳導(dǎo)通路在腦動(dòng)靜脈畸形異常血管團(tuán)的生成過程中發(fā)揮重要作用。動(dòng)物實(shí)驗(yàn)發(fā)現(xiàn)EphrinB2配體可以促進(jìn)血管發(fā)育，缺失EphrinB2配體基因的小鼠在胚胎期因血管發(fā)育缺陷導(dǎo)致死亡。腫瘤組織的新生血管內(nèi)也發(fā)現(xiàn)EphrinB2配體的表達(dá)水平升高。血管內(nèi)皮細(xì)胞培養(yǎng)實(shí)驗(yàn)表明，在培養(yǎng)基內(nèi)加入EphrinB2-Fc，會(huì)促進(jìn)血管內(nèi)皮細(xì)胞增殖，促進(jìn)微血管的生成。 流行病學(xué)調(diào)查發(fā)現(xiàn)：經(jīng)多普勒超聲（TCD）檢測(cè)，腦動(dòng)靜脈畸形異常血管團(tuán)供血?jiǎng)用}的阻力指數(shù)（RI）小于正常顱內(nèi)動(dòng)脈的阻力指數(shù)，即腦動(dòng)靜脈畸形異常血管團(tuán)的血流動(dòng)力學(xué)狀態(tài)較正常升高，畸形血管團(tuán)長期處于高血流動(dòng)力狀態(tài)。 目前，診斷腦動(dòng)靜脈畸形的影像學(xué)“金標(biāo)準(zhǔn)”是數(shù)字減影血管造影術(shù)（DSA），不僅可以發(fā)現(xiàn)腦動(dòng)靜脈畸形異常血管團(tuán)的大小、形狀及其與鄰近血管組織的關(guān)系，還可以明確畸形血管團(tuán)的供血?jiǎng)用}（A）和引流靜脈（V）。同時(shí)，通過每幀圖像的顯像時(shí)間，可以計(jì)算血液通過畸形血管團(tuán)的時(shí)間間隔（A-V），并以此表示腦動(dòng)靜脈畸形異常血管團(tuán)的血流動(dòng)力學(xué)狀態(tài)（時(shí)間間隔A-V越小，腦動(dòng)靜脈畸形異常血管團(tuán)的血流動(dòng)力越大）。 本實(shí)驗(yàn)結(jié)果發(fā)現(xiàn)EphrinB2配體的表達(dá)與腦動(dòng)靜脈畸形異常血管團(tuán)的血流動(dòng)力學(xué)狀態(tài)具有關(guān)聯(lián)性，且關(guān)聯(lián)系數(shù)為0.6，說明血流動(dòng)力學(xué)狀態(tài)的改變和EphrinB2配體的表達(dá)通過二者間的相互作用共同調(diào)控腦動(dòng)靜脈畸形異常血管團(tuán)�；窝軋F(tuán)的高血流動(dòng)力學(xué)狀態(tài)會(huì)刺激EphrinB2配體的表達(dá)，進(jìn)而調(diào)控血管內(nèi)皮細(xì)胞的增殖、遷移、分化，促進(jìn)腦動(dòng)靜脈畸形的發(fā)育。反之，降低腦動(dòng)靜脈畸形異常血管團(tuán)內(nèi)血流動(dòng)力學(xué)狀態(tài)，將減少EphrinB2配體的表達(dá)，抑制腦動(dòng)靜脈畸形的發(fā)展。進(jìn)一步研究血流動(dòng)力學(xué)狀態(tài)和EphrinB2配體之間相互作用的機(jī)制，將為臨床上通過改變畸形血管團(tuán)的血流動(dòng)力學(xué)狀態(tài)防治腦動(dòng)靜脈畸形提供理論基礎(chǔ)和實(shí)驗(yàn)依據(jù)。
[Abstract]:Objective : To investigate the relationship between the expression of EphrinB2 ligand and EphB4 receptor in vascular endothelial cells and to regulate the formation and development of vascular endothelial cells .

Methods : 48 cases of cerebral arteriovenous malformation diagnosed by digital subtraction angiography ( DSA ) were selected , and the time interval between the contrast agent and the image was injected on the DSA image of each frame . The time interval between the blood supply artery A and the drainage vein V of each cerebral arteriovenous malformation was calculated . The hemodynamic parameters of the abnormal blood vessels of the cerebral arteriovenous malformations were divided into two groups : high - row low - resistance type ( A - V < 2 seconds ) and 20 cases ;
Low - rank high - resistance ( A - V & gt ; 2 s ) and 28 cases were used for immunohistochemical staining of paraffin - embedded sections of cerebral arteriovenous malformations acquired in each patient . The results were as follows : the expression of EphrinB2 ligand was positive , and the results were divided into two groups : strong staining group and weak staining group . Then , the relationship between the expression level of EphrinB2 ligand and hemodynamics was analyzed by SPSS 16.0 .

Results : EphrinB2 ligand was expressed in arterial blood vessel . In 48 cases of cerebral arteriovenous malformation , 26 cases were weak staining group and 22 cases with strong staining group .
The relationship between the expression level of EphrinB2 ligand and the hemodynamics of abnormal vascular mass of cerebral arteriovenous malformations was determined by SPSS 16.0 , and the correlation coefficient was C = 0.6 .

In recent years , it has been found that EphrinB2 ligand / EphB4 receptor two - way signaling pathway plays an important role in the formation of abnormal blood vessels in cerebral arteriovenous malformations . In animal experiments , EphrinB2 ligand can promote the development of vascular endothelial cells . The expression level of EphrinB2 ligand is increased in the angiogenesis of tumor tissues . The experiment of endothelial cell culture shows that EphrinB2 - Fc is added to the culture medium , which promotes the proliferation of vascular endothelial cells and promotes the formation of microvessels .

Epidemiological investigation showed that the resistance index ( RI ) of abnormal vascular mass of cerebral arteriovenous malformation was lower than that of normal intracranial artery by Doppler ultrasound ( TCD ) .

At present , the diagnosis of cerebral arteriovenous malformation is a digital subtraction angiography ( DSA ) , which not only can find the size , shape and relationship with adjacent vascular tissue , but also can identify the blood supply artery ( A ) and the drainage vein ( V ) of the abnormal vascular mass . At the same time , the time interval ( A - V ) of the abnormal vascular mass of the cerebral arteriovenous malformation can be calculated by the imaging time of each frame image , and the blood flow dynamics state of the abnormal blood vessel of the cerebral arteriovenous malformation ( the smaller the time interval A - V , the greater the blood flow power of the abnormal vascular mass of the cerebral arteriovenous malformation ) can be calculated .

The results show that EphrinB2 ligand expression is related to the hemodynamic status of abnormal vascular mass of cerebral arteriovenous malformations , and the correlation coefficient is 0.6 . It is suggested that the change of blood flow dynamics and the expression of EphrinB2 ligand can regulate the development of cerebral arteriovenous malformations .
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R743.4

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