产前脂多糖暴露诱导高血压的跨代遗传
Nian Cao1,2,3, Cong Lan1,2, Caiyu Chen1,2
1Department of Cardiology, Daping Hospital (N.C., C.L., C.C., Z.X., H.L., S.Z., X.G., H.R., Z.L., S.Q., C.Y., G.W., C.H., J.Yu, C.Z.), The Third Military Medical University (Army Medical University), P.R. China.
Circulation
|August 25, 2022
概括
产前对脂聚糖 (LPS) 的不良暴露可以通过表观遗传变化导致多代高血压. 一种反应性氧物种清除剂可以防止这种跨代高血压,提供潜在的治疗策略.
科学领域:
- 环境表观遗传学
- 生殖毒理学
- 心血管疾病研究
背景情况:
- 产前不良暴露会导致后代患高血压等疾病.
- 高血压表型的跨代传播尚未得到充分理解.
研究的目的:
- 研究产前脂聚糖 (LPS) 暴露对高血压的跨代影响.
- 阐明跨代高血压的表观遗传机制.
- 探索针对氧化应激的潜在预防策略.
主要方法:
- 已经建立了大鼠LPS产前暴露的模型.
- 通过远程测量和尾巴手方法监测血压.
- 对第三代进行转录组分析 (RNA测序).
- 分析了表观遗传修饰 (H3K9me2,KDM3B) 和基因表达 (Rac1).
- 评估了醇 (ROS清除剂) 和螺旋的作用.
主要成果:
- 在产前暴露LPS诱导高血压和盐敏感性在后代到第五代.
- 患有高血压的后代表现出Rac1基因上调和激活矿物质皮质体受体信号.
- 暴露于LPS导致了氧化应激,使卵细胞中的KDM3B上调,导致遗传的H3K9me2降低和Rac1上调.
- 在第一代人中,Tempol治疗预防了高血压及其跨代遗传.
结论:
- 不良的产前暴露可以通过表观遗传机制诱导跨代高血压.
- 针对反应性氧物种提供了预防和治疗跨代高血压的潜在策略.
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