氨磷汀对足叶乙甙所致小鼠DNA损伤和造血损伤的预防作用研究

Effect of WR-2721 on preventing DNA damage and hematopoietic lesion of mice induced by VP-16

目的了解细胞保护剂氨磷汀(WR-2721)在拓扑异构酶Ⅱ抑制剂足叶乙甙(VP-16)对小鼠遗传损伤和造血损伤中的预防作用。方法以昆明小鼠为研究对象,采用随机数字表法将小鼠分为1、5、15 mg/kg VP-16处理组(A1、A2、A3);上述不同剂量VP-16联合200 mg/kg WR-2721处理组(B1、B2、B3);C组给予等体积生理盐水;D组给予WR-2721。通过单细胞凝胶电泳,计数拖尾细胞发生率和DNA迁移度;比较各组嗜多染红细胞(PCE)中微核(MN)比率的差异;统计各组小鼠存活率、外周血白细胞和骨髓粒-巨噬系集落形成单位(CFU-GM)。结果联合WR-2721后,MN发生率、DNA受损淋巴细胞百分率、DNA迁移度及小鼠30 d存活率、平均存活时间、外周血白细胞计数、骨髓CFU-GM计数均较单用VP-16对照组改善明显。结论WR-2721能有效降低VP-16导致的小鼠遗传损伤和骨髓造血损伤。

Objective To study the effect of WR-2721 on preventing DNA damage and hematopoietie lesion in mice treated with VP-16. Methods The Kunming strain mice were randomly divided into nine groups （n= 10 in each group） and received different doses of VP-16 alone （A1 ,A2,A3）,VP-16 combined with WR-2721 （B1 ,B2,B3）,equal volume of saline（C） and WR-2721 alone （D）. The ratios of cells with DNA damage and DNA migration were resolved by single cell gel electrophoresis. The ratios of cells with micronuclei in PCE were compared in different groups. The protective effect of WR-2721 was also tested in terms of survival rates,PWBC,CFU-GM. Results After combined with WR-2721,both the ratios for mieronuclei in PCE ,lymphoeytes with DNA damage, the DNA migration and the survival rate of 30 d,mean survival days,PWI3C and CFU-GM were ameliorated significantly. Conclusion WR-2721 could lessen effectively DNA damage and hematopoietic lesion of the mice induced by VP-16.