Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri, USA.
J Surg Res. 2013 May;181(2):272-8. doi: 10.1016/j.jss.2012.06.053. Epub 2012 Jul 16.
This study was undertaken to investigate alterations of group II phospholipase A2 (PLA2) gene expression and its underlying mechanism in rat heart during different phases of sepsis.
Sepsis was induced by cecal ligation and puncture (CLP). Experiments were divided into three groups, control, early sepsis, and late sepsis. Early and late sepsis refers to those animals sacrificed at 9 and 18 h, respectively, after CLP. PLA2 enzyme activity, group II PLA2 protein level, messenger RNA (mRNA) abundance, transcription rate, and half-life were measured.
PLA2 activity was decreased by 29% during early sepsis but it was increased by 49% during late sepsis. Group II PLA2 protein level was decreased by 27% during early sepsis but it was increased by 35.3% during late sepsis. Group II PLA2 mRNA was decreased by 21% during early sepsis but it was increased by 141% during late sepsis. The transcription rate of group II PLA2 mRNA was reduced by 25% during early sepsis but it was elevated by 67% during late sepsis. The half-life of group II PLA2 mRNA remained unaltered during early and late phases of sepsis.
These results demonstrate that PLA2 activity, group II PLA2 protein level, the mRNA abundance, and transcription rate were concurrently underexpressed during early sepsis, while they were overexpressed during late sepsis, with no change in the degradation of gene transcript. These data indicate that the biphasic changes in group II PLA2 gene expression are regulated transcriptionally during sepsis.
本研究旨在探讨在脓毒症不同阶段大鼠心脏中 II 组磷脂酶 A2(PLA2)基因表达的变化及其潜在机制。
采用盲肠结扎穿孔(CLP)法诱导脓毒症。实验分为三组:对照组、早期脓毒症组和晚期脓毒症组。早期和晚期脓毒症分别指 CLP 后 9 和 18 小时处死的动物。测量 PLA2 酶活性、II 组 PLA2 蛋白水平、信使 RNA(mRNA)丰度、转录率和半衰期。
早期脓毒症时 PLA2 活性降低 29%,晚期脓毒症时增加 49%。早期脓毒症时 II 组 PLA2 蛋白水平降低 27%,晚期脓毒症时增加 35.3%。早期脓毒症时 II 组 PLA2 mRNA 减少 21%,晚期脓毒症时增加 141%。早期脓毒症时 II 组 PLA2 mRNA 的转录率降低 25%,晚期脓毒症时升高 67%。早期和晚期脓毒症时 II 组 PLA2 mRNA 的半衰期保持不变。
这些结果表明,在早期脓毒症时 PLA2 活性、II 组 PLA2 蛋白水平、mRNA 丰度和转录率均表达下调,而在晚期脓毒症时则表达上调,基因转录物的降解无变化。这些数据表明,II 组 PLA2 基因表达的双相变化在脓毒症期间受转录调控。