急性缺氧过程中脑部能量代谢与微循环的关联研究

发布时间：2018-05-20 21:35

本文选题：急性缺氧 + 脑部能量代谢　；参考：《华中科技大学》2014年博士论文

【摘要】：脑是维持机体生命活动的重要中枢。人的大脑有约1000亿个神经元,神经活动所需的能量来自于脑部的供血供氧。这个庞大而复杂的系统的运行机制与脑部的微循环和能量代谢密切相关,受到研究人员的持续关注。随着科学技术的发展,多种研究手段应运而生,从血氧与组织水平、线粒体水平、分子水平等不同层次揭示脑部能量代谢与微循环的动态关系。能量代谢的发生在细胞内,线粒体是能量的主要加工厂。利用线粒体氧化还原呼吸链上位于最上游的还原型烟酰胺腺嘌呤二核苷酸(reduced nicotinamide adenine dinucleotide, NADH)的自发荧光性质,可以灵敏地检测线粒体的氧化还原状态,从而表征细胞的能量代谢。而体循环和局部循环通常会改变脑部微循环,从而影响能量代谢。因此,同步测量体循环的变化,可以对微循环变化所影响的能量代谢变化提供更全面的解释。本文在Chance和Mayevsky等人创立和发展的NADH荧光测量系统的基础上,建立了一套新的跨层次、多参数监测方法,实现了同步检测大鼠脑皮层的NADH荧光、激发波长下的反射光、脑血流流速和全身的呼吸和心电变化。为了系统地研究能量代谢与脑部微循环的关系,本文采用了急性缺氧的模型,并从氧在体内传输和吸收的四个环节着手,分别进行干预,建立了乏氧性、血液性、循环性和组织性四类六种急性缺氧模型,具体分析了不同因素导致的不同类型缺氧发生时,线粒体、微循环、体循环等多个层次的信号变化。从时间发生的先后顺序可以推测能量代谢与微循环之间的相互影响。本文的结果证实：在正常麻醉状态下,大鼠脑皮层的代谢状态处于66.1%-73.0%之间；在死亡时,大鼠脑皮层的NADH可以上升到136.9%-151.4%；在缺氧时,脑血流最高可上升至(195.5±14.9)%,而脑血容的最大增幅不超过(55.0±2.4)%。脑血流的变化幅度比脑血容大。对于缺氧时是否出现毛细血管新增的这一争议性问题,本文发现,在乏氧性和血液性缺氧的两个模型中,缺氧发生时最先变化的是脑血容,然后才是脑血流,说明此时的脑血容变化是毛细血管开放数量增加造成的。从测量的五个参数的测量结果中,本文分析了能量代谢与微循环的关联情况。结果表明,NADH对缺氧的响应时间与缺氧的类型有关,亦即取决于缺氧的诱因。如果仅比较局部能量代谢与微循环的关联,NADH先于脑血流/脑血容发生变化,提示能量代谢先发生变化,其次微循环产生自我调节作用。由于缺氧的诱因不同,NADH信号并不能保持一贯的较早响应的优势。但多参数同时监测可以弥补漏检的风险。通过对四类六种的急性缺氧模型的研究,提示NADH参数具有一定的临床指导意义,表现为NADH信号预警的发生比其他参数要早。如果采取合理抢救,恢复供氧,机体可以免于死亡。因此,正确判断NADH到达极值的时间和正确判断缺氧类型(诱因)对于临床重症监护尤为重要。本文的研究提示,NADH升高到130%或进入明显平台期可作为预警信号之一。由于监护的对象和器官具有不同的氧化还原状态性质,具体的报警水平需要进一步的深入研究才能确定。同样,正确判断缺氧诱因则需要综合多参数的变化特征来考量。
[Abstract]:The brain is an important center to maintain the life of the body. The human brain has about 100 billion neurons, and the energy required for the nerve activity comes from the blood supply and supply of oxygen in the brain. The operation mechanism of this huge and complex system is closely related to the microcirculation and energy metabolism of the brain. A variety of research means emerge as the times require. The dynamic relationship between brain energy metabolism and microcirculation is revealed from different levels of blood oxygen and tissue level, mitochondrial level and molecular level. Energy metabolism occurs in cells, mitochondria are the main processing plants of energy, and the most upstream prototyping nicotinamide is located on the upper reaches of the original respiratory chain by mitochondria oxidation. The spontaneous fluorescence properties of reduced nicotinamide adenine dinucleotide (NADH) can sensitively detect the redox state of the mitochondria and characterize the energy metabolism of the cells. The body circulation and local circulation usually change the microcirculation of the brain, thus affecting the energy metabolism. It can provide a more comprehensive explanation for the changes of energy metabolism that affect the microcirculation.
On the basis of the NADH fluorescence measurement system created and developed by Chance and Mayevsky and others, a new multilevel and multi parameter monitoring method has been established to synchronize the NADH fluorescence of the rat cerebral cortex, the reflected light at the excitation wavelength, the flow velocity of the brain and the changes of the whole body respiration and electrocardiogram. In order to systematically study the energy metabolism, the system can systematically study the energy metabolism. In relation to the microcirculation of the brain, this article adopts the model of acute hypoxia, and begins with the four links of oxygen transmission and absorption in the body. We have intervened respectively, and established four kinds of acute hypoxia models of hypoxia, blood, circulatory and tissue, and analyzed the mitochondria and microorganism of different types of hypoxia caused by different factors. Multiple levels of signal changes, such as circulation, body circulation, etc., can be used to infer the interaction between energy metabolism and microcirculation from the order of time.
The results showed that the metabolic state of the cerebral cortex was between 66.1%-73.0% and NADH in the normal anesthetic state; the cerebral cortex of the rat could rise to 136.9%-151.4% at the time of death; the maximum cerebral blood flow could rise to (195.5 + 14.9)% at the time of hypoxia, while the maximum increase of cerebral blood volume was not more than (55 + 2.4)%. It's bigger than brain blood.
For the controversial question of whether the capillaries are newly added to the hypoxia, we find that in the two models of hypoxia and blood hypoxia, the first change is the volume of brain blood, then the cerebral blood flow, indicating that the changes in the volume of brain blood are caused by the increase in the amount of capillary opening.
The relationship between energy metabolism and microcirculation was analyzed from the measured results of five parameters. The results showed that the response time of NADH to anoxia was related to the type of anoxia, that is, the inducement of hypoxia. If only the correlation between local energy metabolism and microcirculation was compared, NADH was preceded by changes in cerebral blood flow / cerebral blood volume. The energy metabolism changes first and the second microcirculation produces self-regulation. Due to the Different Inducements of hypoxia, the NADH signal does not maintain the advantage of the consistent earlier response. However, multi parameter simultaneous monitoring can make up the risk of leakage.
Through the study of the acute hypoxia model of four kinds of six kinds, it is suggested that the NADH parameter has certain clinical guiding significance, which shows that the occurrence of NADH signal early warning is earlier than the other parameters. If reasonable rescue, recovery of oxygen supply, the body can be exempt from death. Therefore, the correct judgment of the time to reach the extreme value of NADH and the correct judgement of the type of anoxia (inducement) It is particularly important for clinical intensive care. The study in this paper suggests that the rise of NADH to 130% or a clear platform can be one of the early warning signals. Due to the different redox state properties of the objects and organs of the guardianship, the specific alarm level needs further study to determine. The change characteristics of multiple parameters are required to be considered.
【学位授予单位】：华中科技大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R742

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