在使用氨酸-血管酶系统调节剂和COVID相关的认知和脑血管功能障碍时,时间问题很重要
Mackenzi Meier1, Sara Becker1, Erica Levine1
1Department of Pharmacy Practice, School of Pharmacy, South University, Savannah, Georgia, United States of America.
PloS one
|July 29, 2024
概括
之前使用Renin-angiotensin系统 (RAS) 调节剂,如ACE抑制剂 (ACEI) 或 ангиотензин受体阻断剂 (ARB),可能会恶化COVID-19的认知问题. 然而,在感染后启动这些RAS调节器可能会提供保护性益处.
科学领域:
- 心血管研究研究心血管研究
- 神经科学是一个神经科学.
- 传染性疾病 传染性疾病
背景情况:
- 氨酸- ангиотензин系统 (RAS) 调节剂,包括氨酸受体阻断剂 (ARB) 和氨酸转化酶抑制剂 (ACEI),对于高血压管理至关重要.
- COVID-19感染与认知缺陷有关,包括记忆力丧失和混乱.
- RAS调节器影响血管素转化酶-2 (ACE-2) 表达,这是SARS-CoV-2入口的关键受体,与COVID-19严重程度形成复杂的关系.
研究的目的:
- 调查先前存在的RAS调节器治疗是否会加剧COVID-19引起的脑血管和认知功能障碍.
- 为了确定在COVID-19感染后启动RAS调节器治疗是否可以改善认知和脑血管功能.
- 测试假设,RAS调节器的预治疗会恶化COVID-19的影响,而后治疗提供保护.
主要方法:
- 一项临床研究确定了COVID-19患有高血压的患者,并根据入院前使用ACEI/ARBs将其分类为组.
- 对所有患者,在入院时评估了神经功能障碍.
- 一项临床前研究使用了人性化的ACE-2小鼠,给 SARS-CoV-2尖端蛋白,并评估洛萨坦 (ARB) 在尖端蛋白暴露前后对认知功能,大脑血流和脑血管完整性的影响.
主要成果:
- 在COVID-19之前服用ACEI/ARB的患者表现出较高的神经功能障碍率 (51%) 与未服用这些药物的患者相比 (27%).
- 在动物模型中,SARS-CoV-2尖端蛋白诱导了血管炎症,内皮细胞亡,并降低了脑血管密度,脑血流和认知功能.
- 洛萨坦前期治疗在小鼠中加剧了这些影响,而洛萨坦后期治疗显示出对尖端蛋白诱导的血管和神经损伤的保护作用.
结论:
- 临床研究结果表明,先前使用RAS调节剂可能会在COVID-19患者的血管和神经功能障碍中恶化.
- 在体内实验证实了这些发现,表明预治疗加剧了与SARS-CoV-2相关的功能障碍.
- 在暴露于SARS-CoV-2后启动RAS调制疗法在动物模型中显示了潜在的保护性益处,突出了关键的时间依赖效应.
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