Oei Gezina T M L, Heger Michal, van Golen Rowan F, Alles Lindy K, Flick Moritz, van der Wal Allard C, van Gulik Thomas M, Hollmann Markus W, Preckel Benedikt, Weber Nina C
Department of Anesthesiology, Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), University of Amsterdam, Amsterdam, The Netherlands.
Department of Experimental Surgery, University of Amsterdam, Amsterdam, The Netherlands.
Mol Med. 2015 Jan 20;20(1):516-26. doi: 10.2119/molmed.2014.00057.
Helium, a noble gas, has been used safely in humans. In animal models of regional myocardial ischemia/reperfusion (I/R) it was shown that helium conditioning reduces infarct size. Currently, it is not known how helium exerts its cytoprotective effects and which cell death/survival pathways are affected. The objective of this study, therefore, was to investigate the cell protective effects of helium postconditioning by PCR array analysis of genes involved in necrosis, apoptosis and autophagy. Male rats were subjected to 25 min of ischemia and 5, 15 or 30 min of reperfusion. Semiquantitative histological analysis revealed that 15 min of helium postconditioning reduced the extent of I/R-induced cell damage. This effect was not observed after 5 and 30 min of helium postconditioning. Analysis of the differential expression of genes showed that 15 min of helium postconditioning mainly caused upregulation of genes involved in autophagy and inhibition of apoptosis versus I/R alone. The results suggest that the cytoprotective effects of helium inhalation may be caused by a switch from pro-cell-death signaling to activation of cell survival mechanisms, which appears to affect a wide range of pathways.
氦气作为一种惰性气体,已在人体中安全使用。在局部心肌缺血/再灌注(I/R)动物模型中,研究表明氦预处理可减小梗死面积。目前,尚不清楚氦气如何发挥其细胞保护作用以及哪些细胞死亡/存活途径受到影响。因此,本研究的目的是通过对参与坏死、凋亡和自噬的基因进行PCR阵列分析,来研究氦后处理的细胞保护作用。雄性大鼠经历25分钟的缺血和5、15或30分钟的再灌注。半定量组织学分析显示,15分钟的氦后处理可减少I/R诱导的细胞损伤程度。在5分钟和30分钟的氦后处理后未观察到这种效果。基因差异表达分析表明,与单纯I/R相比,15分钟的氦后处理主要导致参与自噬的基因上调和凋亡受到抑制。结果表明,吸入氦气的细胞保护作用可能是由促细胞死亡信号向细胞存活机制激活的转变引起的,这似乎会影响广泛的途径。