脱氧胆酰酪氨酸的体外杀精和抗HIV活性研究  

In Vitro Spermicidal and Anti-HIV Effects of Deoxycholyltyosine

作　　者：李卫华[1] 刘叔文[2] 刘颖[3] 陆虹[2] 王玉柱[1] 姜世勃[2] 丁训诚[1] 

机构地区：[1]上海市计划生育科学研究所,上海200032 [2]南方医科大学药学院抗病毒研究中心,广州510515 [3]复旦大学公共卫生学院,上海200032

出　　处：《生殖与避孕》2007年第10期661-666,共6页Reproduction and Contraception

基　　金：上海市科委生物医药科研攻关课题(项目编号:054119556);教育部高等学校科技创新工程重大项目培育基金课题(项目编号:706047)

摘　　要：目的:检测自制的避孕型杀微生物剂的候选化合物脱氧胆酰酪氨酸(deoxycholyltyosine,DCT)体外杀精和抗HIV活性。方法:采用改良的Sander-Cramer方法,并用计算机辅助精子分析技术检测与DCT孵育后的各项精子运动参数。采用ELISA法检测核心抗原p24的含量,并采用染料转移法检测DCT抑制HIV诱导的细胞-细胞融合的活性。采用XTT法检测DCT对阴道上皮细胞VK2/E6E7的毒性。结果:DCT的体外杀精作用最小有效浓度(MEC)为1.0±0.2mg/ml;抑制HIV复制的半数有效浓度(IC50)为21.50±3.17μg/ml;不能阻止HIV病毒进入靶细胞;DCT对阴道上皮细胞系VK2/E6E7的细胞毒性较低。结论:DCT可作为避孕型杀微生物剂进行研发,预防意外妊娠和HIV的性传播。Objective： To test the conceptive and anti-HIV-1 activity of a new cholate derivative, deoxycholytyosine （DCT） by replacing the side chain of sodium deoxycholate （SDC） with tyrosine. Methods： DCT was tested for its spermicidal effect by a modified Sander-Cramer assay and its inhibitory activity on sperm motion by computer-aided sperm analysis. Its anti-HIV-1 activity was tested by ELISA for p24 production and a dyetransfer assay for cell-to-cell fusion assay. Its potential toxic effect on VK2/E6E7 cells was determined by XTT assay. Results： The minimum effective concentration （MEC） of DCT was 1.0 ± 0.2 mg/ml. DCT was effective in inhibiting HIV-1 replication with IC50 （the 50% inhibition concentration） of 21.50 ± 3.17 μg/ml, but could not block HIV- 1-mediated cell-to-ceU fusion. DCT had low cytotoxicity on the vaginal epithelium cell line VK2/E6E7. Conclusions： DCT has strong spermicidal effects and potent inhibitory activity on sperm motility. It also inhibits HIV-1 replication, but does not block HIV-1 entry, suggesting that it targets the late stage, rather than the early stage of the HIV-1 replication cycle. Therefore, DCT can be further developed as a contraceptive microbicide for preventing sexual transmission of HIV and unwanted pregnancy.

关 键 词：HIV/AIDS 杀精剂 杀微生物剂 脱氧胆酰酪氨酸(DCT) 

分 类 号：R96[医药卫生—药理学]