所有血脑屏障细胞类型都表现出能够影响大脑中不同诺福维尔和埃姆特里西塔宾的新陈代谢和运输的能力
Hannah N Wilkins1, Stephen A Knerler2, Ahmed Warshanna1
1Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, United States.
血脑屏障 (BBB) 具有不同的细胞类型,可以代谢和运输药物,从而影响大脑的药物获取. 了解这些独特的BBB通路对于治疗神经系统疾病至关重要.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 细胞生物学 细胞生物学
背景情况:
- 血脑屏障 (BBB) 阻碍了药物输送到大脑,使神经系统疾病的治疗复杂化.
- 在药物处置中,BBB细胞类型 (内皮细胞,皮细胞,星细胞) 的特定作用尚未完全理解.
研究的目的:
- 在BBB研究药物运输和代谢机制,使用抗逆转录病毒药物特诺福维尔 (TFV) 和埃姆特里西塔宾 (FTC).
- 评估细胞类型对大脑药物处置的特定贡献.
主要方法:
- 在体内研究中使用 rhesus macaques,在体内实验中使用原始人体细胞.
- 评估了特定区域和细胞类型的药物代谢和TFV和FTC的传输.
主要成果:
- 观察到TFV,FTC及其代谢物的异质分布,不反映在脑脊液中.
- 所有BBB细胞类型都表现出功能性药物代谢酶和用于TFV/FTC吸收和激活的载体.
- 周细胞和星细胞表现出显著的药理活性,与肝细胞相比,对疾病和治疗敏感.
结论:
- BBB应该被视为一个独特的药理学实体,而不仅仅是肝脏的延伸.
- 每种BBB细胞类型的独特药物代谢和运输能力显著影响大脑的药物处置.
- 确定了BBB中的药理学活性通路,这些通路调节药物进入,并可能影响神经疾病治疗.
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