细胞染色体P450 1A1影响肥胖引起的肺高血压
Joshua P Dignam1,2, Smriti Sharma1,3, Gregor Aitchison1
1Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
肥胖可能通过通过CYP1A1.1.增加雌激素的生产和肺代谢促进肺动脉高血压 (PAH). 用hesperetin抑制CYP1A1在与肥胖相关的PAH模型中显示出治疗潜力.
科学领域:
- 内分泌学 在内分泌学.
- 心血管研究研究心血管研究
- 代谢综合征是代谢综合征的一种.
背景情况:
- 肥胖在肺动脉高血压 (PAH) 病理生理学中的作用尚不清楚.
- 脂肪组织产生雌激素 (通过芳酶/CYP19A1),而肺部代谢它们 (通过CYP1A1).
研究的目的:
- 调查肥胖是否增强雌激素合成和新陈代谢,使人易患PAH.
- 探索CYP1A1作为肥胖PAH的潜在治疗标.
主要方法:
- 开发了一种与肥胖相关的肺高血压 (PH) 的老鼠模型,使用高脂肪饮食 (HFD) 和Sugen 5416.
- 在老鼠组织和人类PAH患者样本中量化雌激素水平和CYP1A1表达.
- 在体内和细胞培养中测试了CYP1A1抑制剂hesperetin.
主要成果:
- 肥胖大鼠和PAH患者的雌激素水平增加和肺部CYP1A1表达升高.
- 赫斯佩雷丁治疗降低了老鼠和人类细胞中的PH严重程度和CYP1A1表达.
- 脂肪组织中的CYP1A1诱导也受到hesperetin的影响.
结论:
- 增加雌激素的产生和增加的肺CYP1A1表达有助于与肥胖相关的PH.
- 对肥胖的PAH患者来说,CYP1A1抑制是一种有前途的治疗策略.
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