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

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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长非编码 NONRATT021972 siRNA 使心肌缺血后颈上神经节 P2X7 受体上调介导的异常交感神经活动正常化。

DOI:
10.1007/s11302-016-9518-3
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发表时间:
2016-09-01
影响因子:
3.5
通讯作者:
Liang, Shangdong
Liang, Shangdong
中科院分区:
医学3区
文献类型:
--
作者:
Tu, Guihua;Zou, Lifang;Liang, Shangdong

文献摘要

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既往研究表明颈交感神经节P2X(7)受体的上调与心肌缺血(MI)损伤有关。长链非编码 RNA (lncRNA) 的表达失调参与了许多病理状况的发生和进展。本研究的目的是探讨针对NONRATT021972 lncRNA的小干扰RNA(siRNA)对心肌缺血后颈上神经节(SCG)P2X(7)受体上调介导的心功能异常变化的影响。当MI大鼠接受NONRATT021972 siRNA治疗时,其升高的收缩压(SBP)、舒张压(DBP)、心率(HR)、低频(LF)功率和LF/HF比值均降至正常水平。然而,减少的高频(HF)功率却增加了。 GAP43 和酪氨酸羟化酶 (TH) 分别是神经萌芽和交感神经纤维的标记。我们发现 MI 组的 TH/GAP43 值显着升高。然而,用 NONRATT021972 siRNA 治疗 MI 大鼠后,该值有所减少。用 NONRATT021972 siRNA 治疗的 MI 大鼠的血清去甲肾上腺素 (NE) 和肾上腺素 (EPI) 浓度降低。同时,SCG中增加的P2X(7) mRNA和蛋白水平以及增加的p-ERK1/2表达也减少。 NONRATT021972 siRNA 处理抑制 pEGFP-P2X(7) 转染的 HEK293 细胞中 P2X(7) 激动剂 BzATP 激活的电流。我们的研究结果表明,NONRATT021972 siRNA 可以减少 P2X(7) 受体的上调,改善心肌缺血后心功能的异常变化。
Previous studies showed that the upregulation of the P2X(7) 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 P2X(7) 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 P2X(7) 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 BzATP-activated currents in HEK293 cells transfected with pEGFP-P2X(7). Our findings suggest that NONRATT021972 siRNA could decrease the upregulation of the P2X(7) receptor and improve the abnormal changes in cardiac function after myocardial ischemia.