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治疗子宫内膜异位症的新型药物及其在小鼠模型中的治疗效果

Novel Medicine for Endometriosis and Its Therapeutic Effect in a Mouse Model.

作者信息

Kim Young Sang, Kim Yu Jin, Kim Myung Joo, Lee Sang Jin, Kwon Hwang, Lee Jae Ho

机构信息

CHA Fertility Center Seoul Station, Seoul 04637, Korea.

Laboratory of Reproductive and Molecular Medicine, CHA Fertility Center Seoul Station, Seoul 04637, Korea.

出版信息

Biomedicines. 2020 Dec 16;8(12):619. doi: 10.3390/biomedicines8120619.

Abstract

Current therapeutic medicines for endometriosis cannot be administered during assisted reproductive technology (ART) because they have bad effects during pregnancy. In this study, we created an animal model of endometriosis and evaluated the therapeutic effect of progestin (Dienogest), dopamine agonist (Cabergoline), and their combination (Dienogest + Cabergoline). We established a mouse model mimicking human endometriosis. The mice with endometriosis were then treated with a single drug (Dienogest or Cabergoline) or both drugs (Dienogest + Cabergoline) for 14 days. An immunohistological study was then performed to analyze inflammatory lesions in the recipient mice. Real-time polymerase chain reaction (RT-PCR) and Western blotting were also performed to determine the levels of genes and proteins in inflammatory lesions to assess the recovery of endometriosis. Histologic staining showed that all medication groups showed a clear decrease in the inflammatory phenotype in the uterus, peritoneum, and intestine. Gene and protein expression analysis showed a therapeutic effect in all medication groups. In conclusion, Cabergoline had a therapeutic effect similar to that of Dienogest and could be used as an alternative to Dienogest during ART for patients with infertility; compared to the individual drugs, the combination treatment has a synergistic effect on endometriosis.

摘要

目前用于治疗子宫内膜异位症的药物在辅助生殖技术(ART)期间不能使用,因为它们在怀孕期间有不良影响。在本研究中,我们创建了子宫内膜异位症动物模型,并评估了孕激素(地诺孕素)、多巴胺激动剂(卡麦角林)及其组合(地诺孕素+卡麦角林)的治疗效果。我们建立了一种模拟人类子宫内膜异位症的小鼠模型。然后,对患有子宫内膜异位症的小鼠用单一药物(地诺孕素或卡麦角林)或两种药物(地诺孕素+卡麦角林)治疗14天。然后进行免疫组织学研究,分析受体小鼠的炎症病变。还进行了实时聚合酶链反应(RT-PCR)和蛋白质印迹分析,以确定炎症病变中基因和蛋白质的水平,评估子宫内膜异位症的恢复情况。组织学染色显示,所有用药组子宫、腹膜和肠道的炎症表型均明显减轻。基因和蛋白质表达分析显示所有用药组均有治疗效果。总之,卡麦角林具有与地诺孕素相似的治疗效果,可作为ART期间不孕患者地诺孕素的替代品;与单一药物相比,联合治疗对子宫内膜异位症有协同作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7911/7766695/e12deeeccef7/biomedicines-08-00619-g001.jpg

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