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依布硒啉可缓解寨卡病毒感染小鼠的睾丸病变，并阻止其性传播。

Ebselen alleviates testicular pathology in mice with Zika virus infection and prevents its sexual transmission.

机构信息

Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.

出版信息

PLoS Pathog. 2018 Feb 15;14(2):e1006854. doi: 10.1371/journal.ppat.1006854. eCollection 2018 Feb.

DOI:10.1371/journal.ppat.1006854
PMID:29447264
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5814061/
Abstract

Despite the low case fatality, Zika virus (ZIKV) infection has been associated with microcephaly in infants and Guillain-Barré syndrome. Antiviral and vaccine developments against ZIKV are still ongoing; therefore, in the meantime, preventing the disease transmission is critical. Primarily transmitted by Aedes species mosquitoes, ZIKV also can be sexually transmitted. We used AG129 mice lacking interferon-α/β and -γ receptors to study the testicular pathogenesis and sexual transmission of ZIKV. Infection of ZIKV progressively damaged mouse testes, increased testicular oxidative stress as indicated by the levels of reactive oxygen species, nitric oxide, glutathione peroxidase 4, spermatogenesis-associated-18 homolog in sperm and pro-inflammatory cytokines including IL-1β, IL-6, and G-CSF. We then evaluated the potential role of the antioxidant ebselen (EBS) in alleviating the testicular pathology with ZIKV infection. EBS treatment significantly reduced ZIKV-induced testicular oxidative stress, leucocyte infiltration and production of pro-inflammatory response. Furthermore, it improved testicular pathology and prevented the sexual transmission of ZIKV in a male-to-female mouse sperm transfer model. EBS is currently in clinical trials for various diseases. ZIKV infection could be on the list for potential use of EBS, for alleviating the testicular pathogenesis with ZIKV infection and preventing its sexual transmission.

摘要

尽管寨卡病毒（ZIKV）感染的病死率较低，但已与婴儿小头畸形和格林-巴利综合征相关。针对 ZIKV 的抗病毒和疫苗研发仍在进行中；因此，在这期间，预防疾病传播至关重要。寨卡病毒主要通过埃及伊蚊传播，也可通过性传播。我们使用缺乏干扰素-α/β和-γ受体的 AG129 小鼠来研究 ZIKV 的睾丸发病机制和性传播。ZIKV 感染逐渐损害了小鼠睾丸，导致睾丸内氧化应激增加，如活性氧、一氧化氮、谷胱甘肽过氧化物酶 4、精子中的精子发生相关 18 同源物和包括白细胞介素-1β、白细胞介素-6 和 G-CSF 在内的促炎细胞因子的水平升高。然后，我们评估了抗氧化剂 ebselen（EBS）在缓解 ZIKV 感染引起的睾丸病理变化中的潜在作用。EBS 治疗可显著减轻 ZIKV 诱导的睾丸氧化应激、白细胞浸润和促炎反应。此外，它改善了睾丸病理，并在雄性到雌性小鼠精子传递模型中防止了 ZIKV 的性传播。EBS 目前正在针对各种疾病进行临床试验。寨卡病毒感染可能会被列入 EBS 的潜在用途清单，用于缓解寨卡病毒感染引起的睾丸发病机制和防止其性传播。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f51/5814061/14a039af154c/ppat.1006854.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f51/5814061/d80933ec83e0/ppat.1006854.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f51/5814061/40377f6bef73/ppat.1006854.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f51/5814061/896bd787f264/ppat.1006854.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f51/5814061/f795a1be0cc2/ppat.1006854.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f51/5814061/1ffc225963e5/ppat.1006854.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f51/5814061/afe697ec6bf8/ppat.1006854.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f51/5814061/14a039af154c/ppat.1006854.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f51/5814061/d80933ec83e0/ppat.1006854.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f51/5814061/40377f6bef73/ppat.1006854.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f51/5814061/896bd787f264/ppat.1006854.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f51/5814061/f795a1be0cc2/ppat.1006854.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f51/5814061/1ffc225963e5/ppat.1006854.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f51/5814061/afe697ec6bf8/ppat.1006854.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f51/5814061/14a039af154c/ppat.1006854.g007.jpg

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