重组人白细胞介素-11对环磷酰胺致猕猴血小板减少模型的作用

The effects of rhIL-11 on hematopoietic restoration following cyclophosphamide-induced thrombocytopenia in cynomolgus monkeys

目的探讨国产重组人白细胞介素 11(rhIL 11)对化疗药物致猕猴血小板减少模型的升血小板作用。方法iv环磷酰胺诱导猕猴骨髓抑制以制备血小板减少模型 ,受试动物分成 6组 (n =4) ,分别为试验组rhIL 11[5 0、10 0及 2 0 0 μg/ (kg·d) ],阳性对照组Neumega[10 0 μg/ (kg·d) ],均连续sc 14d治疗 ,另设模型组及正常动物对照组。于化疗前及后不同时相 (d 0、3、6、9、12、15、18、2 1)观察外周血小板计数及其它血细胞计数 ;并行血小板凝集功能及骨髓涂片检查 (d 0、12、2 1)。结果受试药组血小板计数在d 12可恢复至正常 ,d 18、2 1略高于正常 ,血小板聚集率达 71.4%～ 74.6 % ,高于模型组。结论rhIL 11可以防治猕猴环磷酰胺模型的血小板下降。rhIL 11可用于因化疗所致的血小板减少症。

PurposeThe aim is to evaluate the effects of rhIL 11 made in China on hematopoietic recovery following chemotherapy induced thrombocytopenia in cynomolgus monkeys.MethodsChemotherapy induced myelosuppression of cynomolgus monkeys was made by china iv cyclophosphamide ( 30 mg/kg, qd ) for 5 days, then animals were divided 6 groups( n =4), by sc rhIL 11( 50, 100, 200 μg/kg), or Neumega (GI rhIL 11 control, 100 μg/kg) for 14 days, another normal control and model control. Blood was taken before chemothery and then at day 3, 6,9,12,15,18,21 for blood cell counts and platelet congregate test. Bone marrow was aspirated day 0, 12 and 21 for evaluation of the megakaryocyte ploidy distribution.ResultsRecovery of blood platelets was accelerated and reached normal levels by day 12, and was higher than normal day 18, day 21 sc rhIL 11 in cynomolgus moneys. Blood platelet congregated rate were 71.4%～74.6% by day 21 and higher than model control . megakaryocytes in bone marrow increased.ConclusionrhIL 11 could accelerate the recovery of peripheral blood platelets in monkeys. The function of increased platelets was normal. The results supported the clinical use of rhIL 11 as a platelet restorative agent to prevent severe thrombocytopenia following chemotherapy.