重组人组织型纤溶酶原激活剂缺失变体对猕猴的长期毒性研究

Studies on the long-term toxicities of reteplase in macaca fasicular

目的 观察重组人组织型纤溶酶原激活剂缺失变体(reteplase,Ret)的长期毒性作用。 方法 连续 14d给猕猴静脉注射不同剂量Ret。结果 Ret 8 0MIU·kg-1对猕猴不表现任何毒性作用 ,Ret 2 5 0、80 0MIU·kg-1组的血液RBC、HGB及HCT均降低 ,部分猕猴粪便隐血试验阳性 ,血液生化学检查有TP下降 ,但这些指标在停药 14d时基本恢复正常。另外 ,所有给药猕猴出血时间均延长 ,但脏器系数和病理学未见有毒性变化。结论 Ret静脉注射 8 0MIU·kg-1是安全剂量 ,2 5 0、80 0MIU·kg-1两个剂量有一定的毒性反应 ,主要表现为贫血和出血 ,停药后毒性可以恢复。

AIM To observe the long-term toxicities of reteplase(Ret). METHODS Rat was administrated by injection of vein on 14 consecutive days to macaca fasicular. RESULTS Ret 8.0 MIU·kg -1 to macaca fasicular did not show any toxicity. In 25.0 MIU·kg -1 and 80.0 MIU·kg -1 of doses, RBC, HGB and HCT of blood have significantly decreased. Feces of hidden blood test also showed positive response in some animals, meanwhile, Ret could reduce the content of plasma total protein. But these changes could have recovery in restoration period. In addition, in 8.0?25.0?80.0 MIU·kg -1 doses, Ret could significantly lengthen bleeding time and clotting time. The obvious toxic changes of coefficient and pathology in Ret 8.0?25.0?80.0 MIU·kg -1 groups were not found. CONCLUSION 8.0 MIU·kg -1 is a safety dosage by injection of vein. 25.0,80.0 MIU·kg -1 doses have certain toxic actions, such as anemia and bleeding, but these toxic effects were reversible.