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阿塔萨纳维尔诱导的非结合性高 bilirubinemia 在实验性人类内毒素症期间防止血管高活性
Mirrin J Dorresteijn1,2, Douwe Dekker2, Jelle Zwaag1
1Department of Intensive Care Medicine, Radboudumc Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
Frontiers in immunology
|June 1, 2023
概括
由阿塔萨纳维尔诱导的高 bilirubin 水平,增强了抗氧化能力,并在实验性人类内毒素症期间预防了血管功能障碍,这表明 bilirubin 在急性炎症中起着保护作用.
科学领域:
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
- 心血管医学 心血管医学
背景情况:
- 炎症通过自由基的释放驱动疾病的发病.
- 血红素氧酶 (HO) 途径代谢血红素,产生比利鲁宾,一种强大的抗氧化剂.
- 胆红素在人类急性炎症中的作用及其血管效应仍然不清楚.
研究的目的:
- 调查阿塔扎纳维尔诱导的高 bilirubinemia对抗氧化能力,炎症和血管功能的影响在人类实验性内毒症.
- 评估在急性炎症反应期间,高高的非结合性胆红素水平的保护潜力.
主要方法:
- 20名健康的男性接受了阿塔扎纳维尔或安慰剂,随后是静脉注射脂多糖 (LPS) 来诱导实验性内毒性.
- 测量了胆红素水平,血抗氧化能力 (FRAP),细胞因子释放 (互白素-10),以及血管功能 (前臂囊膜).
- 进行了体外全血检测,以评估阿塔扎纳维尔对LPS诱导的细胞因子释放的直接作用.
主要成果:
- 阿扎纳维尔显著增加了总胆红素水平和血抗氧化能力 (FRAP) 的36% (p<0.0001).
- 超大胆血症减弱了介素-10的释放 (p=0.01),但没有改变促炎性细胞因子水平.
- 由LPS诱导的血管功能障碍在高 bilirubinemic受试者中被完全预防.
结论:
- 阿塔萨纳维尔诱导的高 bilirubinemia 增强抗氧化能力和减弱特定的炎症反应在实验内毒素.
- 升高的胆红素水平可以保护人体急性炎症的血管过敏反应.
- 研究结果表明,在炎症条件下调节胆红素水平具有潜在的治疗作用.
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