Nakazato Keiko, Yoshida Yuko, Takemori Ken, Kobayashi Katsuya, Sakamoto Atsuhiro
Department of Anesthesiology, Nippon Medical School, Tokyo, Japan.
Biomed Res. 2009 Feb;30(1):17-24. doi: 10.2220/biomedres.30.17.
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.
我们之前通过微阵列分析表明,七氟烷麻醉会影响大鼠多个器官中10000个基因中的177个基因的表达比率。在肝脏中检测到的基因改变数量最多,其中包括几个被表征为编码药物代谢酶(DME)的基因。在此,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存在差异,以及麻醉苏醒后这些改变会持续多长时间。从用七氟烷、异氟烷、丙泊酚或右美托咪定麻醉0或6小时的大鼠(每组n = 6)中获取肝脏,并在麻醉6小时后苏醒24小时的大鼠中获取肝脏。通过定量实时逆转录聚合酶链反应测量在先前研究中显示出最大改变的八个编码DME的基因,即Cyp7a1、Cyp2b15、Por、Nr1i2、Ces2、Ugt1a7、Abcb1a和Abcc2的mRNA表达比率。麻醉6小时后表达比率大多升高,并在麻醉苏醒后24小时恢复到对照水平。然而,一些基因的表达比率在麻醉苏醒后24小时仍保持升高。吸入麻醉和静脉麻醉之间存在差异,有趣的是,七氟烷和异氟烷之间以及丙泊酚和右美托咪定之间也存在差异。