低压缺氧对大鼠脑皮质基因表达谱及其TAC1和MT1A变化的影响

关键词：低压缺氧  脑皮质  基因表达谱

Keywords:hypobaric hypoxia  cerebral cortex  gene expression profile

摘要：

      摘要 目的：研究低压缺氧对大鼠脑皮质基因表达谱及其TAC1和MT1A变化的影响。 方法：将24只Wistar大鼠随机分为对照组、3000m缺氧组和7000m缺氧组，每组8只。采用低压缺氧舱建立急性高原缺氧模型，应用基因芯片检测缺氧24h大鼠脑皮质差异表达基因，应用qRT-PCR定量检测TAC1和MT1A基因表达水平。 结果：3000m缺氧组共有已知差异表达基因215个，其中29个上调，186个下调。上调基因主要有TAC1、Rgs9、Serpinb6a、Adora2a、Penk1，下调基因主要有Siah1a、Acvr1、Btbd1、Cir、Abi1，差异表达最明显的基因是TAC1。7000m缺氧组共有已知差异表达基因205个，其中21个上调，184个下调。上调基因主要有MT1A、Cml3、Wfdc1、Tfpi、Vwf，下调基因主要有Zfp238、Atad1、Leprotl1、Tpm4、Fxr1，差异表达最明显的基因是MT1A。两组差异表达基因中共表达基因有120个，其中7个上调，113个下调。上调基因主要有TAC1、Serpinb6a、Ephx1、Cml3、Olr606，下调基因主要有Acvr1、Btbd1、Leprotl1、Unc119、Canx。qRT-PCR实验证实低压缺氧脑皮质TAC1和MT1A上调。 结论：低压缺氧程度不同，脑皮质基因表达谱亦不同。TAC1对缺氧较为敏感，轻、重度高原缺氧表达均上调；MT1A对缺氧反应较为迟钝，轻度缺氧下MT1A基因表达水平不变甚至下降，而重度缺氧时MT1A基因显著上调。

Abstract:

      Abstract Objective：To study the effects of hypobaric hypoxia on the changes of gene expression profile and TAC1 and MT1A in rats' cerebral cortex. Method：Twenty-four rats were randomly divided into control group, 3000m hypoxia group and 7000m hypoxia group(8 rats in each group). The acute plateau hypoxia model was established in hypobaric hypoxia cabin, the differential expression genes were detected by chip technology in cerebral cortex of rats with 24h hypoxia, and the expression levels of TAC1 and MT1A were measured quantitatively by qRT-PCR. Result：In the 3000m hypoxia group,215 differential expression genes were found, 29 of which were up-regulated and 186 down-regulated. The up-regulated genes were mainly TAC1,Rgs9,Serpinb6a, Adora2a and Penk1. The down-regulated genes were mainly Siah1a,Acvr1,Btbd1,Cir and Abi1,and the most obvious expression gene was TAC1. In the 7000m hypoxia group, 205 differentially expression genes were found, 21 of which were expressed and 184 down-regulated. Up-regulated genes were mainly MT1A,Cml3,Wfdc1,Tfpi and Vwf. Down-reg ulated genes were mainly Zfp238, Atad1, Leprotl1, Tpm4 and Fxr1, and the most obvious expressed gene was MT1A. In the two sets of differential expression genes, 119 genes were co-expressed, 6 genes were up-regulated and 113 were down-regulated. The up-regulated genes were mainly TAC1, Ephx1, Cml3, Olr606 and Dusp7. The down-regulated genes were mainly Acvr1, Btbd1, Leprotl1, Unc119 and Canx. TAC1 and MT1A in hypobaric hypoxia cerebral cortex were up-regulated, which were confirmed by qRT-PCR experiments. Conclusion：The difference of cerebral cortical gene expression profiling were according to the changes of hypobaric hypoxia, meanwhile. TAC1 seemed to be more sensitive to hypoxia, of which the expression were up-regulated in either the mild plateau hypoxia model or the severe one. The responses of MT1A to hypoxia were relatively blunted, and in the mild hypoxia model, the expression levels of gene MT1A were stable or even reduced, but in the severe hypoxia model, it were significantly up-regulated.