Thrombopoietin promotes hematopoietic recovery and survival after high-dose whole body irradiation
Thrombopoietin promotes hematopoietic recovery and survival after high-dose whole body irradiation
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DOI：
10.1016/s0360-3016(98)00477-5
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发表时间：
1999-03-01
影响因子：
7
通讯作者：
Wagemaker, G
中科院分区：
文献类型：
--
作者：
Mouthon, MA;van der Meeren, A;Wagemaker, G
目的：探讨血小板生成的主要调节因子--血小板生成素(TPO)对致死性和超致死性全身照射(TBI)后小鼠的造血恢复和存活的影响。方法与材料：C57BL6/J小鼠经8Gy射线全身照射后，进行存活实验。对两种给药方案进行了评价：照射后2 h开始连续给药7天(7×0.3 mU/只)，或照射后2 h单次给药(0.3 mU/只)。结果：与安慰剂组相比，TPO能改善受照小鼠的血小板最低点，促进血小板重建。中性粒细胞和红细胞的恢复也得到刺激。TPO可促进骨髓和脾中造血祖细胞和未成熟多系祖细胞的恢复。此外，TPO可诱导8Gy射线照射的C57BL6/J小鼠约90%的存活率，这一TBI剂量可导致安慰剂组小鼠30天内100%的死亡率。TPO单次给药在恢复造血和预防死亡方面与重复注射同样有效。在BCBA F-1小鼠身上进行的剂量-效应存活实验表明，TPO使单次给药的LD50/30从9.5Gy移至10.5GyTBI，当分三次等剂量给药时，LD50/30从14Gy高达17Gy.结论：TPO的多系造血作用可能有利于预防大剂量脑损伤后的致死性骨髓衰竭，(C)1999 Elsevier Science Inc.
Purpose: The therapeutic potential of thrombopoietin (TPO), the major regulator of platelet production, was evaluated for hematopoietic recovery and survival in mice following; lethal and supralethal total body irradiation (TBI),Methods and Materials: Hematopoietic recovery was studied in C57BL6/J mice after 8 Gy TBI (gamma-rays), Survival experiments were performed with C57BL6/J and BCBA F-1, mice. Two protocols of TPO administration were evaluated: treatment for 7 consecutive days (7 x 0.3 mu g/mice) beginning 2 h after exposure, or a single dose (0.3 mu g/mice) administered 2 h after irradiation.Results: TPO improved the platelet nadir and accelerated the platelet reconstitution of irradiated mice in comparison to placebo-treated mice. Recovery of neutrophils and erythrocytes was stimulated as well. TPO induced an accelerated recovery of hematopoietic progenitors and immature multilineage progenitors in bone marrow and spleen. In addition, TPO administration induced approximately 90% survival of 8 Gy irradiated C57BL6/J mice, a TBI dose which resulted in 100% mortality within 30 days for placebo-treated mice. Single TPO administration was as effective as repeated injections for hematopoietic recovery and prevention of mortality. Dose-effect survival experiments were performed in BCBA F-1, mice and demonstrated that TPO shifted the LD50/30 from approximately 9.5 Gy to 10.5 Gy TBI given as a single dose, and from 14 Gy to as high as 17 Gy when TBI was given in three equal doses, each separated by 24 h,Conclusion: These results demonstrate that the multilineage hematopoietic effects of TPO may be advantageously used to protect against lethal bone marrow failure following high dose TBI, (C) 1999 Elsevier Science Inc.