Culley Deborah J, Yukhananov Rustam Y, Xie Zhongcong, Gali Reddy R, Tanzi Rudolph E, Crosby Gregory
Department of Anesthesia, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, 02115, USA.
Eur J Pharmacol. 2006 Nov 7;549(1-3):71-8. doi: 10.1016/j.ejphar.2006.08.028. Epub 2006 Aug 26.
We profiled changes in gene expression in the hippocampus 2 days after a 4 h general anesthetic with isoflurane and nitrous oxide. Eighteen month old Fisher 344 rats were anesthetized for 4 h with 1.2% isoflurane and 70% nitrous oxide (N=9) whereas control rats breathed 30% oxygen for 4 h (N=9). Rats were sacrificed 48 h later and RNA extracted from the hippocampus for gene expression profiling. Three gene arrays were used per group, with samples prepared by pooling RNA from three rats. Differentially expressed genes were analyzed based on a weighted error statistical model. Microarray results for 6 differentially expressed genes were verified with reverse transcriptase polymerase chain reaction. Compared to unanesthetized controls, 297 genes were differentially expressed 2 days following anesthesia (P<0.05). Of these, 113 are named genes; 64% were up-regulated and 36% were down-regulated. The majority of differentially expressed genes are implicated in cell stress and replication, signal transduction, transcription, protein biosynthesis, cell structure, and metabolism. The correlation between fold changes on array and reverse transcriptase polymerase chain reaction was good (R2=0.85) for the 6 genes examined with both methods. These results demonstrate that in rats general anesthesia is associated with persistent changes in hippocampal gene expression, suggesting that recovery of the brain from anesthesia is considerably slower than generally recognized.
我们研究了在使用异氟烷和氧化亚氮进行4小时全身麻醉后2天，海马体中基因表达的变化情况。18个月大的Fisher 344大鼠用1.2%异氟烷和70%氧化亚氮麻醉4小时（N = 9），而对照大鼠呼吸30%氧气4小时（N = 9）。48小时后处死大鼠，从海马体中提取RNA用于基因表达谱分析。每组使用三个基因芯片，样本通过合并三只大鼠的RNA制备。基于加权误差统计模型分析差异表达基因。用逆转录聚合酶链反应验证了6个差异表达基因的微阵列结果。与未麻醉的对照组相比，麻醉后2天有297个基因差异表达（P<0.05）。其中，113个是已知基因；64%上调，36%下调。大多数差异表达基因与细胞应激和复制、信号转导、转录、蛋白质生物合成、细胞结构和代谢有关。对于两种方法都检测的6个基因，芯片上的倍数变化与逆转录聚合酶链反应之间的相关性良好（R2 = 0.85）。这些结果表明，在大鼠中全身麻醉与海马体基因表达的持续变化有关，这表明大脑从麻醉中恢复的速度比普遍认为的要慢得多。
