修饰蓖麻毒素减轻其对小鼠肝毒性的研究

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。结论　化学修饰蓖麻毒素可

Effect of modified ricin on the reduction of hepatotoxicity in mice

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 micro g/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 micro g/kg (6.34 +/- 1.43), (4.14 +/- 1.82), (3.54 +/- 0.64), (2.73 +/- 1.82), (1.82 +/- 0.62) micro mol/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) micro mol/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.