左旋二脱水伊地醇双甲磺酸酯及其代谢物对HL-60细胞株增殖的影响  

Effect of DMDAI-L alone and DMDAI-L metabolite after incubated with the liver microsome on HL-60 cells

作　　者：曹斌[1] 刘元[1] 杨小叶[2] 杨斌[2] 

机构地区：[1]广西中医药研究院,广西南宁530022 [2]广西医科大学,广西南宁530021

出　　处：《华西药学杂志》2014年第5期545-547,共3页West China Journal of Pharmaceutical Sciences

基　　金：广西自然科学基金项目应用基础研究专项基金资助(批准号:0991013)

摘　　要：目的评价左旋二脱水伊地醇双甲磺酸酯（DMDAI-L）及其经肝微粒体体外孵育后的代谢物对白血病HL-60细胞增殖的影响。方法采用大鼠肝微粒体体外孵育的方法孵育DMDAI-L,用中性红染色细胞活性试验法测定DMDAI-L原药及其经肝微粒体孵育后的代谢物对HL-60细胞增殖的影响。结果各浓度药物作用HL-60细胞24 h后,代谢物组（40～80μg·mL^-1）及原药组（20～80μg·mL^-1）与空白对照组比较有统计学意义（P〈0.01）;与原药相比,代谢物对HL-60细胞增殖抑制作用减弱,原药作用于HL-60细胞24 h的IC50为59.07μg·mL^-1,而其经孵育后代谢物的IC50为81.29μg·mL^-1。结论 DMDAI-L经肝微粒体孵育后代谢物的抗肿瘤活性减弱,减弱作用与肝微粒体介导的代谢有关。OBJECTIVE To compare the effect of DMDAI - L after incubated with the liver microsome and DMDAI - L alone on human myeloid leukemia HL - 60 cells. METHODS The rat liver mierosome .was incubated in vitro to metabolize DMDAI - L, and the proliferation inhibitory effect of DMDAI - L alone and after incubated with the liver microsome were detected on HL - 60 cells by neutral red assay. RESULTS The different concentrations of DMDAI - L （ 20 - 80 μg· mL ^- 1 ） and its metabolites （ 40 - 80 μg· mL ^- 1 ） had significant difference to the blank control group after treatment for 24 hours（ P 〈 0.01 ）. The effect of DMDAI -L after incubated with the rat liver microsome was lower than DMDAI - L alone on the proliferation inhibitory in HL - 60 cells. The IC_50 values after treat- ment with DMDAI- L to HL-60 cells for 24 hours was 59.07 μg·mL^-1, compared with 81.29 μgμmL^-1 for it after incubated with the rat liver microsome. CONCLUSION The activity of DMDAI - L after incubated with the rat liver mircosome is lower than DMDAI -L, which may be related to the metabolization of the rat microsome.

关 键 词：左旋二脱水伊地醇双甲磺酸酯(DMDAI-L) 体外代谢 HL-60细胞 增值抑制作用 

分 类 号：R96[医药卫生—药理学]