重组L-门冬酰胺酶前体脂质体与重组L-门冬酰胺酶对小鼠毒性作用比较

The Toxicity Effect of Recombinant L-Asparaginase Proliposome and Recombinant L-Asparaginase in Mice

为了考查L 门冬酰胺酶 (L Asparaginase ,L ASNase)前体脂质体 (Proliposomes) (L ASNasePL)与L ASNase的急性毒性及对外周血中白细胞总数及血小板数的作用。脂质体组小鼠静脉注射给药 (L ASNasePL) ,给药剂量为给以最大药物浓度 (4 0 0 0KU/m1) ,最大静脉注射体积 (0 5m1/ 2 0 g) ;L ASNase组给药体积为 0 4ml/ 2 0 g ,给药一次 ,给药后每天观察记录小鼠活动、死亡情况 ,共观察 14d。结果L ASNasePL的毒性与L AS Nase相比明显降低 ,其小鼠iv的L ASNasePL的最大耐受量为 10 0× 10 5KU/kg ,相当于每日人临床拟用剂量的5 0 0 0倍。对正常小鼠体重、外周血中白细胞总数及血小板数的影响 :L ASNase高剂量组 (10 0 0KU/kg)有显著降低小鼠外周血中白细胞总数及血小板数的作用 (P <0 0 5 ) ,而L ASNasePL对小鼠外周血中白细胞总数及血小板数无明显影响。L ASNasePL组及L ASNase组对小鼠体重增长均无明显影响。说明L 门冬酰胺酶前体脂质体急性毒性明显小于L 门冬酰胺酶 ,L

To explore the acute toxicity of recombinant L asparaginase proliposome (L ASNasePL) and recombinant L asparaginase (L ASNase) and the influence on peripheral leucocyte count and platelets The most concentration of L ASNasePL (4000 KU/m1) and most volume of iv (0 5 ml/20 g ) was given to L ASNasePL group mice one time for 14 days Data was calculated using Bliss method The iv LD 50 of L ASNase was 94 104 ×10 4 KU/kg The max tolerance dose of L ASNasePL was 10 0×10 5 KU/kg That was equal to 5000 times of daily clinic dosage The effect of L ASNasePL on peripheral leucocyte count and platelets was significantly ( P <0 05) lower than that of L ASNase compared with control The influence of L ASNasePL and L ASNase on body weight of mice was not apparent The toxicity of L ASNasePL was distinctively lower than that of L ASNase in mice