急性低氧影响大鼠脑血流动力学的机制研究

High altitude cerebral edema (HACE) is the most dangerous altitude sickness and high mortality. HACE was considered as cytotoxicedema mainly in the past. But more and more evidence suggests suggested that HACE is probable angioedema. It will be directly related to select these measures of prevention and treatment of HACE that which type of edema is dominant. We compare the hemodynamics indicators of cerebral by different vasoactive substances blocker under different oxygen environment, and combine with the overall hemodynamic changes to investigate the mechanism of occurrence and development of HACE. To investigate the biochemistry, blood gas, the expression of cerebrovascular occludin, brain tissue morphology and ultrastructure, and redox level of brain under the different oxygen environments, to analyze the type of edema and cerebral hemodynamics mechanism. This study will exposit the initiating keys of HACE’s occurrence and development process by analyzing the changes of cerebral vascular resistance and cerebral oxygen consumption, and combined with the overall hemodynamic changes in different hypoxia on cerebral hemodynamics and cerebral metabolic function. Completion of the research will be providing an important theoretical basis for the prevention and treatment of HACE, and the research results of this basic theory has further clinical utility.

高原性脑水肿（HACE, high altitude cerebral edema）在高原病中最为凶险、病死率高。过去仅认为HACE主要是细胞中毒性脑水肿，但越来越多的证据表明它的形成过程中也伴有血管源性脑水肿，对于HACE到底是以哪种类型水肿占主导优势直接关系到HACE的有效预防和治疗措施的选择。本课题通过应用不同血管活性因子干预，实时、动态地对比观察不同低氧下脑的血流动力学指标，并对不同急性低氧环境下大鼠血液生化、血气、脑血管Occludin 蛋白表达、脑组织形态及超微结构和脑氧化还原水平的观察，结合全身血流动力学的改变，探索HACE在其发生、发展过程中不同急性低氧影响脑水肿的类型和脑血流动力学变化机制。经过观察低氧下脑血管阻力和脑耗氧量的改变，分析不同程度急性低氧对脑血流动力学和脑代谢功能的影响，揭示HACE发生发展的始动环节，这将为预防和治疗HACE提供更具有临床实用性的理论。

高原脑水肿（HACE）在高原病中最为凶险、病死率高，并且对HACE的形成机制的了解直接关系到对HACE的有效预防和治疗措施的选择。本课题通过建立测量大鼠脑血管阻力的动物模型和急性低氧引起HACE的大鼠脑血流动力学实时、动态监测模型，对比观察了不同低氧下和应用不同血管活性因子干预时脑的血流动力学指标，并对不同急性低氧环境下大鼠的血液生化、血气指标及脑血管Occludin蛋白的表达、脑组织形态及超微结构和脑组织的氧化还原水平进行了研究。从中发现，应用β受体阻断剂和双侧肾上腺切除等方法干预会明显增加脑血管阻力，和其他缩血管类活性剂（组胺、抗利尿激素、血管紧张素、NOS阻断剂）应用有协同作用，说明内源性NO的释放和交感肾上腺素系统的激活在HACE 的发生、发展中起着重要的代偿调节作用。通过检测不同海拔高度和不同低氧处理时间大鼠脑组织中Occludin 蛋白表达和组织学及超微结构的观察，脑组织形态学结构异常改变与脑组织中Occludin 蛋白表达呈负相关，在模拟海拔8000m 缺氧12小时时损害程度最为明显。预示着严重缺氧会较少脑血管Occludin 蛋白的表达，破坏血脑屏障的完整性、促进脑水肿的发生。这将为预防和治疗HACE提供更实用的理论依据。