重组L-门冬酰胺酶前体脂质体对急性淋巴白血病小鼠的治疗作用和毒性考察

Effect of recombinant -L-asparaginase proliposome on the acute lymphatic leukaemia and the toxicity in mice

目的 :考察重组L 门冬酰胺酶前体脂质体 (L ASNasePL)与重组L 门冬酰胺酶 (L Asparaginase ,L ASNase)对移植性小鼠急性淋巴白血病的作用 ,及相关急性毒性。方法 :采用DBA/2小鼠L12 10 腹水瘤模型 ,L ASNasePL组和L ASNase组小鼠每天腹腔注射一次 ,连续 10d。另设L ASNasePL组小鼠静脉注射给药 ,给以最大药物浓度 (4 0 0 0kU·m1-1) ,最大静脉注射体积 [0 .5m1·(2 0g) -1];L ASNase组给药体积为 0 .4ml·(2 0g) -1,给药一次后每天记录小鼠情况 ,共 14d。用Bliss法计算LD50 。结果 :L ASNasePL及L ASNase皆能显著延长L12 10 的小鼠存活天数 (P <0 .0 1) ,L ASNasePL对L12 10 移植小鼠 ,生命延长率最高达 184.7%。L ASNase组生命延长率最高为 132 .9%。L ASNasePL的毒性与L ASNase相比明显降低 ,其小鼠静注的L ASNasePL的最大耐受量为 10 .0× 10 5kU·kg-1。L ASNasePL及L ASNase对小鼠体重无明显影响。结论 :高、中剂量L ASNasePL与同剂量的L ASNase相比 ,均显著延长L12 10 小鼠的存活天数 (P <0 .0 5 )。L ASNasePL急性毒性明显小于L AS Nase。

OBJECTIVE To examine the effect of L Asparaginase proliposomes ( L ASNasePL) and L Asparaginase (L ASNase) on acute lymphatic leukaemia in mice, and to explore the acute toxicity of them. METHODS The dose of L ASNasePL and L ASNase group mice was given ip one time every day for 10 days adopting L 1210 acute tumor model. Saline and doxorubicin used as negative and positive control. The most concentration of L ASNasePL (4000kU·m1 -1 ) and most volume of iv [ 0.5 ml·(20 g) -1 ] was given to L ASNasePL group mice one time for 14 days. Data was calculated using Bliss method. RESULTS L ASNasePL and L ASNase could extend acute lymphatic leukaemia mice survival time significantly( P < 0.01 ). The life lengthen ratio of L ASNasePL was the highest to 184.7% in L 1210 group, and that of L ASNase was the highest to 132.9% in L 1210 group. The iv LD 50 of recombinant L asparaginase (L ASNase) was 94.104 ×10 4kU·kg -1 . The max tolerance dose of L ASNasePL was 10.0 ×10 5 kU·kg -1 . The influence of L ASNasePL and L ASNase on body weight of mice was not apparent. CONCLUSIONS Compared with the same dose of L ASNase, the high and middle dose L ASNasePL extend survival time of L 1210 ( P < 0.05 ). The toxicity of recombinant L asparaginase proliposome (L ASNasePL) was distinctively lower than that of L asparaginase (L ASNase) in mice.