报告题目Title: Shedding Light on Mitochondrial Function In Vivo:Past Overview and Future Perspectives 用光学方法解释活体线粒体功能:总结与展望 报告人Speaker:以色列巴依兰大学Avraham Mayevsky教授 时 间Time: 2009年11月11号晚上7:00 地 点Venue: 光电实验室A101 简介 Biography: Mayevsky教授现任巴依兰大学生命科学系教授,是世界公认的在活体用光学技术监测线粒体活性(NADH氧化还原状态)和其他生理参数的专家。他是国际脑血流与代谢学会、国际氧向组织运输学会、欧洲神经科学联盟、欧洲微循环学会、以色列生理药理学会、以色列神经科学学会等组织的会员。在过去的35年里,他已经在这个领域发表了170多篇论文。 Mayevsky教授开发了一种在不同病理生理条件下实时监测大脑和其他器官(肾,肝,肠,脊髓,和睾丸)的独一无二的多参数监测仪器。这套多参数监测仪器包括荧光和激光多普勒监测的光导纤维,监测细胞外K+、Ca2+和H+水平的微型电极,监测颅内压的卡米诺探针,脑电图电极和监测组织温度的特殊热敏电阻。除此之外,Mayevsky教授和他的同事所组成的团队是唯一一个能实时同时监测线粒体NADH氧化还原状态、组织血流和氧合血红蛋白的团队。这一独特的方法提供了与主要临床病理状态密切相关的条件下组织水平关于氧的供需平衡至关重要的信息,包括病人在重症监护病房和手术室中的一些病理条件。 报告摘要Abstract: 自一百二十多年前线粒体被发现以来,理解线粒体的功能就成为对众多科学家们的挑战。一百多年前Harden和Young对吡啶核苷酸(也称为NADH)的描述促成了三十多年后Warburg及其合作者对吡啶核苷酸结构的完整理解。1955年,Chance和Williams的创新性工作第一次定义了体外分离出来的线粒体的代谢状态,并将这些状态与包括NADH在内的参与呼吸链的酶的氧化还原水平关联起来。Chance和他的合作者通过在活体监测NADH荧光,详细解释了这些状态的生理学意义,带动发表了1000多篇体外和在体监测NADH荧光的相关文章。近期,这一技术已经用于手术期间和重症监护病房的临床应用。在这一讲中,我将总结本人近40年的对线粒体氧化还原状态和活体组织功能的理解和工作。 正常的线粒体功能是维持人体不同器官中细胞平衡的重要因素。由于在很多病理状态下会产生线粒体失调,实时在体监测线粒体的代谢状态显得尤其重要。在动物模型和病人上进行这种监测可提供实时数据,帮助解释实验结果或优化病人的治疗。组织中NADH水平的监测可以以能量产生和细胞内含氧水平的方式为线粒体代谢状态的描述提供最重要的信息。在监测NADH的同时,我们用光学方法监测了同一组织区域的微循环血流和血容及氧合血红蛋白的氧化。这四个参数可以提供组织活力的实时数据,对病人的监护有重要作用。
Understanding the mitochondrial function has been a challenge for many investigators, since its discovery more than 120 years ago. The description of pyridine nucleotides (i.e. NADH) by Harden and Young 100 years ago led the complete understanding of their structure by Warburg and collaborators 30 years later. In 1955, the seminal work of Chance and Williams defined for the first time the metabolic states of isolated mitochondria in vitro, and correlated these states to the oxidation-reduction levels of respiratory enzymes including the NADH. The physiological significance of these metabolic states was elaborated, by Chance and collaborators, to the In Vivo monitoring of NADH fluorescence resulted in 1,000 relevant publications on NADH fluorescence monitored in vitro and in vivo. More recently, this technique was adapted for clinical applications (in intra-operative and intensive care units). In this lecture I will summarize my almost 40 years of activities and contributions to the understanding of mitochondrial redox state and tissue functions In Vivo. Normal mitochondrial function is a critical factor in maintaining cellular homeostasis in various organs of the body. Due to the involvement of mitochondrial dysfunction in many pathological states, the real-time in vivo monitoring of the mitochondrial metabolic state is crucially important. This type of monitoring in animal models as well as in patients provides real-time data that can help interpret experimental results or optimize patient treatment. The monitoring of NADH levels in the tissue provides the most important information on the metabolic state of the mitochondria in terms of energy production and intracellular oxygen levels. In addition to NADH, we measured, optically, the microcirculatory blood flow and volume, as well as HbO2 oxygenation, from the same tissue area. The four detected parameters provide real time data on tissue viability, which is critical for patients monitoring.
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