Department of Pediatrics, PICU, Shengjing Hospital of China Medical University, No.36, SanHao Street, Shenyang City, Liaoning Province, 110004, People's Republic of China.
Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA.
Inflammation. 2019 Dec;42(6):1990-2002. doi: 10.1007/s10753-019-01060-8.
Septic shock with heart dysfunction is common in intensive care units. However, the mechanism underlying myocardial depression is still unclear. Whether circular RNA (circRNA) or microRNA (miRNA) profiles differ between patients with and without myocardial depression is unknown. We generated a hypodynamic septic shock model induced by lipopolysaccharide (LPS) in adolescent rats. A total of 12 rats were utilized and heart tissue from each was collected. RNA sequencing was performed on left ventricular tissue. We focused on features of circRNAs and miRNAs, predicting their function by bioinformatic analysis and constructing circRNA-associated and miRNA-associated regulatory networks in heart tissue. We detected 851 circRNAs in heart samples, and 11 showed differential expression. A total of 639 annotated miRNAs and 91 novel miRNAs were explored including 78 showing differential expression between the two groups. We then constructed the most comprehensive circRNA-associated and miRNA-associated networks to explore their regulatory relationship in septic heart tissue, and demonstrated that different networks could potentially participate in and regulate the pathological process of sepsis. Furthermore, gene ontology term enrichment indicated miRNAs, and miRNA-mRNA networks could be associated with regulation and metabolic process, or influence cellular functions. The construction of regulator networks could improve the understanding of the basic molecular mechanisms underlying myocardial depression. It will be important for future investigations to ascertain the biological mechanisms present during the development of sepsis-induced myocardial depression to influence approaches to treatment.
脓毒性休克伴心功能障碍在重症监护病房很常见。然而,心肌抑制的机制尚不清楚。是否存在circRNA(环状 RNA)或 miRNA(微小 RNA)谱在有或没有心肌抑制的患者之间存在差异尚不清楚。我们在青少年大鼠中生成了由脂多糖(LPS)诱导的低动力脓毒性休克模型。共使用了 12 只大鼠,收集了每只大鼠的心脏组织。对左心室组织进行了 RNA 测序。我们专注于 circRNA 和 miRNA 的特征,通过生物信息学分析预测它们的功能,并构建心脏组织中的 circRNA 相关和 miRNA 相关调控网络。我们在心脏样本中检测到 851 个 circRNAs,其中 11 个显示出差异表达。共探索了 639 个注释 miRNA 和 91 个新 miRNA,其中 78 个在两组之间显示出差异表达。然后,我们构建了最全面的 circRNA 相关和 miRNA 相关网络,以探索它们在脓毒症心脏组织中的调控关系,并表明不同的网络可能参与并调节脓毒症的病理过程。此外,基因本体论术语富集表明,miRNA 和 miRNA-mRNA 网络可能与调节和代谢过程相关,或影响细胞功能。调控网络的构建可以提高对心肌抑制基本分子机制的理解。未来的研究确定脓毒症诱导的心肌抑制发展过程中的生物学机制将对治疗方法产生重要影响。