Sakai Hiromi, Tsuchida Eishun, Horinouchi Hirohisa, Kobayashi Koichi
Advanced Research Institute for Science and Engineering, Waseda University, Tokyo, Japan.
Artif Cells Blood Substit Immobil Biotechnol. 2007;35(1):81-91. doi: 10.1080/10731190600974582.
Hemoglobin-vesicles (HbV) or liposome-encapsulated Hb are artificial oxygen carriers. Our previous studies of the bolus infusion of HbV into Wistar rats showed that HbV was captured by the reticuloendothelial system from the blood stream and degraded completely with no deteriorative effect for 2 weeks. However, one authority on artificial organs research suggested conducting a one-year observation because he experienced, with one lipid-emulsified perfluorocarbon (PFC), that rats died within one year from a pulmonary abnormality after receiving the PFC emulsion due to the unstable dispersion state (personal communication). We thought this would never happen for HbV because the dispersion state of HbV is stable with PEG-modification. To confirm this, we made one-year observations after HbV infusion as suggested. Five male Wistar rats intravenously received 20 ml/kg HbV suspended in saline ([Hb] = 10 g/dL). They were housed in separated cages and provided with food and water ad libitum. All rats survived one year, and were apparently healthy. Their body weights (821+/-75 g) reflected obesity from their confinement in small cages. No histopathological abnormality was found in the lung. Plasma biochemical analyses showed overall normal organ functions. In our previous report, plasma lipid levels increased transiently at 1 or 2 days; then they reverted to the control level at 7 days. One year later, the rats showed much higher plasma lipid levels, a symptom of hyperlipidemia that is attributable to obesity and aging. It seemed the transient increases at the early days had no impact compared with the levels of hyperlipemia of the old rats.
血红蛋白囊泡（HbV）或脂质体包裹的血红蛋白是人工氧载体。我们之前将HbV大剂量注入Wistar大鼠的研究表明，HbV会被网状内皮系统从血流中捕获并完全降解，在2周内没有不良影响。然而，一位人工器官研究领域的权威人士建议进行为期一年的观察，因为他在研究一种脂质乳化全氟碳（PFC）时发现，大鼠在接受PFC乳剂后，由于其分散状态不稳定，在一年内死于肺部异常（个人交流）。我们认为HbV不会出现这种情况，因为经聚乙二醇（PEG）修饰后HbV的分散状态是稳定的。为了证实这一点，我们按照建议在注入HbV后进行了一年的观察。五只雄性Wistar大鼠静脉注射了20 ml/kg悬浮于生理盐水中的HbV（[Hb]=10 g/dL）。它们被饲养在单独的笼子里，随意提供食物和水。所有大鼠均存活了一年，且明显健康。它们的体重（821±75 g）反映出由于被关在小笼子里而出现肥胖。肺部未发现组织病理学异常。血浆生化分析显示器官功能总体正常。在我们之前的报告中，血浆脂质水平在第1天或第2天会短暂升高；然后在第7天恢复到对照水平。一年后，这些大鼠的血浆脂质水平高得多，这是高脂血症的症状，可归因于肥胖和衰老。与老年大鼠的高脂血症水平相比，早期的短暂升高似乎没有影响。
