Effect of Therapeutic Mild Hypothermia on the Genomics of the Hippocampus After Moderate Traumatic Brain Injury in Rats
Effect of Therapeutic Mild Hypothermia on the Genomics of the Hippocampus After Moderate Traumatic Brain Injury in Rats
复制标题
亚低温治疗对中度脑外伤大鼠海马基因组的影响
DOI：
10.1227/01.neu.0000378023.81727.6e
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发表时间：
2010-09-01
期刊：
影响因子：
4.8
通讯作者：
Liang, Yu-min
中科院分区：
文献类型：
--
作者：
Feng, Jun-feng;Zhang, Kui-ming;Liang, Yu-min
背景：外伤性脑损伤（TBI）是引起发病率和死亡率的主要原因，是一个严重的公共卫生问题。目的探讨亚低温对脑外伤后海马基因表达的影响，探讨亚低温对脑外伤后神经保护的分子机制。方法大鼠外伤后进行亚低温（1组：n = 3, 33°C, 3H）或常温（2组：n = 3, 37°C, 3H）治疗。采用6个基因组阵列检测同侧海马基因表达谱。然后进行功能聚类和基因本体分析。另取20只大鼠随机分为4组（每组5只）：第3组，假正常；第4组，假低温；第5组为tbi - normalmia；第6组tbi低温治疗。采用实时荧光定量反转录聚合酶链反应检测特异性选择基因。结果低温组133个转录本与常温组差异有统计学意义，其中57个转录本上调，76个转录本下调（P < 0.01）。这些基因大多参与各种病理生理过程，有些对细胞存活至关重要。分析显示，9个基因本体类别受到低温的显著影响，其中受影响最大的类别是突触组织和生物发生（上调）和炎症反应调节（下调）。与假常温组比较，低体温组、TBI组或TBI +低温组均可调节Ank3、Cmbp、Nrxn3、Tgm2和Fcgr3 mRNA的表达。TBI组低温显著调节其mRNA表达。结论创伤后亚低温对海马基因表达谱有显著影响，尤其是9个基因本体类别的基因表达谱。这些基因的差异表达可能与脑外伤后亚低温脑保护的最基本分子机制有关。
BACKGROUNDTraumatic brain injury (TBI), a major cause of morbidity and mortality, is a serious public health concern. OBJECTIVETo evaluate the effect of mild hypothermia on gene expression in the hippocampus and to try to elucidate molecular mechanisms of hypothermic neuroprotection after TBI. METHODSRats were subjected to mild hypothermia (group 1: n = 3, 33°C, 3H) or normothermia (group 2: n = 3; 37°C, 3H) after TBI. Six genome arrays were applied to detect the gene expression profiles of ipsilateral hippocampus. Functional clustering and gene ontology analysis were then carried out. Another 20 rats were randomly assigned to 4 groups (n = 5 per group): group 3, sham-normothermia; group 4, sham-hypothermia; group 5, TBI-normothermia; and group 6, TBI-hypothermia. Real-time fluorescent quantitative reverse-transcription polymerase chain reaction was used to detect specific selected genes. RESULTSWe found that 133 transcripts in the hypothermia group were statistically different from those in the normothermia group, including 57 transcripts that were upregulated and 76 that were downregulated after TBI (P < .01). Most of these genes were involved in various pathophysiological processes, and some were critical to cell survival. Analysis showed that 9 gene ontology categories were significantly affected by hypothermia, including the most affected categories: synapse organization and biogenesis (upregulated) and regulation of inflammatory response (downregulated). The mRNA expression of Ank3, Cmbp, Nrxn3, Tgm2, and Fcgr3 was regulated by hypothermia, TBI, or a combination of TBI and hypothermia compared with the sham-normothermia group. Their mRNA expression was significantly regulated by hypothermia in TBI groups. CONCLUSIONPosttraumatic mild hypothermia has a significant effect on the gene expression profiles of the hippocampus, especially those genes belonging to the 9 gene ontology categories. Differential expression of those genes may be involved in the most fundamental molecular mechanisms of cerebral protection by mild hypothermia after TBI.