重组人血小板生成素早期干预救治重症急性放射病猴的实验研究

重组人血小板生成素（rhTPO）是一种能促进巨核系祖细胞增殖、分化生成血小板的造血因子,研究表明它能促进射线照射小鼠造血功能恢复,前期工作证明rhTPO早期干预可显著提高致死剂量照射小鼠的活存率.本文以7.0Gy照射恒河猴为重度骨髓型急性放射病（ARS）模型,研究了rhTPO早期干预对重症ARS的治疗作用,并与WR2721和＂500＂的辐射防护作用进行了比较,结果发现rhTPO早期干预可明显促进ARS猴造血功能恢复,改善ARS猴症状,简化对症治疗措施,提高重度骨髓型ARS猴活存率,其对重度骨髓型ARS的防治作用优于现有的辐射防护药WR2721和＂500＂,有望开发成安全有效的新型辐射防治药物.

Administration of Recombinant Human Thrombopoietin Soon after Irradiation Promotes Survival and Stimulates Hematopoietic Recovery in a Nonhuman Primate Model of Radiation-Induced Severe Acute Radiation Syndrome

Accidental or intentional irradiation causes incidents involving acute radiation syndrome (ARS) victims. Thus, it is urgent to search for effective radioprotectors with no or low toxicity. Recombinant human thrombopoietin (rhTPO) is a megakaryocyte colony-stimulating factor. We have demonstrated previously that early administration of rhTPO soon after irradiation promotes survival of lethal dose irradiated mice. To evaluate the therapeutic effect of rhTPO short-term injection soon after radiation in nonhuman primates exposed to a high dose of gamma ray, rhesus monkeys received subcutaneously of early rhTPO 10 μg/kg injection at 0.5 and 24 h after or WR2721 30 mg/kg intramuscularly administration at 0.5 h before total body irradiated (TBI) with a 7 Gy gamma dose. Survival was monitored and hematopoiesis was evaluated at 40 d following early treatment. rhTPO short-term early injection (0.5 and 24 h) after 7 Gy TBI induced 100.0% survival versus 33.3% in irradiated controls, while 83.3% in WR2721 protected monkeys. rhTPO early treatment significantly promoted hematopoiesis recovery and apparently improved the quality of life, and additionally simplified supportive care in ARS rhesus monkeys. According to the survival and hematopoiesis of irradiated nonhuman primates, radioprotection of rhTPO short-term injection soon after TBI is better than WR2721 administration at 0.5 h before TBI. Thus short-term injection of rhTPO soon after irradiation might be chosen as a first-line therapeutic strategy in the treatment of accidental acute radiation victims.