A RESERACH ON DEVELOPMENT AND APPLICATION OF THE CLINICALLY APPRICABLE NEW ARTIFICIALRED BLOOD CELLAND ARTIFICIAL OXYGEN CARRIER

血红蛋白（Hb）修饰的人工红细胞由于其一氧化氮（NO）淬灭而具有临床上有问题的不良反应，例如血液升高或血小板活化和凝血。这是由于血红蛋白分子中的血红素吸收了内皮细胞或神经末梢释放的NO。在本研究中，我们开发了一种新的临床应用的血红蛋白修饰分子，其中其SH部分是s-亚硝基化，因此，可以释放NO。我们还开发了一种新的全氟化碳（PFC），通过使用新的挤奶机，这是在相同的大小融化，稳定，具有更好的生物利用度。1.初步设计了NO-PEG-Hb在脑缺血中的临床应用，并在大鼠2 VO模型中验证了其有效性。其机制可能是抑制iNOS合成的大量NO和NO-PEG-Hb释放NO。2.为了将新型PFC用作儿童人工体外循环的血浆扩张剂，我们进行了犬模拟实验，并从各种心功能方面认识其临床应用价值，3.我们认识到预防性应用新的PFC对心肌缺血再灌注损伤的效用，通过测量心脏的心律失常和生化参数，功能、心律失常和生化指标的变化。4.为了评价各种人工红细胞对脑缺血保存的影响，我们建立了一种新的大鼠认知评价方法。5.我们认识到，通过测量心功能，6.证实了NRC对脑缺血的保护作用。通过大鼠认知功能的评价方法。

Hemoglobin (Hb)-modified artificial red blood cell has clinically problematic adverse reactions such as blood elevation or activation of platelets and coagulation due to its nitric oxide (NO) quenching. This is derived from absorption of NO released from endothelial cells or nerve endings by heme of Hb molecule. In the present study we developed a new clinically applicable Hb modified molecule in which its SH moiety is s-nitrosylated, thus, can release NO. Also we developed a new perfluorocarbon (PFC) by using a new milking machine, which is melting in a equal sized, stable and with better bioavailability. We checked its bioavailability, clinical availability as an artificial oxygen carrier and artificial organ preserver.1.We planned the clinical application of NO-PEG-Hb to brain ischemia, and recognized its utility in rat 2VO model. Its mechanism seemed to quench large amount of NO synthesized by iNOS and also NO release from NO-PEG-Hb.2.To utilized the new PFC as a plasma expander for artificial cardiopulmonary bypass in children, we conduced a simulated experiment using dog and recognized its clinical utility from various cardiac functions, arrhythmias and biochemical parameters.3.We recognized that the utility of prophylactic application of the new PFC for cardiac ischemia reperfusion injury by measuring cardiac functions, arrhythmias and biochemical parameters.4.To evaluate effects of various artificial red blood cells on brain ischemia preservation we established a new evaluation method for cognition using the rat.5.We recognized that the utility of prophylactic application of a liposome-encapsulated hemoglobin, Neo Red Cell (NRC), for cardiac ischemia reperfusion injury by measuring cardiac functions, arrhythmias and biochemical parameters.6.We recognized the preserving effect of NRC on brain ischemia. by an evaluation method for cognitive function in the rat.