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目的:观察蓖麻毒素(RT)修饰前后对小鼠肝脏毒性的影响.探讨化学修饰对改进RT抑溜作用的意义.方法:RT用 3-(2-吡啶二硫基)丙酸-羟基琥珀酰亚胺酯(SPDP)——一种异型双功能交联剂,进行修饰;生成RT的SPDP衍生物(PDP-R);在同样条件下分别测定RT和PDP-R中毒小鼠在不同剂量和时间的血清谷眈甘肽转硫酸(SGST)活性,以此为指标比较二者对肝脏的毒性差别.结果:伴随中毒剂量的增加和时间的延长二者均可使小鼠SGST活性升高,但RT组升高趋势明显高于PDP-R组.例如,当二者剂里均为12.5 ug/kg,中毒42 h时,RT组SGST活性为 PDP-R组的2.8倍(P<0.01),表明 PDP-R对小鼠的肝脏毒性明显小于RT.结论;用 SPDP修饰 RT可降低其对小鼠的肝脏毒性,这对改进RT的抑瘤作用有重要意义,因为 RT对肝脏的毒性最强,并已观察到 PDP-R对某些肿瘤的抑制作用强于RT.
Objective: To observe the effect of ricin (RT) modification on hepatotoxicity in mice and to explore the significance of chemical modification for improving RT inhibition. Methods: 3-(2-pyridyldithio)propionic acid-hydroxyl amber for RT Imidoester (SPDP), a heterobifunctional cross-linking agent, modified; SPDP derivative (PDP-R) to generate RT; RT and PDP-R poisoned mice at different doses under the same conditions And the time of serum glutathione sulfate (SGST) activity as an indicator to compare the difference in liver toxicity. Results: Both increased doses of poisoning and prolonged time can increase the activity of SGST in mice. However, the rise trend in RT group was significantly higher than that in PDP-R group. For example, when both agents were 12.5 ug/kg and 42 hours after poisoning, SGST activity in RT group was 2.8 times that of PDP-R group (P<0.01). ), indicating that the hepatotoxicity of PDP-R in mice is significantly lower than that of RT. Conclusions; STP-modified RT can reduce liver toxicity in mice, which is of great significance in improving the anti-tumor effect of RT because of liver toxicity of RT. The strongest, and has been observed that PDP-R inhibition of certain tumors stronger than RT.