重组人血小板生成素单次肌注给药对急性放射病猴的治疗作用  

Therapeutic Effect of Single Intramuscular Administration of Recombinant Human Thrombopoietin on Rhesus Monkeys with Acute radiation Sickness

作　　者：杨锦坤 邢爽 申星 王训 蒋瑛 张雪文 栾皓 乔子肢 戴洋洋 张恩琪 王叶梅 熊国林 余祖胤 YANG Jin-Kun;XING Shuang;SHEN Xing;WANG Xun;JIANG Ying;ZHANG Xue-Wen;LUAN Hao;QIAO Zi-Zhi;DAI Yang-Yang;ZHANG En-Qi;WANG Ye-Mei;XIONG Guo-Lin;YU Zu-Yin(Department of Experimental Hematology and Biochemistry,Beijing Key Laboratory for Radiobiology,Beijing Institute of Radiation Medicine,Beijing 100850,China)

机构地区：[1]军事科学院军事医学研究院辐射医学研究所,北京100850

出　　处：《中国实验血液学杂志》2022年第6期1887-1892,共6页Journal of Experimental Hematology

基　　金：国家科技重大专项重点项目(2018ZX09J18103-003);国家自然科学基金面上项目(81202147);军队后勤科研计划项目(AWS21J010)。

摘　　要：目的:确证重组人血小板生成素(rhTPO)对5.0 Gy^(60)Coγ射线全身照射恒河猴的治疗作用,为急性放射病的临床救治提供实验依据。方法:14只成年恒河猴均用^(60)Coγ射线源1次全身双侧照射5.0 Gy(照射量率为69.2 cGy/min)建立急性放射病模型。照射猴分为照射对照(n=5),rhTPO 5μg/kg(n=4)和rhTPO 10μg/kg(n=5)共3组,3组猴于照后2 h分别肌肉注射生理盐水0.1 ml/kg、rhTPO 5μg/kg(0.1 ml/kg)和rhTPO 10μg/kg(0.2 ml/kg)。观测受照射前及照后不同时间恒河猴的一般体征、存活情况、外周血象和血清生化等指标,比较rhTPO组与照射对照组间的差异。结果:5.0 Gy^(60)Coγ射线全身照射后猴陆续出现发热、出血、外周血全血细胞数急剧减少、血清生化指标紊乱等改变。与照射对照组相比,照射后2 h单次肌注rhTPO 5μg/kg或10μg/kg可以改善受照动物的发热、出血症状,提高受照猴外周血红细胞数、血小板数最低值,缩短血细胞减少的持续时间,并使血细胞恢复至照前水平的时间提前。血清生化检查结果显示,rhTPO可在一定程度上改善5.0 Gy全身照射引起的恒河猴血清生化指标异常。两个给药组相比,rhTPO 10μg/kg的治疗作用更佳。结论:照后2 h单次注射rhTPO 5μg/kg或10μg/kg可以减轻5.0 Gyγ射线全身照射猴多系造血损伤并促进其恢复,改善动物体征,对急性放射病有明显治疗作用。Objective:To confirm the therapeutic effect of recombinant human thrombopoietin(rhTPO)on rhesus monkeys irradiated with 5.0 Gy^(60)Coγ-ray,and provide experimental basis for clinical treatment of similar patients.Methods:Fourteen adult rhesus monkeys were irradiated with^(60)Coγ-ray on both sides at the dose of 5.0 Gy(dose rate 69.2 cGy/min)to establish the acute radiation sickness model.The monkeys were divided into irradiation group(n=5),rhTPO 5μg/kg group(n=4)and rhTPO 10μg/kg group(n=5).Two hours after irradiation,the three groups of monkeys were injected with saline 0.1 ml/kg,rhTPO 5μg/kg(0.1 ml/kg)and rhTPO 10μg/kg(0.2 ml/kg),respectively.The general signs,survival,peripheral hemogram and serum biochemistry of rhesus monkeys were observed before and after irradiation,and the differences between rhTPO group and irradiation control group were compared.Results:After total body irradiation with 5.0 Gy^(60)Coγ-ray,rhesus monkeys successively showed fever,hemorrhage,sharp decrease of whole blood cell counts in peripheral blood and disorder of serum biochemical indexes.Compared with the irradiated control group,a single intramuscular injection of rhTPO 5μg/kg or 10μg/kg 2 hours after irradiation could improve the symptoms of fever and bleeding,increase the nadir of peripheral red blood cells and platelets counts,shorten the duration of hemocytopenia,and advance the time for blood cells to return to the preirradiation level.The serum biochemical results show ed that rhT PO could improve the abnormality of serum biochemical indexes in rhesus monkeys induced by 5.0 Gy total body irradiation to some extent.Compared w ith the tw o administration groups,the therapeutic effect of rhT PO 10μg/kg w as better.Conclusion:A single injection of rhT PO 5μg/kg or 10μg/kg 2 hours after irradiation can alleviate the injury of multilineage hematopoiesis and promote the recovery in monkeys irradiated by 5.0 Gyγ-ray.It also improves animal signs and has obvious therapeutic effect on acute radiation sickness.

关 键 词：重组人血小板生成素 电离辐射 急性放射病 骨髓抑制 猕猴 

分 类 号：R818[医药卫生—放射医学]