修饰蓖麻毒素减轻其对小鼠肝毒性的研究  

Effect of modified ricin on the reduction of hepatotoxicity in mice

作　　者：李文丽[1] 海春旭[1] 赵英[1] 梁欣[1] 王文学[1] 

机构地区：[1]第四军医大学预防医学系毒理学教研室,西安710032

出　　处：《中华劳动卫生职业病杂志》2003年第3期209-211,共3页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：国家青年自然科学基金资助项目 (3 95 0 0 12 2 )

摘　　要：目的　探讨化学修饰后的蓖麻毒素 (RT)对小鼠肝脏毒性及其抗癌作用的变化。方法　测定RT及其修饰物N [3 (2 吡啶二硫基 )丙酰基 ]蓖麻毒素 (RT PDP)染毒小鼠血清谷胱甘肽转硫酶 (GST)活力、肝组织谷胱甘肽 (GSH)含量 ,电镜下观察染毒小鼠肝脏的病理改变。结果　随着RT及RT PDP染毒剂量的增加 ,小鼠血清GST活力随之增加 ,且RT组小鼠血清GST活力高于RT PDP组。当染毒剂量均为 12 .5、15 .0 μg/kg时 ,RT组小鼠血清GST活力 [(93.6 5± 12 .30 )、(15 3.71±2 6 .6 4 )IU/L]明显高于RT PDP组 [(6 2 .97± 11.2 2 )、(78.2 0± 15 .71)IU/L],差异有显著性 (P <0 .0 5 ) ;RT和RT PDP各剂量染毒组小鼠肝组织GSH含量均随染毒剂量增加而下降 ,当染毒剂量为 2 .5、5 .0、7.5、10 .0、15 .0 μg/kg时 ,RT组小鼠肝组织匀浆中GSH含量分别为 (3.5 3± 0 .95 )、(2 .12± 0 .5 4 )、(1.82±0 .71)、(1.5 2± 0 .34)、(0 .81± 0 .36 ) μmol/L ,RT PDP组小鼠肝组织匀浆中GSH含量分别为 (6 .34±1.4 3)、(4.14± 1.82 )、(3.5 4± 0 .6 4 )、(2 .73± 1.82 )、(1.82± 0 .6 2 ) μmol/L ,RT PDP组仍明显高于RT组 ,差异均有显著性 (P <0 .0 1) ;电镜观察显示 ,RT对小鼠肝细胞的损伤大于RT PDP。Objective To observe the significance of ricin(RT) with chemical nidification to reduce the hepatotoxicity in mice and its anticancer effect. Methods Mice were exposed to RT and RT-PDP[ricin chemically modified by N-succinimidyl 3-(2-pyridyldithio)-propionate,(SPDP)] respectively,and their serum activity of glutathione-S-transferase(GST) and liver glutathione(GSH) content were determined.The ultramicro-structure under electron microscope was also observed. Results The GST activity increased with doses,and the increase in ricin group was higher than that in RT-PDP group;the activities of GST in RT group at 12.5,15.0 μg/kg[(93.65± 12.30) ,(153.71±26.64)IU/L respectively] were higher than those in RT-PDP group[(62.97±11.22), (78.20 ± 15.71) IU/L]( P <0.05).The contents of GSH were decreased with doses;but the contents of GSH in RT-PDP group at 2.5,5.0,7.5,10.0,15.0 μg/kg[(6.34±1.43),(4.14± 1.82) ,(3.54±0.64),(2.73± 1.82) , (1.82 ±0.62)μmol/L respectively] were still higher than those in RT group[(3.53±0.95),(2.12± 0.54) , (1.82 ±0.71),(1.52±0.34),(0.81±0.36)μmol/L]( P <0.01).Electron microscopic examination showed that the injury of liver cells in RT group was more severe than that in RT-PDP group. Conclusion The hepatotoxicity of ricin in mice may be reduced by chemical modification.

关 键 词：修饰蓖麻毒素 抗癌药物 肝毒性 谷胱甘肽转硫酶 谷胱甘肽 

分 类 号：R99[医药卫生—毒理学]