慢性阿里皮普拉和特拉佐多药房对系统和大脑胆固醇生物合成的影响
Zeljka Korade1,2, Allison Anderson3, Marta Balog4
1Department of Pediatrics, College of Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Biomolecules
|September 28, 2023
概括
同时使用阿里皮普拉 (ARI) 和特拉佐 (TRZ) 会影响小鼠的胆固醇生物合成. 这两种药物分发到大脑和器官,改变了固醇配置和蛋白质表达,观察到明显的性别差异.
科学领域:
- 神经药理学神经药理学
- 生物化学 生物化学
- 代谢过程中的代谢.
背景情况:
- 同时使用药物在复杂的精神疾病中很常见.
- 阿里皮普拉 (ARI) 和特拉佐 (TRZ) 经常同时被处方.
- 无论是ARI还是TRZ都抑制了7-脱胆固醇减少酶 (DHCR7) 酶,影响胆固醇合成.
研究的目的:
- 评估ARI和TRZ在大脑和系统器官中的分布.
- 评估同步ARI和TRZ治疗对胆固醇生物合成的影响.
- 调查药物分发和代谢效应的潜在基于性别的差异.
主要方法:
- 成年小鼠在21天内同时服用ARI和TRZ.
- 液体染色学-并联质谱学 (LC-MS/MS) 用于分析大脑和各种器官中的药物水平,代谢物和类固醇.
- 在皮质中测量了DHCR7和IBA1的蛋白质表达.
主要成果:
- 在大脑和器官中检测到ARI,TRZ及其代谢物,从而改变了类固醇的概况.
- 观察到显著的性别差异,雌性小鼠表现出更高的ARI周转率和改变的大脑胆固醇清除.
- ARI和TRZ暴露降低了IBA1并在皮质中增加了DHCR7蛋白表达,对脏,肝脏和血清中的类固醇概况有系统性影响.
结论:
- 同时服用ARI和TRZ会影响中枢神经系统和全身醇生物合成.
- 观察到的固醇概况和蛋白质表达的改变凸显了联合药物使用的潜在后果.
- 需要进一步的研究,以了解由于ARI和TRZ联合治疗而改变的固醇生物合成的长期影响.
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