Liposome-encapsulated hemoglobin (hemoglobin-vesicle) is not transferred from mother to fetus at the late stage of pregnancy in the rat model.
Liposome-encapsulated hemoglobin (hemoglobin-vesicle) is not transferred from mother to fetus at the late stage of pregnancy in the rat model.
复制标题
在大鼠模型的妊娠后期，脂质体包裹的血红蛋白（血红蛋白囊泡）不会从母体转移到胎儿。
DOI：
10.1016/j.lfs.2012.08.021
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
and Yaegashi N.
中科院分区：
文献类型：
--
作者：
Kaga M;Li H;Ohta H;Taguchi K;Ogaki S;Izumi H;Inagaki M;Tsuchiya S;Okamura K;Otagiri M;Sakai H;and Yaegashi N.
目的脂质体封装的血红蛋白（血红蛋白囊泡：HbV；直径 250nm）由人血红蛋白重建，并开发为人造氧载体，用作输血替代品。先前使用啮齿动物模型的研究仔细研究了每日重复输注 (DRI) HbV 的安全性，并报道网状内皮系统在生理上能够降解 HbV，以将血浆临床化学维持在正常范围内。本研究探讨HbV DRI对妊娠大鼠母体和胎儿发育的影响，重点关注妊娠期HbV的胎盘转移。主要方法妊娠大鼠静脉推注HbV，剂量为2ml/kg/天，连续7天直至足月。累积输注量（14ml/kg）等于全血量（56ml/kg）的25%。关键发现HbV母体DRI对孕妇或胎儿发育没有明显副作用。 HbV DRI 后，母亲生命体征、血浆临床化学和血气参数总体正常。此外，HbV 的母体/胎儿转移仅限于胎盘，HbV 并未到达胎儿。使用人血红蛋白抗体进行的组织病理学检查发现，母体脾脏、肝脏、肾脏和胎盘中存在 HbV 积聚，但胎儿中未发现 HbV 积聚。使用 125 I 标记的 HbV 进行的药代动力学研究也证实了这些结果。 意义 这项针对怀孕母亲和胎儿使用 HbV 的安全性研究将有助于 HbV 通过胎盘供氧作为胎儿缺氧的潜在治疗方法。
AIMSLiposome-encapsulated hemoglobin (hemoglobin vesicles: HbV; diameter 250nm) is reconstructed from human hemoglobin and developed as an artificial oxygen carrier for use as a transfusion alternative. Previous studies using rodent models closely investigated the safety of daily repeated infusions (DRI) of HbV and reported that the reticuloendothelial system was physiologically capable of degrading HbV to maintain plasma clinical chemistry within normal ranges. The present study examined the effect of DRI of HbV on the pregnant rat mother and fetal development, focusing on placental transfer of HbV in pregnancy.MAIN METHODSPregnant rats intravenously received HbV bolus injections at 2ml/kg/day for the last 7 consecutive days till term. The cumulative infusion volume (14ml/kg) was equal to 25% of the whole blood volume (56ml/kg).KEY FINDINGSMaternal DRI of HbV had no obvious side effects on the pregnant mother or on fetal development. Maternal vital signs, plasma clinical chemistry, and blood gas parameters were overall normal after DRI of HbV. In addition, maternal/fetal transfer of HbV was limited to the placenta and HbV did not reach the fetus. Histopathological examination with human hemoglobin antibody detected HbV accumulation in the maternal spleen, liver, kidney, and placenta, but not in the fetuses. These results were also confirmed by a pharmacokinetic study using125I-labeled HbV.SIGNIFICANCEThis safety study of HbV use in the pregnant mother and fetus will contribute to a possible application of HbV as a potential treatment for fetal hypoxia by supplying oxygen through the placenta.