摘要
目的 :观察重组人白介素 - 11(rh IL - 11)对猕猴的长期毒性。 方法 :18只猕猴分别按体质量随机分为 4组。高剂量组6只 ,余均为 4只。低、中、高剂量分别为 0 .1、0 .3和 1.0 mg/kg。每天 sc给药 1次 ,连续 90 d。停药观察 30 d。观察症状和检测项目有 :一般状况、心电图、血液学及生化指标、尿液、免疫、骨髓、脏器质量、组织学检查。结果 :所有给药组猕猴食量明显减少 ,体质量有所减轻 ,并有短暂性发热。低剂量组有 1只猕猴肢体活动受限 ,震颤。高剂量组 1只猕猴出现呕吐 ,1只死亡。给药组 RBC、Hb、Hct、MCV、MCH和 MCHC均明显降低 ,Plat则明显增高。 AL T、AST、L DH活性明显下降 ,TP和 Alb含量明显下降 ,AL P活性明显升高。给药 90 d各给药组猕猴均出现抗 IL - 11抗体 ,免疫复合物也明显增高。高、中剂量组骨髓有核细胞增生明显活跃。给药组心、肝的绝对质量有增大的趋势 ,相对质量明显增大。给药 90 d时 ,给药组猕猴肝、肾出现明显的细胞变性 ,中、高剂量组重于低剂量组。停药后 30 d上述变化均趋向恢复。 结论 :rh IL - 11对猕猴的毒性靶器官及系统有 :血液系统、肝脏、肾脏、免疫系统、骨髓。其毒性损害均为可逆性。 rh IL - 11对猕猴的 3个月长期毒性安全剂量为每次 0 .1m g/kg。
Objective:To investigate the long term toxicity of recombinant human interleukin 11(rhIL 11) in cynomolgus. Methods: Eighteen cynomolgus were randomized into 4 groups: control group(2/sex), low dose group(2/sex), medium dose group(2/sex), and high dose group(3/sex). The drug groups were sc adminstered 0.1, 0.3 and 1.0 mg/kg of rhIL 11 for 90 days with a 30 day recovery period. The clinical signs were observed, electrocardiogram, hematological, biochemical, urinary and immunological parameters were measured, organ masses were weighed, bone marrow and pathological histology were observed. Results: The food consumption, body mass of the drug groups were decreased, the body temperature was increased transiently. One of the low dose group showed restricted movements and tremors. One of the high dose group vomited and another died. Reduced red blood cell(RBC) count, hemoglobin(Hb) concentration, hematocrit(Hct), mean corpuscular volume(MCV), mean corpuscular hemoglobin(MCH), and mean corpuscular hemoglobin concentration(MCHC), dose related increase of platelet(Plat) counts were present in drug groups. Biochemical examinations revealed dose related decreases in serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), lactate dehydrogenase(LDH), total proteins(TP) and albumin(Alb) increases in serum alkaline phosphatase(ALP) levels. Positive antibody responses were seen and circulatory immune complex(CIC) was significantly increased in all drug groups. Hypertropy of marrow megakaryocyocytes was noted in the medium and high dose groups. The heart and liver masses were slightly increased in all treatment groups. Treatment related microscopic findings included dose related degeneration in the liver and the kidney. The adverse effects were reversed by the end of the recovery period. Conclusion: The target organs and systems are blood, liver, kidney, immmue system and bone marrow. The toxicity injuries were reversible and the no toxic effect level is 0.1 mg/kg. [
出处
《第二军医大学学报》
CAS
CSCD
北大核心
2001年第4期360-363,共4页
Academic Journal of Second Military Medical University
