Chien Sufan
Department of Surgery, University of Louisville, Louisville, KY, USA.
Methods Mol Biol. 2010;605:377-91. doi: 10.1007/978-1-60327-360-2_26.
Healthy cells must maintain a high content of adenosine triphosphate (ATP) because almost all energy-requiring processes in cells are driven, either directly or indirectly, by hydrolysis of ATP. During ischemia or hypoxia, reduced blood flow or disturbed oxygen supply results in the disrupted balance of energy production and utilization, and depletion of high-energy phosphates is the fundamental cause of cell damage. Direct intravenous infusion of high-energy phosphates, such as adenosine triphosphate (ATP), has not produced a consistent result because strongly charged molecules like ATP normally cannot pass the cell membrane in sufficient quantities to satisfy tissue metabolic requirements. Furthermore, the half-life of free ATP in blood circulation is very short, limiting its efficacy as a bioenergetic substrate. We have developed a new technique for intracellular delivery of high-energy phosphate into normal or ischemic cells by using specially formulated, highly fusogenic, unilamellar lipid vesicles that contain magnesium-ATP. In vitro studies indicated a rapid fusion with the endothelial cells, protection of endothelial cells, and cardiomyocytes during ischemia. In vivo studies have shown enhanced full-thickness skin wound healing in various animal models. This technique has the potential to reduce or eliminate many detrimental effects caused by ischemia or hypoxia.
健康细胞必须维持高含量的三磷酸腺苷（ATP），因为细胞内几乎所有需要能量的过程都直接或间接地由ATP水解驱动。在缺血或缺氧期间，血流减少或氧气供应紊乱会导致能量产生和利用的平衡被破坏，而高能磷酸盐的耗竭是细胞损伤的根本原因。直接静脉输注高能磷酸盐，如三磷酸腺苷（ATP），并未产生一致的结果，因为像ATP这样带强电荷的分子通常不能以足够的量穿过细胞膜来满足组织代谢需求。此外，游离ATP在血液循环中的半衰期非常短，限制了其作为生物能量底物的功效。我们已经开发出一种新技术，通过使用特别配制的、高度融合的、含有镁 - ATP的单层脂质体，将高能磷酸盐细胞内递送至正常或缺血细胞中。体外研究表明，在缺血期间，脂质体与内皮细胞快速融合，对内皮细胞和心肌细胞具有保护作用。体内研究表明，在各种动物模型中，全层皮肤伤口愈合得到增强。这项技术有可能减少或消除由缺血或缺氧引起的许多有害影响。
