重组人血小板生长因子促进受照射小鼠巨核系和红系造血的恢复(英文)

Recombinant Human Thrombopoietin Enhances Megakaryocytopoietic and Erythropoietic Restoration in Irradiated Mice

血小板生长因子(TPO)是巨核细胞系唯一的特异性生理性正调控因子。它可诱导造血干、祖细胞向巨核细胞系分化,促进巨核细胞的发育成熟及血小板的生成和释放。为了研究TPO的生物活性,我们给^(60)Co照射小鼠腹腔注射重组入TPO (rhTPO),每天0.2mg/kg体重或0.3mg/kg体重,连续20天。检测了小鼠的外周血象及骨髓造血祖细胞的培养。结果rhTPO治疗组小鼠的外周血血小板计数下降较慢,并且提前恢复,尤其是在0.3mg/kg体重组(P<0.05-P<0.01)。骨髓造血祖细胞培养见rhTPO治疗组小鼠的骨髓CFU-MK和BFU-E(10天),较对照组明显增高(P<0.01)。骨髓GM-CFU与对照组比较无显著差别。因此,我们认为rhTPO可促进受照小鼠巨核细胞系和红细胞系造血的重建,是临床治疗骨髓抑制性血小板减少的有希望的生物治疗药物。

Thrombopoietin (TPO) is a normal physiological hematopoiesis factor which is able to stimulate the hematopoietic progenitor cells to proliferate and differentiate into megakaryocytes and to induce the production and release of platelets. In order to study the biological activities of human TPO (hTPO), we administered recombinant hTPO (rhTPO) to 5.0 Gy γ- irradiated mice once daily for 20 consecutive days at dosages of 0.2 and 0.3 mg/kg of body weight. Bone marrow was assayed for clonogenic activity and peripheral blood counts were monitored. As a result, circulating platelet counts of rhTPO treated mice decreased less and restorated earlier than that of irradiated control mice, especially in rhTPO 0.3 mg/kg of body weight group (f < 0.05 - F < 0.01). Bone marrow derived clonogenic data showed significant increasing in the number of CFU-MK and BFU-E-day 10 in rhTPO 0.3 mg/kg of body weight treated mice (P<0.01). The granulocyte-macrophage restoration of rhTPO treated mice did not show significant difference as compared with that of irradiated control group. In conclusion, rhTPO is a potent stimulator of thrombocy-topoiesis and erythropoiesis in the states of myelosuppression and an effective biological therapy for irradiation induced thrombocytopenia.