CAJ | 학술논문

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L1210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（4000kU·m1-1）,最大静脉注射体积[0.5m1·(20g)-1]；L-ASNase组给药体积为0.4ml·(20g)-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L1210的小鼠存活天数（P＜0.01）,L-ASNasePL对L1210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10.0×105kU·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L1210小鼠的存活天数（P＜0.05）。L-ASNasePL急性毒性明显小于L-ASNase。
목적：고찰중조L-문동선알매전체지질체(L-ASNasePL)여중조L-문동선알매（L-Asparaginase,L-ASNase）대이식성소서급성림파백혈병적작용，급상관급성독성。방법：채용DBA／2소서L1210복수류모형,L-ASNasePL조화L-ASNase조소서매천복강주사일차,련속10d。령설L-ASNasePL조소서정맥주사급약,급이최대약물농도（4000kU·m1-1）,최대정맥주사체적[0.5m1·(20g)-1]；L-ASNase조급약체적위0.4ml·(20g)-1，급약일차후매천기록소서정황,공14d。용Bliss법계산LD50。결과：L-ASNasePL급L-ASNase개능현저연장L1210적소서존활천수（P＜0.01）,L-ASNasePL대L1210이식소서，생명연장솔최고체184.7%。L-ASNase조생명연장솔최고위132.9%。L-ASNasePL적독성여L-ASNase상비명현강저，기소서정주적L-ASNasePL적최대내수량위10.0×105kU·kg-1。L-ASNasePL급L-ASNase대소서체중무명현영향。결론：고、중제량L-ASNasePL여동제량적L-ASNase상비,균현저연장L1210소서적존활천수（P＜0.05）。L-ASNasePL급성독성명현소우L-ASNase。
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 L1210 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 L1210 group, and that of L-ASNase was the highest to 132.9% in L1210 group. The iv LD50 of recombinant-L-asparaginase (L-ASNase) was 94.104×104kU·kg-1. The max tolerance dose of L-ASNasePL was 10.0×105 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 L1210（P＜0.05）. The toxicity of recombinant -L-asparaginase proliposome (L-ASNasePL) was distinctively lower than that of L-asparaginase (L-ASNase) in mice.