尼马特里尔维尔通过改变PI3K/PDK1/AKT信号通路对精子功能产生有害影响
Eun-Ju Jung1, Jae-Hwan Jo2, Claudine Uwamahoro1
1Department of Animal Science and Biotechnology, Kyungpook National University, Sangju, Gyeongsangbuk-do 37224, Republic of Korea.
概括
涅玛特里尔维尔 (NMV) 通过降低精子功能和运动能力,对男性生育能力产生负面影响. 这种抗病毒药物破坏关键的信号通路,表明潜在的生殖毒性需要注意.
科学领域:
- 生殖生物学 生殖生物学
- 药理学 药理学是指药理学的学科.
- 病毒学 病毒学
背景情况:
- 尼尔马特里尔维尔 (NMV) 是SARS-CoV-2的蛋白酶抑制剂,广泛使用,但其对男性生育能力的影响尚不清楚.
- 由于其日益增长的临床应用,了解NMV对男性生殖健康的影响至关重要.
研究的目的:
- 在实验室中研究尼尔马特里尔维尔 (NMV) 对男性生殖参数的影响.
- 阐明NMV对精子功能的潜在影响背后的分子机制.
主要方法:
- 杜罗克的精子在不同度的NMV (0-100μM) 中被化.
- 评估了精子运动性,动力学,电容性,ATP水平和细胞活力.
- 西方涂抹被用于分析与PKA相关的蛋白质表达和PI3K/PDK1/AKT通路.
主要成果:
- 在剂量取决的方式,NMV显著降低了精子运动性,动力学,电容率和细胞内ATP水平.
- NMV抑制了蛋白激酶A (PKA) 的激活.
- NMV增加了PI3K,PDK1,AKT及其酸化形式的表达,表明途径失调.
结论:
- 尼马特里尔维尔对精子功能产生有害影响,可能通过破坏PI3K/PDK1/AKT通路,导致PKA失活.
- 在Nirmatrelvir的使用过程中,应考虑男性生殖毒性.
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