Fukumoto Dai, Kawaguchi Akira T, Haida Munetaka, Yamano Mariko, Ogata Yoshitaka, Tsukada Hideo
Hamamatsu Photonics K.K., Hamamatsu, Japan.
Artif Organs. 2009 Feb;33(2):159-63. doi: 10.1111/j.1525-1594.2008.00701.x.
Liposome-encapsulated hemoglobin (LEH) with a low oxygen affinity (l-LEH, P(50) = 45 mm Hg) was found to be protective in the rodent and primate models of ischemic stroke. This study investigated the role of LEH with a high O(2) affinity (h-LEH, P(50) = 10 mm Hg) in its protective effect on brain ischemia. The extent of cerebral infarction was determined 24 h after photochemically induced thrombosis of the middle cerebral artery from the integrated area of infarction detected by triphenyltetrazolium chloride staining in rats receiving various doses of h-LEH as well as l-LEH. Both h-LEH and l-LEH significantly reduced the extent of cortical infarction. h-LEH remained protective at a lower concentration (minimal effective dose [MED]: 0.08 mL/kg) than l-LEH (MED: 2 mL/kg) in the cortex. h-LEH reduced the infarction extent in basal ganglia as well (MED: 0.4 mL/kg), whereas l-LEH provided no significant protection. h-LEH provided better protection than l-LEH. The protective effect of both high- and low-affinity LEH may suggest the importance of its small particle size (230 nm) as compared to red blood cells. The superiority of h-LEH over l-LEH supports an optimal O(2) delivery to the ischemic penumbra as the mechanism of action in protecting against brain ischemia and reperfusion.
低氧亲和力的脂质体包裹血红蛋白（LEH，l-LEH，P(50) = 45 mmHg）在缺血性中风的啮齿动物和灵长类动物模型中具有保护作用。本研究调查了高氧亲和力的LEH（h-LEH，P(50) = 10 mmHg）对脑缺血的保护作用。在接受不同剂量h-LEH以及l-LEH的大鼠中，通过三苯基四氮唑氯化物染色检测梗死综合面积，在大脑中动脉光化学诱导血栓形成24小时后确定脑梗死范围。h-LEH和l-LEH均显著降低了皮质梗死范围。在皮质中，h-LEH在比l-LEH更低的浓度（最小有效剂量[MED]：0.08 mL/kg）下仍具有保护作用（l-LEH的MED：2 mL/kg）。h-LEH也降低了基底神经节的梗死范围（MED：0.4 mL/kg），而l-LEH没有提供显著保护。h-LEH比l-LEH提供了更好的保护。高亲和力和低亲和力LEH的保护作用可能表明与红细胞相比，其小粒径（230 nm）的重要性。h-LEH优于l-LEH支持向缺血半暗带最佳输送氧气作为预防脑缺血和再灌注的作用机制。
