重组融合蛋白rTMP—GH促进放射损伤小鼠血小板生成的实验研究

Effect of rTMP-GH recombinant fusion protein on thrombocytopoiesis in irradiation injured mice

目的研究TPO模拟肽（TMP）与人生长激素（GH）的重组融合蛋白rTMP-GH对放射损伤小鼠血小板生成的促进作用。方法^60Coγ射线全身一次性均匀照射5Gy，照后皮下注射200μg／kg的rTMP—GH或rhGH，每日1次，连续用药7d，对照组给予同等体积生理盐水。尾静脉取血检测血小板数量变化；照后16d取小鼠股骨，组织切片观察骨髓病理变化。结果照后10d起，rTMP-GH处理组各时相的外周血血小板数明显高于rhGH处理组和生理盐水对照组，尤其是血小板的最低值显著升高（P〈0．01），照后22d已升至正常水平的80％，对照组仅为30％。骨髓病理观察显示，rTMP—GH处理组骨髓造血重建明显，并见大量不同时期巨核细胞；rTMP-GH处理组骨髓组织切片每个视野下的巨核细胞平均数（3．07±0．32）明显高于rhGH处理组（2．20±0．22，P〈0．05）和生理盐水对照组（0．87±0．19，P〈0．01）。结论rTMP-GH能快速、有效地促进放射损伤小鼠骨髓巨核细胞增年和向小析年矗．

Objective To investigate the in vivo effects of rTMP-GH recombinant fusion protein on thrombocytopoiesis in mice with thrombopenia inflicted by irradiation. Methods BALB/C mice weighting around 20 g were irradiated with 5 Gy of ^60Co γ-ray irradiation to generate thrombopenia. The irradiation injured mice were injected with rTMP-GH or rhGH subcutaneously at the dose of 200μg·kg^-1·d^-1 for 7 days. From the 6 th day, the platelets in blood samples from vena caudalis were counted routinely, and the pathological changes of bone marrow were determined by morphological observation. Results From the 10 th day, the levels of blood platelet in rTMP-GH treated mice were much higher than those of rhGH treatment group and normal saline （NS） control group, especially at the nadir （P 〈 0.01）. On the 22 nd day, the platelet count has recovered up to 80% of normal level in rTMP-GH treatment group, while it has just recovered up to 30% in NS control group. Morphological observation showed that there was obvious reconstruction of bone marrow in mice treated with rTMP- GH, compared with NS group. The number of megarkaryoblasts and megakaryocytes in bone marrow of rTMP-GH treated mice （3.07 ± 0.32） was much higher than those of rhGH treatment group （2.20 ± 0.22, P 〈 0.05） and NS control group （0.87 ± 0.19, P 〈 0.01 ）. Conclusions rTMP-GH has potent effects on the recovery of blood platelet by promoting megarkaryocytopoiesis in irradiation injuried mice.