Long noncoding NONRATT021972 siRNA normalized abnormal sympathetic activity mediated by the upregulation of P2X₇ receptor in superior cervical ganglia after myocardial ischemia

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• 作者：Guihua Tu ; Lifang Zou ; Shuangmei Liu ; Bing Wu ; Qiulan Lv…
• 关键词：P2X7 receptor ; Long noncoding RNA ; Superior cervical ganglia ; Myocardial ischemia
• 刊名：Purinergic Signalling
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：12
• 期：3
• 页码：521-535
• 全文大小：7,825 KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Biomedicine
  Pharmacology and Toxicology
  Human Physiology
  Neurosciences
  Cancer Research
  
• 出版者：Springer Netherlands
• ISSN：1573-9546
• 卷排序：12

文摘

Previous studies showed that the upregulation of the P2X₇ receptor in cervical sympathetic ganglia was involved in myocardial ischemic (MI) injury. The dysregulated expression of long noncoding RNAs (lncRNAs) participates in the onset and progression of many pathological conditions. The aim of this study was to investigate the effects of a small interfering RNA (siRNA) against the NONRATT021972 lncRNA on the abnormal changes of cardiac function mediated by the up-regulation of the P2X₇ receptor in the superior cervical ganglia (SCG) after myocardial ischemia. When the MI rats were treated with NONRATT021972 siRNA, their increased systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), low-frequency (LF) power, and LF/HF ratio were reduced to normal levels. However, the decreased high-frequency (HF) power was increased. GAP43 and tyrosine hydroxylase (TH) are markers of nerve sprouting and sympathetic nerve fibers, respectively. We found that the TH/GAP43 value was significantly increased in the MI group. However, it was reduced after the MI rats were treated with NONRATT021972 siRNA. The serum norepinephrine (NE) and epinephrine (EPI) concentrations were decreased in the MI rats that were treated with NONRATT021972 siRNA. Meanwhile, the increased P2X₇ mRNA and protein levels and the increased p-ERK1/2 expression in the SCG were also reduced. NONRATT021972 siRNA treatment inhibited the P2X₇ agonist BzATP-activated currents in HEK293 cells transfected with pEGFP-P2X₇. Our findings suggest that NONRATT021972 siRNA could decrease the upregulation of the P2X₇ receptor and improve the abnormal changes in cardiac function after myocardial ischemia.