无水酒精在降低动静脉畸形栓塞治疗复发率中作用及机制的实验研究

Arteriovenous malformations (AVMs), mostly involve the oral and maxillofacial region, are harmful to the sufferred patients, as the physical and psychological issues are corncerned. Embolization is the prefrred therapy for these complicated diseases. However, the recurrence after the embolotherapy which use the glue or(and) PVA as the embolic agents are common in the long-term follow-up.This phenomenon is related to the recanalization and neovascular rectuitment of the residual AVMs, in which part of the vascular endothelial cells are not totally destroyed during the embolization procedure. The periodic clinical and imaging follow-up indicates that the recurrence of the AVMs after the ethanol embolization is not observed by the avoidance of the former mentioned phenomenon, by means of the direct toxic effect of the ethanol which denatures the blood protain and completely destroys the vascular endothelial cells. At present, the basic research of the changes of the vascular endothelial cells and the vascular smooth muscle cells after the ethanol embolization is rare. This study plans to evaluate the development and transformation of the vascular endothelial cells and the vascular smooth muscle cells of the AVMs after the ethanol embolization by the morphological and molecular biology research, which may provide the theoretical basis and technical guidance for the ethanol embolization of AVMs in clinical use.

动静脉畸形（又称为蔓状血管瘤）严重危害患者的身心健康，多发于口腔颌面部，介入栓塞是其首选的治疗方法。基于组织胶和PVA颗粒的栓塞，因栓塞后异常血管团内皮细胞仍可部分存活，并出现新生血管的形成和血管再通，而导致栓塞治疗后的复发相当普遍。无水酒精由于其脱水和剥蚀作用可使接触的血红蛋白变性并直接破坏血管内皮细胞，阶段性的临床及影像学随访显示，酒精栓塞治疗后动静脉畸形未见明显复发征象。但是，有关无水酒精栓塞治疗后，动静脉畸形内皮细胞及血管平滑肌细胞发展变化的基础研究相当匮乏。本研究拟对无水酒精栓塞治疗后异常血管团内皮细胞及血管平滑肌细胞的形态学及分子生物学变化进行探讨，以揭示其在无水酒精栓塞术后病变的发展及转归中的表现及作用。从而为临床上动静脉畸形的酒精栓塞治疗提供理论依据及技术指导。

动静脉畸形（AVMs）是一类难治的先天性血管病变。无水乙醇栓塞治疗AVMs已经成为目前该病最有效的治疗方法。肺动脉压力升高是无水乙醇栓塞治疗中常见的并发症，其可能是严重心肺血管意外的诱因之一。它的具体发生机制不清楚，本课题研究无水乙醇栓塞治疗诱发肺动脉损伤的可能机制及弹簧圈对于降低肺动脉压力升高风险的临床应用。使用家猪全麻下经颈静脉穿刺注射无水乙醇建立肺动脉高压的动物模型，将Swan-Ganz导管引至肺动脉监测压力值变化。在动物模型的基础上，将动物分为生理盐水组、乙醇组、生理盐水+氯沙坦组和乙醇+氯沙坦组，进行间隔7天的四次注射，然后，检测血浆中肾素、血管紧张素转移酶的活性、一氧化氮、丙二醛，血管紧张素Ⅰ和Ⅱ及肺动脉中的血管紧张素Ⅰ和Ⅱ。使用实时定量RT-PCR和免疫印迹方法检测肺动脉肾素-血管紧张素系统（RAS）、丝裂原活化蛋白激酶（MAPK）和NADPH 氧化酶成分的变化。同时，评价弹簧圈在AVMs患者无水乙醇栓塞治疗过程中降低肺动脉压力升高风险的临床效果。使用家猪经颈静脉注射无水乙醇可以模拟临床无水乙醇栓塞治疗诱导的肺动脉压力升高。无水乙醇静脉内注射可以激活肾素-血管紧张素系统，通过NADPH 氧化酶的激活导致肺动脉的氧化应激损伤。氯沙坦可以抑制无水乙醇诱导的肺动脉氧化应激损伤。无水乙醇经过氯沙坦介导MAPK磷酸化参与肺动脉氧化应激。临床研究发现，弹簧圈的应用可以减少栓塞治疗AVMs时无水乙醇的用量。无水乙醇诱导的肾素-血管紧张素系统激活，通过NADPH 氧化酶介导肺动脉氧化应激损伤。MAPK作为一个下游调控通路参与无水乙醇在氯沙坦介导下的氧化应激损伤。弹簧圈的应用可以减少无水乙醇的用量而降低栓塞治疗中肺动脉高压的风险。