SGER: Development of a Perfused Heart Model for Heat Shock Protein Preconditioning

医学和科学界的大量经验数据表明，遭受轻度热应激的细胞会过度表达热休克蛋白（HSP），而热休克蛋白对受伤的细胞和组织具有保护和修复作用。我们已经完成了广泛的定量测量，热刺激条件最适合热休克蛋白在细胞培养中的表达。本提案提出了一套独特的实验，旨在通过建立一个新的方案来生产和测量整个器官模型中热休克蛋白的表达，将该技术发展到下一个水平。实验是基于现有的灌注工作大鼠心脏模型，由我们的一位医学院同事开发和使用了20多年。热应激将由微波源辐照产生，这是非常适合适应灌注装置和产生一个均匀的能量吸收场在整个大鼠心脏。整个器官研究的第一个方面的重点是确定测量大鼠心脏中热休克蛋白产生的有效性，并将灌注试验的持续时间延长到尽可能长的时间。我们将采用新颖的测量技术，通过多平面磁共振温度成像（MRTI）来量化心脏中的时间热场。虽然我们的实验室在生物热传递研究方面有几十年的经验，但这个项目是对一个全新研究领域的首次尝试，这个领域在世界上任何地方都没有现有的经验（据我们所知）。分子生物学领域的最新发展使这项工作成为可能，并且该项目在医学应用方面具有巨大的潜在最终回报。该合同由化学和运输系统分部的热传输和热处理项目资助。

Extensive empirical data within the medical and scientific communities indicate that cells subjected to mild thermal stress will over-express heat shock proteins (HSP), which are known to have protective and reparative effects on injured cells and tissues. We have completed extensive quantitative measurements of the thermal stimulation conditions optimal to HSP expression in cell cultures. This proposal presents a unique set of experiments designed to take this technology to the next level of development by establishing a new protocol for producing and measuring HSP expression in a whole organ model. The experiments are based on an existing perfused working rat heart model developed and used by one of our medical school colleagues for more than two decades. Thermal stress will be produced by irradiation with a microwave source, which is well suited for adaptation to the perfusion rig and to producing a uniform energy absorption field throughout a rat heart. The focus of this first aspect of the whole organ study is to determine the effectiveness of measuring HSP production in a rat heart and of extending the duration of the perfusion trial to as long a period as possible. We will implement novel measurement techniques to quantify the temporal thermal field, via multiplanar magnetic resonance temperature imaging (MRTI), in the heart. Although we have several decades of experience in bioheat transfer research in our laboratory, this project is the initial foray into a brand new domain of study in which there is no existing experience anywhere in the world (to our knowledge.) Recent developments in the field of molecular biology have made this work possible, and the project has a huge potential eventual payoff in medical applications. The award has been funded by the Thermal Transport and Thermal Processing Program of the Chemical and Transport Systems Division.