Achilles Sharon L, Shete Priya B, Whaley Kevin J, Moench Thomas R, Cone Richard A
The Johns Hopkins University, Baltimore, Maryland, USA.
Sex Transm Dis. 2002 Nov;29(11):655-64. doi: 10.1097/00007435-200211000-00007.
Microbicides are being developed for woman-controlled protection against sexually transmitted diseases (STDs).
The goal of the study was to test candidate microbicides in a mouse model for preventing vaginal transmission of and for acute toxicity to columnar epithelium.
Progestin-sensitized CF-1 mice were treated vaginally with 50 microl of microbicide, followed either by vaginal inoculation with 10 ID(50) of serovar D or by examination of the epithelial surface for acute toxicity with a viability stain (ethidium homodimer-1).
Nonoxynol-9 (N9), sodium dodecyl sulfate (SDS), chlorhexidine digluconate, and BufferGel all provided significant though incomplete protection against vaginal transmission. Other candidates, all of which were effective in vitro, provided no vaginal protection: kappa-carrageenan, dextran sulfate, polystyrene sulfonate, Concanavalin A, wheat germ agglutinin, and agglutinin. The surface-active agents (N9, SDS, and chlorhexidine) caused significant acute epithelial toxicity: 3 days after chlorhexidine exposure, mice also had vaginal friability and markedly increased susceptibility to. BufferGel was the only candidate tested that was both protective and relatively nontoxic.
Microbicides can provide vaginal protection against in highly susceptible progestin-sensitized mice. Since N9 does not inactivate, it likely protects by killing target cells in the vagina. Despite the ability to both potently inactivate and kill target cells, two surface-active agents, SDS and chlorhexidine, failed to provide complete protection, a circumstance which emphasizes the importance of distributing microbicides to all susceptible surfaces.
正在研发由女性控制的预防性传播疾病（STD）的杀微生物剂。
本研究的目的是在小鼠模型中测试候选杀微生物剂对柱状上皮的阴道传播预防作用及急性毒性。
用50微升杀微生物剂经阴道处理孕激素致敏的CF-1小鼠，随后进行阴道接种10个血清型D的半数感染剂量（ID50），或用活性染色剂（乙锭同二聚体-1）检查上皮表面的急性毒性。
壬苯醇醚-9（N9）、十二烷基硫酸钠（SDS）、葡萄糖酸洗必泰及缓冲凝胶均提供了显著但不完全的阴道传播预防作用。其他在体外有效的候选物未提供阴道保护作用：κ-角叉菜胶、硫酸葡聚糖、聚苯乙烯磺酸盐、伴刀豆球蛋白A、麦胚凝集素及凝集素。表面活性剂（N9、SDS及洗必泰）引起显著的急性上皮毒性：洗必泰暴露3天后，小鼠还出现阴道脆性增加及对……的易感性显著增加。缓冲凝胶是所测试的唯一一种既有保护作用又相对无毒的候选物。
杀微生物剂可在高度易感的孕激素致敏小鼠中提供阴道保护作用。由于N9不能使……失活，它可能通过杀死阴道中的靶细胞起到保护作用。尽管有强大的使靶细胞失活和杀死靶细胞的能力，但两种表面活性剂SDS和洗必泰未能提供完全保护，这种情况强调了将杀微生物剂分布到所有易感表面的重要性。
