LncRNA NONRATT021972 siRNA regulates neuropathic pain behaviors in type 2 diabetic rats through the P2X7 receptor in dorsal root ganglia.

LncRNA NONRATT021972 siRNA regulates neuropathic pain behaviors in type 2 diabetic rats through the P2X7 receptor in dorsal root ganglia.
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LncRNA NONRATT021972 siRNA 通过背根神经节中的 P2X(7) 受体调节 2 型糖尿病大鼠的神经病理性疼痛行为

DOI:
10.1186/s13041-016-0226-2
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发表时间:
2016-04-23
期刊:
影响因子:
3.6
通讯作者:
Liang S
Liang S
中科院分区:
医学3区
文献类型:
--
作者:
Liu S;Zou L;Xie J;Xie W;Wen S;Xie Q;Gao Y;Li G;Zhang C;Xu C;Xu H;Wu B;Lv Q;Zhang X;Wang S;Xue Y;Liang S

文献摘要

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长非蛋白质编码RNA(LncRNAs)参与神经系统疾病的病理过程。NONRATT021972是一个IncRNA。本研究探讨了小干扰RNA(SiRNA)对大鼠背根神经节(DRG)中P2X7受体介导的糖尿病神经病理性疼痛(DNP)的影响。结果显示,糖尿病组背根神经节中NONRATT021972的表达明显高于对照组。经NONRATT021972 siRNA处理后,糖尿病大鼠背根神经节中NONRATT021972的表达减少。NONRATT021972 siRNA治疗可提高大鼠尾神经的机械戒断阈值(MWT)、热戒断潜伏期(TWL)和感觉神经传导速度(SNCV)。静脉注射NONRATT021972 siRNA后,大鼠背根神经节中P2X7、胶质纤维酸性蛋白和肿瘤坏死因子-ɑ的表达水平降低。应用生物信息学技术预测了RNA(NONRATT021972)和蛋白质(P2X7)之间的相互作用。DM大鼠背根神经节非神经元(卫星胶质细胞)的BzATP激活电流较对照组显著增加。NONRATT021972 siRNA处理可抑制转染pEGFP-P2X7的HEK293细胞的ATP激活电流。NONRATT021972 siRNA治疗可降低2型DM大鼠背根神经节中P2X7基因和蛋白的表达水平,抑制卫星胶质细胞(SGCs)的激活。此外,NONRATT021972 siRNA治疗减少了炎症因子(肿瘤坏死因子-α)的释放,从而抑制了背根节神经元的兴奋性,并减轻了2型DM大鼠的机械和热痛觉过敏。
Long non-protein-coding RNAs (lncRNAs) are involved in the pathological processes of nervous system diseases. NONRATT021972 is an lncRNA. This study explores the effects of lncRNA NONRATT021972 small interference RNA (siRNA) on diabetic neuropathic pain (DNP) mediated by the P2X7 receptor in the rat dorsal root ganglia (DRG). Our results show that NONRATT021972 expression was significantly higher in the DRG of diabetes mellitus (DM) group compared with control group. NONRATT021972 expression in the DRG was reduced when DM rats were treated with NONRATT021972 siRNA. NONRATT021972 siRNA treatment in type 2 DM rats increased the mechanical withdrawal threshold (MWT), the thermal withdrawal latency (TWL) and the sensory nerve conduction velocity (SNCV) of rat tail nerves. After intravenous injection with NONRATT021972 siRNA in DM rats, the P2X7, GFAP and TNF-ɑ expression levels in DRG were decreased. An interaction between the RNA (NONRATT021972) and protein (P2X7) was predicted by the application of bioinformatics technology. The BzATP-activated currents in DRG non-neurons (satellite glial cells) of DM rats were significantly increased compared to control rats. NONRATT021972 siRNA treatment inhibited the ATP-activated currents in HEK293 cells transfected with pEGFP-P2X7. NONRATT021972 siRNA treatment can decrease the expression levels of P2X7 mRNA and protein and inhibit the activation of satellite glial cells (SGCs) in the DRG of type 2 DM rats. Moreover, NONRATT021972 siRNA treatment reduced the release of inflammatory factors (TNF-α), thereby inhibiting the excitability of DRG neurons and reducing mechanical and thermal hyperalgesia in type 2 DM rats.