Expressions of genes encoding drug-metabolizing enzymes are altered after sevoflurane, isoflurane, propofol or dexmedetomidine anesthesia

Expressions of genes encoding drug-metabolizing enzymes are altered after sevoflurane, isoflurane, propofol or dexmedetomidine anesthesia
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DOI:
10.2220/biomedres.30.17
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发表时间:
2009-02-01
影响因子:
1.2
通讯作者:
Sakamoto, Atsuhiro
Sakamoto, Atsuhiro
中科院分区:
医学4区
文献类型:
--
作者:
Nakazato, Keiko;Yoshida, Yuko;Sakamoto, Atsuhiro

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我们之前通过微阵列分析表明,七氟醚麻醉影响了大鼠多个器官中10000个基因中177个的表达率。肝脏中检测到的变异基因数量最多。包括几个编码药物代谢酶(DMEs)的基因。在这里,我们研究了吸入麻醉和静脉麻醉后药代动力学基因表达的改变是否不同,以及麻醉苏醒后这种改变持续多久。取七氟醚、异氟醚、异丙酚或右美托咪定麻醉0或6 h的大鼠肝脏(每组n = 6只),麻醉6 h后唤醒24 h。采用实时定量逆转录-聚合酶链反应法测定8个编码DMEs的基因Cyp7a1、Cyp2b15、Por、Nr1i2、Ces2、Ugt1a7、-Abcb1a和Abcc2的mRNA表达比,这些基因在既往研究中变化最大。在麻醉6 h后表达率增加,苏醒24 h后恢复到对照水平。然而,一些基因的表达率在麻醉苏醒后24小时内仍然升高。吸入麻醉和静脉麻醉之间存在差异,有趣的是,七氟醚和异氟醚以及异丙酚和右美托咪定之间也存在差异。
We previously showed that sevoflurane anesthesia affected the expression ratios of 177 of 10,000 genes in multiple organs of rats by microarray analyses. The maximum number of altered genes was detected in the liver. and included several genes characterized as encoding drug-metabolizing enzymes (DMEs). Here, we investigated whether alterations of pharmacokinetic gene expressions after anesthesia differed between inhalation and intravenous anesthesia, and how long the alterations persisted after awakening from anesthesia. Livers were obtained from rats (n = 6 per group) anesthetized with sevoflurane, isoflurane, propofol or dexmedetomidine for 0 or 6 h, and rats awakened for 24 h after anesthesia for 6 h. The mRNA expression ratios of eight genes encoding DMEs that showed the greatest alterations in the previous study, namely Cyp7a1, Cyp2b15, Por, Nr1i2, Ces2, Ugt1a7,-Abcb1a and Abcc2, were measured by quantitative real-time reverse transcriptase-polymerase chain reaction. The expression ratios were mostly increased after 6 h of anesthesia and returned to their control levels at 24 h after awakening from anesthesia. However, the expression ratios of some genes remained elevated for 24 h after awakening from anesthesia. There were differences between inhalation and intravenous anesthesia, and interestingly, between sevoflurane and isoflurane and between propofol and dexmedetomidine.