摘要
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.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2001年第4期216-218,共3页
Chinese Journal of Hospital Pharmacy