酪氨酸家族配体EphrinB2与血流动力学的关联性分析

发布时间：2018-06-06 01:52

本文选题：脑动静脉畸形 + 酪氨酸激酶　；参考：《河北医科大学》2014年硕士论文

【摘要】：目的：脑动静脉畸形是一种自发性血管性疾病，是由于颅内局部血管发育异常，进而形成迂曲、粗细不等的畸形血管团。研究发现，酪氨酸激酶家族的EphrinB2配体/EphB4受体双向信号传导通路可以促进血管发育，在血管内皮细胞增殖、迁移、分化等形成血管的过程中发挥重要作用，进而调控动静脉畸形异常血管团的形成与发展。同时，长期处于高血流动力学状态的脑动静脉畸形异常血管团，会导致周围组织存在相对的低氧环境，刺激组织分泌相应生长因子，促进血管的生成和重塑。EphrinB2配体的表达和血流动力学状态的改变都会调控血管的发育，进而导致脑动静脉畸形异常血管团的形成。二者之间相互作用的机制尚不清楚。通过研究不同血流动力学状态下脑动静脉畸形异常血管团内EphrinB2配体的表达水平，探讨EphrinB2配体表达与动静脉畸形异常血管团内血流动力学的关联性，探讨不同血流动力学状态下畸形血管团内微环境的改变对EphrinB2配体表达水平及其调控血管发育的影响，为临床诊治脑动静脉畸形提供理论基础和实验依据。方法：选取经数字减影血管造影术（DSA）确诊的脑动静脉畸形患者48例，通过每帧DSA图像上注入造影剂与摄片的时间间隔，计算每位脑动静脉畸形患者畸形血管团的供血动脉A与引流静脉V出现的时隔间间隔（A-V），将患者按脑动静脉畸形异常血管团的血流动力分为两组：高排低阻型（A-V＜2秒），，20例；低排高阻型（A-V＞2秒），28例。分别对每位患者术中获取的脑动静脉畸形异常血管团石蜡包埋切片标本进行免疫组织化学染色，以EphrinB2配体的表达为阳性结果，将染色结果分为强染色组和弱染色组两组，然后通过SPSS16.0进行EphrinB2配体表达水平与血流动力学的关联性分析。结果：EphrinB2配体表达于动脉血管呢皮细胞上，48例脑动静脉畸形患者中弱染色组26例，强染色组22例。结合脑动静脉畸形异常血管团血流动力学，48例患者可分为四组：高排低阻型、强染色阻患者18例，高排低阻型、弱染色组患者2例；低排高阻型、强染色组患者4例，低排高阻型、弱染色组患者24例。通过SPSS16.0进行关联性分析，结果P＜0.01，认为EphrinB2配体的表达水平与脑动静脉畸形异常血管团的血流动力学具有关联性，其关联系数为C=0.6。讨论：近年来的实验研究发现：EphrinB2配体/ephB4受体双向信号传导通路在脑动静脉畸形异常血管团的生成过程中发挥重要作用。动物实验发现EphrinB2配体可以促进血管发育，缺失EphrinB2配体基因的小鼠在胚胎期因血管发育缺陷导致死亡。肿瘤组织的新生血管内也发现EphrinB2配体的表达水平升高。血管内皮细胞培养实验表明，在培养基内加入EphrinB2-Fc，会促进血管内皮细胞增殖，促进微血管的生成。流行病学调查发现：经多普勒超声（TCD）检测，脑动静脉畸形异常血管团供血动脉的阻力指数（RI）小于正常颅内动脉的阻力指数，即脑动静脉畸形异常血管团的血流动力学状态较正常升高，畸形血管团长期处于高血流动力状态。目前，诊断脑动静脉畸形的影像学“金标准”是数字减影血管造影术（DSA），不仅可以发现脑动静脉畸形异常血管团的大小、形状及其与邻近血管组织的关系，还可以明确畸形血管团的供血动脉（A）和引流静脉（V）。同时，通过每帧图像的显像时间，可以计算血液通过畸形血管团的时间间隔（A-V），并以此表示脑动静脉畸形异常血管团的血流动力学状态（时间间隔A-V越小，脑动静脉畸形异常血管团的血流动力越大）。本实验结果发现EphrinB2配体的表达与脑动静脉畸形异常血管团的血流动力学状态具有关联性，且关联系数为0.6，说明血流动力学状态的改变和EphrinB2配体的表达通过二者间的相互作用共同调控脑动静脉畸形异常血管团。畸形血管团的高血流动力学状态会刺激EphrinB2配体的表达，进而调控血管内皮细胞的增殖、迁移、分化，促进脑动静脉畸形的发育。反之，降低脑动静脉畸形异常血管团内血流动力学状态，将减少EphrinB2配体的表达，抑制脑动静脉畸形的发展。进一步研究血流动力学状态和EphrinB2配体之间相互作用的机制，将为临床上通过改变畸形血管团的血流动力学状态防治脑动静脉畸形提供理论基础和实验依据。
[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 .
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R743.4

【参考文献】