内毒素在急性A型主动脉夹层全身炎症反应中关键机制研究

The clinical development process and laboratory findings of acute type A aortic dissection (AAAD) and severe acute pancreatitis (AP) were very similar, which performance of "inflammatory response→SIRS→MODS→Death", leading to MODS occurred and aortic rupture. The studies had confirmed that the endotoxin was the trigger of the SIRS occurred in pancreatitis, the endotoxin translocation caused a large number of inflammatory mediators released which prompted SIRS occurrence. This project is planned to establish a homogenization animal model that the intima was stripped consistently at the same time on the basis of original AAAD animal model by intraoperative vascular ultrasound, standardization original stripped area and the regulation of blood pressure. It is combining with the different time point degree of SIRS and the pathological observation and biomechanical testing of different part of aortic wall tissue, as well as the drug intervention around endotoxin to reduce the inflammatory response and improve aortic mechanical strength, in order to confirm that the endotoxin is the trigger of systemic inflammatory response in AAAD. We also analysis about the volume of the false lumen or elastic fiber layer exposing of the false lumen or blood flow regulation of the intestinal which was the initial factor of SIRS, to reveal the primary reason of SIRS in AAAD. It is expected to provide a new therapy theory to control SIRS progress and avoid the incidence of MODS and aortic ruptures, further to optimize the opportunity of surgery even improve the survival rate of AAAD patients.

急性A型主动脉夹层（AAAD）的临床发展过程和实验室发现与重症急性胰腺炎（AP）极为相似，表现"炎症反应→SIRS→MODS→死亡"，导致MODS发生和主动脉破裂。研究证实内毒素是胰腺炎中SIRS发生的扳机，内毒素移位导致大量炎症介质的释放促使SIRS的发生。本项目拟在前期动物模型基础上，通过术中血管超声、标准化原始剥离面积与控制血压等措施建立单位时间剥离范围一致的同质化AAAD动物模型，结合不同时点SIRS程度、不同部位的主动脉壁组织的病理观察和生物力学性能测试，以及围绕内毒素的药物干预对炎症反应和主动脉力学强度的改善情况，论证内毒素在AAAD全身炎症反应中的扳机作用，分析夹层假腔机械压迫、假腔弹力纤维层暴露以及肠道自身血流调节在SIRS发生过程中主次关系，揭示AAAD中全身炎症反应的始动因素。有望为控制AAAD中SIRS的进展，预防MODS发生及主动脉破裂，优化手术时机提供新的理论基础

内急性A型主动脉夹层（AAAD）的临床发展过程和实验室发现与重症急性胰腺炎（AP）极为相似，表现“炎症反应→SIRS→MODS→死亡”，导致MODS发生和主动脉破裂。研究证实内毒素是胰腺炎中SIRS发生的扳机，内毒素移位导致大量炎症介质的释放促使SIRS的发生。本项目通过术中血管超声、标准化原始剥离面积与控制血压等措施建立单位时间剥离范围一致的同质化AAAD动物模型，结合不同时点SIRS程度，以及围绕内毒素的药物干预对炎症反应强度的改善情况，论证内毒素在AAAD全身炎症反应中的扳机作用。结果证实急性Stanford A型主动脉夹层形成初期血液与假腔中膜组织接触后即引起血小板活化，随之出现中性粒细胞以及单核细胞激活。血小板活化以及中性粒细胞、单核细胞激活为急性Stanford A型主动脉夹层相关全身炎症反应综合症的初始机制；内毒素升高并不是触发机制，其升高后进一步加重了全身炎症反应综合症，最终导致多器官功能障碍的发生。通过抑制中性粒细胞、单核细胞激活，发挥抗炎作用，明显阻断了实验动物全身炎症反应综合征的发生并减轻了组织器官损伤，有望为控制AAAD中SIRS的进展，预防MODS发生及主动脉破裂，优化手术时机提供新的理论基础。

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