重组人白细胞介素-3的长期毒性实验研究

Experimental studies on long-term toxicity of recombinant human interleukin-3

目的 研究重组人白细胞介素 3 (Recombinanthumaninterleukin 3 ,rhIL 3 )长期应用对正常大鼠的毒性作用。方法 分设rhIL 3低剂量组 (5 μg·kg-1·d-1)、中剂量组 (10 μg·kg-1·d-1)、高剂量组 (2 5 0 μg·kg-1·d-1)及溶媒对照共 4组 ,每组 2 0只 ,每天皮下给药1次至 1、1 5、2及 3个月后 ,分别活杀 ,进行血液、尿液分析和循环免疫复合物检测 ,骨髓细胞培养 ,系统解剖及各脏器组织切片观察。结果 整个实验期动物精神食欲良好 ,无一死亡 ;血液和尿液生化、外周血象、骨髓造血细胞培养及循环免疫复合物等多项指标检测 ,各药物剂量及不同时相之间无显著差异 ;仅高剂量用药 3个月后可见骨髓组织有一定程度纤维化改变。心、肝、脾、肺、肾、脑等重要脏器组织均未见异常病理变化。结论 rhIL 3低剂量 (拟有效治疗剂量 )应用 3个月和中、高剂量应用 2个月 ,无毒副作用 ,具较好安全性 ,大剂量 (高于治疗剂量 5 0倍 )长期 (3个月 )应用可引起骨髓纤维化 。

Objective To investigate the long term toxicity of recombinant human interleukin 3 (rhIL 3) on normal rats. Methods A total of 80 rats were divided into 4 groups and treated with low (5 μg·kg -1 ·d -1 ), middle (10 μg·kg -1 ·d -1 ), high (250 μg·kg -1 ·d -1 ) dosages of rhIL 3 and menstruum for control respectively by subcutaneaus injection once a day for 1, 1.5, 2 and 3 months. After the animal were sacrificed, the blood and urine samples were tested, and circulating immunocomplex were determinated, the bone marrow cells were cultured, and the histopathological changes were observed. Results Each index in the experimental group was not different from those in the control group except the bone marrow was found in certain degree of fibrosis in the experimental group treated with high dosages of rhIL 3 for 3 months. Conclusion Although rats treated with high dosage of rhIL 3 for 3 months may cause myelofibrosis, rats with the low dosage for 3 months, middle high dosage for 2 months are well tolerated without obvious side effects.