重组人尿激酶原一般药理学研究

General Pharmacological Studies on Recombinant Human Prourokinase

试验结果显示 :尿激酶原 (prouk) 2 2 .5万IU/kg、4 5 .0万IU/kg和 90 .0万IU/kg3个组、赋形剂组和生理盐水组动物尾静脉注射给药 ,对小鼠一般行为活动表现和自发活动次数均无明显影响 .prouk 2 2 .5万IU/kg、4 5 .0万IU/kg和 90 .0万IU/kg三个组、赋形剂组和生理盐水组动物尾静脉注射给药 ,对大鼠一般行为活动表现均无明显影响 ,均能在旋转棒上协调平衡运动 .此外 ,给药后 2 0min ,三个剂量组大鼠凝血时间虽有延长 ,但与生理盐水组或赋形剂组比较无显著性差异 (P >0 .0 5 ) .prouk 11.2 5万IU/kg、2 2 .5 0万IU /kg、4 5 .0 0万IU/kg三组静脉滴注给药 ,麻醉犬的ECG、HR、呼吸均无明显改变 ,与赋形剂组比较无显著性差异 .但prouk高剂量组动物的SAP、DAP、MAP在给药 10～ 15min时短暂下降 ,这些反应在给药 30min后均恢复正常 .结果表明 ,prouk在受试剂量范围内对小鼠、大鼠精神神经活动和大鼠的凝血时间等均无明显影响 ,在 4 5 .0

Prourokinase was injected intravenously at the tail into mice and rats at doses of 225?000 IU, 450?000 IU and 900?000 IU/kg respectively. Excipient and saline were given as the control. All the animal group of mice showed that prouk had no influence on their behavior. The rats administered at different doses of prouk showed coordinate regulation on a rotating bar, none of them falling down from it. The blood clotting time of the rats at three different doses of prouk delayed in varying degrees, but there was no significant difference ( P >0.05) of blood clotting time between the prouk group and the control group. The ECG, HR and respiratory rate of the anesthetic dogs were also investigated after prouk i.v. injection at doses of 112?500 IU, 225?000 IU and 450?000 IU/kg. The results showed that prouk did not alter the above indications significantly, and that there was no marked difference between the prouk group and the excipient group. High doses of prouk induced the reduction of blood pressure (SAP, DAP and MAP) in dogs after 10～15 min of prouk administration, but the blood pressure returned to normal after 30 min. The result indicated that prouk at 450?000 IU/kg i.v. injection induced only temporary reduction of blood pressure in the anesthetic dogs.