Long noncoding NONRATT021972 siRNA normalized abnormal sympathetic activity mediated by the upregulation of P2X 7 recept
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ORIGINAL ARTICLE
Long noncoding NONRATT021972 siRNA normalized abnormal sympathetic activity mediated by the upregulation of P2X7 receptor in superior cervical ganglia after myocardial ischemia Guihua Tu 1 & Lifang Zou 1 & Shuangmei Liu 1 & Bing Wu 1 & Qiulan Lv 1 & Shouyu Wang 1 & Yun Xue 1 & Chunping Zhang 1 & Zhihua Yi 1 & Xi Zhang 1 & Guilin Li 1 & Shangdong Liang 1,2
Received: 1 February 2016 / Accepted: 11 May 2016 # Springer Science+Business Media Dordrecht 2016
Abstract 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 dec reased in th e MI rats that w ere treated with NONRATT021972 siRNA. Meanwhile, the increased P2X7 Guihua Tu, Lifang Zou, and Shuangmei Liu are Joint first authors. * Guilin Li [email protected] * Shangdong Liang [email protected] 1
Department of Physiology, Medical College of Nanchang University, Nanchang 330006, People’s Republic of China
2
Institute of Life Science of Nanchang University, Nanchang 330006, People’s Republic of China
mRNA and protein levels and the increased p-ERK1/2 expression in the SCG were also reduced. NONRATT021972 siRNA treatment inhibited the P2X 7 agonist BzATPactivated currents in HEK293 cells transfected with pEGFPP2X7. 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. Keywords P2X7 receptor . Long noncoding RNA . Superior cervical ganglia . Myocardial ischemia
Abbreviations ATP Adenosine triphosphate CK Creatine kinase CK-MB Creatine kinase isoform MB cTn-I Cardiac troponin I DBP Diastolic blood pressure ECG Electrocardiogram ELISA Enzyme-linked immunosorbent assay EPI Epinephrine HE staining Hematoxylin and eosin staining ERK1/2 Extracellular signal-regulated protein kinases HF High frequency HR Heart rate HRV Heart rate variability IOD Integrated optical density IL-6 Interleukin-6 ISH In situ hybr
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