Effects of isoflurane on oxygen-glucose deprivation-induced changes of gene expression profiling in glial-neuronal cocultures.
Effects of isoflurane on oxygen-glucose deprivation-induced changes of gene expression profiling in glial-neuronal cocultures.
复制标题
异氟烷对神经胶质-神经元共培养物中氧-葡萄糖剥夺诱导的基因表达谱变化的影响。
DOI：
10.1111/j.1399-6576.2005.00760.x
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发表时间：
2005
影响因子：
2.1
通讯作者：
Zuo,Z
中科院分区：
文献类型：
--
作者：
Huang,Y;Zuo,Z
背景：异氟醚可减轻缺血所致的神经元损伤。这种效应的机制在很大程度上是未知的。我们假设异氟醚可以诱导保护性应激基因的表达，并降低细胞凋亡相关基因的表达。方法：采用基因芯片技术检测大鼠神经胶质细胞-神经元共培养中约1300个神经生物学相关基因的表达。结果：4种即刻早期基因/转录因子(早期生长反应1、c-fos、神经生长因子诱导因子A和Knox-24)在异氟醚、氧糖剥夺或异氟烷+氧糖剥夺条件下的表达水平均高于对照组的1.4倍。异氟醚可增加32 kDa热休克蛋白血红素加氧酶的mRNA表达，降低caspase-2、calain 1和Bcl2相关死亡激动剂的mRNA表达。在异氟醚+OGD条件下，这些效应仍然很明显。用逆转录-聚合酶链式反应检测基因芯片检测样本中Gβ1、早期生长反应1和死亡效应结构域蛋白DIFT的表达，结果与芯片技术揭示的实验条件下的变化规律一致。结论：异氟醚对神经胶质细胞-神经元共培养中多基因表达的影响与其抗缺血神经保护作用相一致。本研究揭示了异氟烷暴露后多种基因表达的协同变化(潜在保护性基因表达增加，潜在破坏性基因表达减少)。
Background:Isoflurane decreases ischemia‐induced neuronal injury. The mechanisms of this effect are largely unknown. We hypothesize that isoflurane induces expression of protective stress genes and decreases expression of apoptosis‐related genes.Methods:The mRNA expression of about 1300 genes related to neurobiology in rat glial‐neuronal cocultures was evaluated by microarray technology. Four experimental conditions were examined: control; 2% isoflurane; oxygen‐glucose deprivation (OGD, to simulate ischemiain vitro); or isoflurane (2%) plus OGD.Results:There were four immediate early genes/transcription factors (early growth response 1, c‐fos, nerve growth factor‐induced factor A and Knox‐24) whose mRNA expression was increased to more than 1.4‐fold of control levels under the conditions of isoflurane, OGD or isoflurane plus OGD. Isoflurane increased the mRNA expression of heme oxygenase, a 32‐kDa heat‐shock protein, and decreased the mRNA expression of caspase‐2, calpain 1 and the Bcl‐2‐associated death agonist. These isoflurane effects were still apparent under the condition of isoflurane plus OGD. The mRNA expression of Gβ1, early growth response 1 and the death effector domain‐containing protein DEFT in the samples used for microarray assay was determined by reverse transcriptase‐polymerase chain reaction, and the results were consistent with the patterns of changes across the experimental conditions as revealed by microarray technology.Conclusion:Our data suggest that the effects of isoflurane on the mRNA expression of multiple genes in glial‐neuronal cocultures are consistent with its neuroprotection against ischemia. A coordinated change in expression of many genes (increased expression of potentially protective gene and decreased expression of potentially damaging genes) after the exposure of isoflurane was revealed by this study.