在心脏的不同区域的基因表达
1Fraunhofer Institute of Toxicology and Aerosol Research, Department of Molecular Toxicology and Pharmacokinetics, Hannover, Germany.
Lancet (London, England)
|April 18, 2000
概括
人心中的药物代谢主要位于右心室,特别是维拉帕米尔. 这种局部化的P450单氧化酶活性可能解释了为什么一些心脏药物不有效.
科学领域:
- 心脏病学 心脏病学
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
背景情况:
- 细胞染色体P450单氧酶 (CYP450) 对于药物代谢至关重要,但它们在人类心脏中的作用在很大程度上仍未被描述.
- 之前没有研究过心脏CYP450酶对维拉帕米尔的代谢.
研究的目的:
- 在人类心脏的不同区域研究主要的人类CYP450酶的基因表达.
- 通过检查心脏组织中的维拉帕米尔代谢来确定组织特异性CYP450表达的功能意义.
主要方法:
- 对人工心脏 (扩张性心肌病,动脉干转移),肝脏,肺部和正常心脏组织中CYP450酶的基因表达分析.
- 使用心室组织对维拉帕米尔进行微体代谢分析.
主要成果:
- 在右心室中观察到CYP450 1A1,2B6/7,2C8-19,2D6和4B1mRNA的主要表达.
- 由于CYP2D6在右心室的单边表达在β-阻断剂代谢中的作用,因此具有重要意义.
- 维拉帕米尔的新陈代谢局限于右心室,与基因表达相关.
- 肝脏和肺部普遍存在的CYP3A基因在人类心脏组织中不存在.
- 在整个心脏和大血管中检测到了环氧化酶,CYP2E1和含有黄素的单氧基酶2和5的mRNA.
结论:
- 细胞染色体P450单氧酶基因表达和维拉帕米尔代谢主要局限于人心的右侧.
- 这种右侧心脏代谢可能解释了某些心脏选择性药物的有效性降低.
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