近年来，全球变暖已成为难以逆转的气候趋势；同时，随着我国工业化进程的加快，高温作业工人群体不断壮大；这直接导致越来越多的人不得不面临热应激的威胁。散热和供氧的双重需要导致心脏负荷急剧增加，继而引起心功能障碍，是热应激的重要病理生理特征之一。本研究拟在GRP75对热应激所致心肌细胞损伤具有保护作用这一重要前期发现的基础上，进一步确认GRP75对热应激心肌细胞的保护作用；研究GRP75对热应激心肌细胞Ca2＋代谢和线粒体能量代谢的调控作用及其时效性规律；研究Tom40对IP3R-GRP75-VDAC复合物的调节作用，阐明GRP75对热应激心肌细胞线粒体Ca2＋代谢和能量代谢调控的分子机制。探索通过调控GRP75水平防治热应激致心肌细胞损伤的可行性，从而揭示热应激致心肌细胞损伤的关键靶标分子，为不断壮大高温作业人群的心功能保护提供新的科学依据。

In recent years, the global temperature warming has become difficult to reverse climate trends. Same time, with the accelerated process of industrialization in China, the high-temperature operation growing groups of workers. This is a direct result of the growing number of people have to face the threat of heat stress. Heat stress lead to cardiac stress increased dramatically, thereby giving rise to cardiac dysfunction. In this study, based on preliminary experiments, we will confirmed the protective effect of GRP75 in cardiac dis function induced by heat stress. The GRP75 on Ca2 + metabolism and mitochondrial energy metabolism in myocytes of rats will be studied and the interaction of GRP75 and VDAC and IP3R will be realed in this study. The molecular basis of GRP75 in regulating Ca2 + metabolism and energy metabolism regulation of cardiomyocytes will be clarified. The result will provide some scientific evidence for revealing the cellular and molecular mechanism of GRP75 prevent cardic disfunction induced by heat stress.

近年来，高温作业工人群体不断壮大；这直接导致越来越多的人不得不面临热应激的威胁。心功能障碍是热应激的重要病理生理特征之一。本研究在GRP75对热应激所致心肌细胞损伤具有保护作用这一重要前期发现的基础上，进一步确认了GRP75对热应激心肌细胞的保护作用；探讨了GRP75对热应激心肌细胞Ca2＋代谢和线粒体能量代谢的调控作用及其时效性规律，发现GRP75对热应激心肌细胞的保护作用机制主要是通过调节线粒体Ca2＋代谢和能量代谢实现的，其机制可能与线粒体外模上的蛋白质复合物IP3R-GRP75-VDAC关系密切；在此基础上进一步研究了Tom40对线粒体Ca2＋代谢和能量代谢关键的蛋白质复合物IP3R-GRP75-VDAC的调节作用，阐明了GRP75对热应激心肌细胞线粒体Ca2＋代谢和能量代谢调控的分子机制。在此基础上，初步探索了通过调控GRP75水平防治热应激致心肌细胞损伤的可能性，从而揭示了热应激致心肌细胞损伤的关键靶标分子，为不断壮大高温作业人群的心功能保护提供了新的科学依据。