超高海拔低氧对心脏能量代谢重编程的影响和心脏保护研究

超高海拔下的低氧是高原人群面临的主要环境应激。在此特殊环境下，心脏的能量代谢将被迫重编程来适应环境的剧烈改变。因此加强心功能保护，促进旅居者快速适应和延长世居者寿命已成为国家的重大战略需求。课题组长期从事低氧对全身生理影响的临床和转化医学研究。在前期工作中我们发现低氧诱导因子1α（HIF1α）在长期低氧动物中心脏能量代谢模式转变中的作用。在本课题中，结合西藏林芝地区超高海拔地区的世居者和援藏人员队列，利用低压低氧下急性和慢性动物模型，开展一系列心脏能量代谢的研究。本研究将具体回答“HIF1α调控通路在不同高原人群中将发生何种改变来促进心脏能量代谢重编程“这个关键科学问题。本研究拟从系统生物学角度出发，解析西藏旅居和世居者的心脏能量代谢规律，从而为入藏人员健康筛选、无创无非药物手段加速其适应提出若干行之有效的干预策略，为世居者甄别心衰高危因素，提前药物干预提供流行病学和转化医学证据。

The diminished ambient oxygen pressure of very high altitude is known as the main environmental stimulus to highlanders. With the exposure of hypobaric hypoxia, the cardiac energy metabolism was reprogramed to acclimatize to the severe environment. Therefore, it’s of great value to develop the related cardioprotection strategies to promote sojourners acclimatization and extend life-span of permanent residents of very high altitude locations. Our previous studies indicated that hypoxia-inducible factor 1α (HIF1α) is critical in cardiac metabolic remodeling in response to chronic hypoxia. In this study, we conducted series of research on cardiac energy metabolism based on both animal experiments and clinical cohorts of native Tibetan and cadres sent to support Tibet, and try to elucidate how HIF1α was modulated in different clusters of highlanders to induce the cardiac metabolic remodeling. Furthermore, we try to delineate the distinct cardiac metabolic patterns of native Tibetan and sojourners, so as to provide solid evidence for translational medicine when developing personalized cardioprotection strategies to promote sojourners acclimatization, to identify risk factors for heart failure and develop drug prophylaxis for permanent residents of very high altitude locations.