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抗菌肽Nisin的避孕效果:体外和体内研究

Contraceptive efficacy of antimicrobial peptide Nisin: in vitro and in vivo studies.

作者信息

Aranha Clara, Gupta Sadhana, Reddy K V R

机构信息

Department of Immunology, National Institute for Research in Reproductive Health, J.M. Street, Parel, Mumbai 400012, India.

出版信息

Contraception. 2004 Apr;69(4):333-8. doi: 10.1016/j.contraception.2003.11.002.

DOI:10.1016/j.contraception.2003.11.002
PMID:15033410
Abstract

Sexually transmitted infections and unplanned pregnancies present a great risk to the reproductive health of women. Therefore, female-controlled vaginal products directed toward disease prevention and contraception are needed urgently. In the present study, efforts were made to evaluate the contraceptive potential of Nisin. The effect of Nisin on sperm motility was assessed under in vitro and in vivo conditions. The results showed that sperm motility was completely inhibited with Nisin. The minimum effective concentration of Nisin required to immobilize sperm (80-100 x 10(6)) in vitro within 20 s was found to be 50 microg in rat, 200 microg in rabbit and 300-400 microg in monkey and human. The effect on sperm motility was observed to be dose- and time-dependent. Intravaginal administration of Nisin (200 microg) before mating during proestrus-estrous transition phase caused complete arrest of sperm motility and blockage of conception. Subacute toxicity studies in rats indicated that, repetitive intravaginal application of Nisin at the dose of 200 microg for 14 consecutive days induced no abnormalities either in the length of estrous cycle or in the morphology of vaginal epithelial cells. No histopathological abnormalities in vaginal tissue or any change in blood and serum biochemical profiles were observed. Furthermore, no adverse effects were observed on subsequent reproductive performance, neonate survival and development of pups. It is suggested that Nisin, with its antibacterial and spermicidal activities, could be developed as a potent vaginal contraceptive for future use in humans.

摘要

性传播感染和意外怀孕对女性生殖健康构成巨大风险。因此,迫切需要女性控制的用于疾病预防和避孕的阴道产品。在本研究中,我们努力评估乳酸链球菌素的避孕潜力。在体外和体内条件下评估了乳酸链球菌素对精子活力的影响。结果表明,乳酸链球菌素可完全抑制精子活力。发现在体外20秒内使大鼠(80 - 100×10⁶)、兔子200微克、猴子和人类300 - 400微克精子固定所需的乳酸链球菌素的最低有效浓度。观察到对精子活力的影响呈剂量和时间依赖性。在发情前期 - 发情过渡期交配前经阴道给予乳酸链球菌素(200微克)可导致精子活力完全停止并阻止受孕。大鼠的亚急性毒性研究表明,连续14天以200微克的剂量重复经阴道应用乳酸链球菌素,在发情周期长度或阴道上皮细胞形态方面均未诱发异常。未观察到阴道组织的组织病理学异常或血液和血清生化指标有任何变化。此外,对随后的生殖性能、新生仔鼠存活和发育未观察到不良影响。建议具有抗菌和杀精活性的乳酸链球菌素可开发成为一种有效的阴道避孕药,供未来人类使用。

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