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联合用药与单一药物治疗对骨髓集落形成单位的辐射防护作用比较

Drug combination against single drug treatment in radiation protection of the bone marrow CFU.

作者信息

Bisht K S, Uma Devi P, Jagetia G C, Kamath G

机构信息

Department of Radiobiology, Kasturba Medical College, Manipal, India.

出版信息

Strahlenther Onkol. 1990 Aug;166(8):545-8.

PMID:2168583
Abstract

The ability of WR-2721 to protect normal tissues against ionizing radiation is limited at its maximum protective dose owing to the toxicity of the drug per se. Previous studies had indicated that MPG (2-mercaptopropionylglycine) neutralizes to some extent the toxic effects of WR-2721 without impairing the protective efficiency. The effectiveness of two doses of WR-2721 (300 mg/kg and 150 mg/kg body weight) alone or in combination with an optimal dose (20 mg/kg body weight) of MPG, on the mouse bone marrow was studied by the exogenous spleen colony assay (CFU-s) after a single whole body exposure to 4.5 Gy of gamma radiation. Both the drugs individually increased the number of spleen colonies significantly above that of the irradiated control indicating higher stem cell survival. WR-2721 treatment gave better protection than MPG. MPG was more effective when administered within 5 min before or after irradiation than when given 30 to 25 min before irradiation. The combination of WR-2721, at either dose, with 20 mg/kg MPG gave an increase in the stem cell survival as compared to the single drug treatments and this effect was synergistic at 300 mg/kg WR-2721. MPG treatment within 5 min after irradiation produced a slightly higher CFU-s count than when the drug was injected before irradiation, though the difference was not statistically significant. It is concluded that in addition to the doses of the drug, the time of administration also could influence the effect of drug combinations.

摘要

由于WR-2721本身具有毒性,其在最大保护剂量时对正常组织的电离辐射防护能力有限。先前的研究表明,MPG(2-巯基丙酰甘氨酸)在不损害保护效率的情况下,能在一定程度上中和WR-2721的毒性作用。通过外源性脾集落试验(CFU-s),研究了单次全身暴露于4.5 Gy γ射线后,两种剂量(300 mg/kg和150 mg/kg体重)的WR-2721单独使用或与最佳剂量(20 mg/kg体重)的MPG联合使用对小鼠骨髓的影响。两种药物单独使用时,脾脏集落数量均显著高于受辐照对照组,表明干细胞存活率更高。WR-2721的保护效果优于MPG。在辐照前5分钟内或辐照后给药时,MPG比在辐照前30至25分钟给药更有效。与单一药物治疗相比,两种剂量的WR-2721与20 mg/kg MPG联合使用均能提高干细胞存活率,且在300 mg/kg WR-2721时这种作用具有协同性。辐照后5分钟内给予MPG产生的CFU-s计数略高于辐照前注射该药物时,尽管差异无统计学意义。结论是,除了药物剂量外,给药时间也可能影响药物组合的效果。

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