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长春碱纳米粒的细胞毒性和急性毒性研究
刘玉梅1,2, 欧阳五庆1, 张自强2
1.西北农林科技大学 动物医学院;2.河南科技大学 动物科技学院
摘要:
【目的】 探讨长春碱聚氰基丙烯酸正丁酯纳米粒(VLB-PBCA-NP)对正常细胞的毒性及其急性毒性。【方法】 采用MTT法并结合形态学观察,比较了VLB-PBCA-NP和VLB原料药对原代大鼠星形胶质细胞和小鼠成纤维细胞L929的毒性;用相同剂量的VLB-PBCA-NP和VLB原料药溶液对小鼠进行尾静脉注射,每日观察小鼠死亡情况,并计算半数致死量(LD50)。【结果】 在质量浓度为0.5~50 ng/mL时,VLB-PBCA-NP和VLB原料药对星形胶质细胞增殖抑制率的影响无显著性差异,当质量浓度达到500 和5 000 ng/mL时,VLB-PBCA-NP对大鼠星形胶质细胞的毒性显著低于VLB原料药(P<0.05)。5 000 ng/mL的VLB-PBCA-NP对小鼠成纤维细胞L929的毒性为3级,极显著降低了VLB原料药的毒性(P<0.01)。VLB-PBCA-NP和VLB原料药的LD50分别为26.38 和22.7 mg/kg,前者较后者提高了16.21%。【结论】 VLB-PBCA-NP对小鼠的急性毒性和对非肿瘤细胞的毒性均显著低于VLB原料药。
关键词:  长春碱  纳米粒  L929细胞  星形胶质细胞  半数致死量
DOI:
分类号:
基金项目:国家科技支撑计划项目(2006BAD04A11)
Cytotoxicity and acute toxicity study on vinblastine (VLB) nanoparticles
Abstract:
【Objective】 The aim of this study was to investigate toxicity of VLB poly(buty1 cyanoacrylate) nanoparticles ( PBCA-NP).【Method】 Difference between VLB-PBCA-NP and crude VLB on the growth of L929 and rat astrocyte was measured by MTT assay and morphology method.In addition,after the same dose of VLB-PBCA-NP and crude VLB solution were injected into mice tail vein,50% lethal dose of (LD50) was counted.【Results】 The results indicated that there was no significant difference on the effect of rat astrocyte growth between 0.5-50 ng/mL VLB-PBCA-NP and crude VLB solution,but 500 and 5000 ng/mL VLB-PBCA-NP significantly degraded cytotoxicity (P<0.05).5 000 ng/mL VLB-PBCA-NP belonged to toxicity grade 3 on L929 fibroblasts growth,and very significantly degraded crude VLB toxicity.The LD50 of VLB-PBCA-NP and crude VLB solution was respectively 26.38 and 22.7 mg/kg.The LD50 of VLB-PBCA-NP increased by 16.21% compared with crude VLB solution.【Conclusion】 VLB-PBCA-NP degraded acute toxicity and nontumorous cells toxicity of crude VLB.
Key words:  vinblastine (VLB)  nanoparticle  L929 cell  astrocyte  LD50