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抗逆转录病毒药物对人精子体外不良影响的评估。

In vitro assessment of the adverse effects of antiretroviral drugs on the human male gamete.

机构信息

Université de Toulouse, UPS, Groupe de Recherche en Fertilité Humaine (EA 3694, Human Fertility Research Group), Toulouse, France.

出版信息

Toxicol In Vitro. 2011 Mar;25(2):485-91. doi: 10.1016/j.tiv.2010.11.020. Epub 2010 Dec 2.

DOI:10.1016/j.tiv.2010.11.020
PMID:21130153
Abstract

This study was designed to investigate the in vitro effects of didanosine, zidovudine, saquinavir and indinavir, commonly used in highly active antiretroviral therapy, on human sperm fertility parameters. Thirty semen samples from healthy men were collected and prepared by gradient density method. Aliquots of 90% fractions with >80% motile spermatozoa were incubated for 1, 3, and 6h with different concentrations of the antiretroviral drugs (20, 40, and 80 μg/ml). Sperm motility was evaluated by computer assisted sperm analysis system. Sperm mitochondrial potential was evaluated using 3,3'-dihexyloxacarbocyanine iodide (DIOC(6)) and the acrosome reaction was examined using pisum sativum agglutinin method. A dose-dependent decrease in sperm motility was observed with saquinavir. Saquinavir also induced a significant time and dose-dependent decrease in mitochondrial potential and an increase in spontaneous acrosome reaction. These findings indicate that, in vitro, higher doses of saquinavir have adverse effects on sperm motility, mitochondrial potential and acrosome reaction.

摘要

本研究旨在探讨临床上常用于高效抗逆转录病毒治疗的药物(如:去羟肌苷、齐多夫定、沙奎那韦和茚地那韦)对人精子生育参数的体外影响。研究人员收集了 30 名健康男性的精液样本,并采用梯度密度法进行处理。将 >80%活动精子的 90%部分等分试样与不同浓度的抗病毒药物(20、40 和 80μg/ml)孵育 1、3 和 6 小时。采用计算机辅助精子分析系统评估精子的运动能力。使用 3,3'-二己氧基羰花青碘化物(DIOC(6))评估精子线粒体的潜能,采用豌豆凝集素法检测顶体反应。结果显示,沙奎那韦可导致精子运动能力呈剂量依赖性下降。此外,沙奎那韦还可导致线粒体潜能显著地、时间和剂量依赖性下降,以及自发性顶体反应增加。这些发现表明,体外条件下,较高剂量的沙奎那韦对精子运动能力、线粒体潜能和顶体反应具有不良影响。

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