使用新一代RNA测序法检测冷停跳液引起的左心室心肌转录谱的缺血性变化
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Using Next-generation RNA Sequencing to Examine Ischemic Changes Induced by Cold Blood Cardioplegia on the Human Left Ventricular Myocardium Transcriptome
背景与目的
目前关于人心肌缺血病理过程的确切机制尚不清楚。作者在基线时检测了体外循环患者左心室心肌的转录谱，之后暴露于冷停搏液诱导缺血作为人心肌缺血模型。
方 法
作者分别获取了45名行主动脉瓣置换术患者在基线时以及进行79分钟的心脏停搏后的活组织。样本是RNA序列，并分析了PartekR基因组(Partek公司，圣路易斯，MO)的差异表达。独创性途径分析(独创性系统、CA)和Biobase解释(Biobase GmbH是德国的)系统，它是用于功能和路径分析的。
结 果
在平均表达值大于5的4,098个基因中，90％被下调，9.1％上调。 其中1,241人差异显着。 基因本体分析揭示了免疫炎症反应和补体活化类别的显着下调，高度一致的是intelectin 1，蛋白多糖和分泌型白细胞肽酶抑制剂的下调。感兴趣的上调基因是FBJ小鼠骨肉瘤病毒基因同源物和血红蛋白基因血红蛋白α1（HBA1）和血红蛋白β。此外，转录因子结合位点的分析显示调节活性氧生成，凋亡，免疫，细胞因子产生和炎症反应的因素中的目标。
结 论
在行体外循环术的患者中，左心室表现出明显的基因表达变化，这为心室缺血的病理生理学提供了深入的了解，从而有助于在手术过程中减少对心肌的损伤。
原始文献摘要
Muehlschlegel J D, Christodoulou D C, Mckean D, et al. Using next-generation RNA sequencing to examine ischemic changes induced by cold blood cardioplegia on the human left ventricular myocardium transcriptome[J]. Anesthesiology, 2015, 122(3):537.
Background: The exact mechanisms that underlie the pathological processes of myocardial ischemia in humans are unclear. Cardiopulmonary bypass with cardioplegic arrest allows the authors to examine the whole transcriptional profile of human left ventricular myocardium at baseline and after exposure to cold cardioplegia-induced ischemia as a human ischemia model.
Methods: The authors obtained biopsies from 45 patients undergoing aortic valve replacement surgery at baseline and after an average of 79 min of cold cardioplegic arrest. Samples were RNA sequenced and analyzed with the PartekR Genomics Suite (Partek Inc., St. Louis, MO) for differential expression. Ingenuity Pathway Analysis (Ingenuity Systems, Redwood City, CA) and Biobase ExPlain (Biobase GmbH, Wolfenbuettel, Germany) systems were used for functional and pathway analyses.
Results: Of the 4,098 genes with a mean expression value greater than 5, 90% were down-regulated and 9.1% were up-regulated. Of those, 1,241 were significantly differentially expressed. Gene ontology analysis revealed significant down-regulation in immune inflammatory response and complement activation categories and highly consistent was the down-regulation of intelectin 1, proteoglycan, and secretory leukocyte peptidase inhibitor. Up-regulated genes of interest were FBJ murine osteosarcoma viral oncogene homolog and the hemoglobin genes hemoglobin α1 (HBA1) and hemoglobin β. In addition, analysis of transcription factor–binding sites revealed interesting targets in factors regulating reactive oxygen species production, apoptosis, immunity, cytokine production, and inflammatory response.
Conclusions: The authors have shown that the human left ventricle exhibits significant changes in gene expression in response to cold cardioplegia-induced ischemia during cardiopulmonary bypass, which provides great insight into the pathophysiology of ventricular ischemia, and thus, may help guide efforts to reduce myocardial damage during surgery.
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