lncRNA NONRATT021972 siRNA Decreases Diabetic Neuropathic Pain Mediated by the P2X3 Receptor in Dorsal Root Ganglia
lncRNA NONRATT021972 siRNA Decreases Diabetic Neuropathic Pain Mediated by the P2X3 Receptor in Dorsal Root Ganglia
复制标题
lncRNA NONRATT021972 siRNA 减少背根神经节 P2X(3) 受体介导的糖尿病神经病理性疼痛
DOI：
10.1007/s12035-015-9632-1
复制
发表时间：
2017-01-01
影响因子：
5.1
通讯作者：
Liang, Shangdong
中科院分区：
文献类型：
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作者：
Peng, Haiying;Zou, Lifang;Liang, Shangdong
长链非编码RNA（lncRNA）参与生理和病理生理过程。2型糖尿病（T2 DM）占所有糖尿病（DM）病例的90%以上。糖尿病神经病理性疼痛（DNP）是T2 DM的常见并发症。本研究旨在探讨lncRNANONRATT 021972小干扰RNA（siRNA）对背根神经节（DRG）P2 X（3）受体介导的DNP的影响。这些实验表明，在T2 DM大鼠模型（腹腔注射30 mg/kg STZ）中，DRG中NONRATT 021972的表达水平增加。T2 DM患者血清中NONRATT 021972的浓度高于对照健康受试者。与对照组相比，T2 DM组大鼠的机械缩足阈（MWT）和热缩足潜伏期（TWL）降低。NONRATT 021972 siRNA治疗组的MWT和TWL均高于T2 DM组。T2 DM大鼠DRG中P2 X（3）蛋白和信使RNA（mRNA）的表达水平高于对照组，而NONRATT 021972 siRNA治疗组的P2 X（3）蛋白和mRNA的表达水平显著低于T2 DM大鼠。与T2 DM大鼠相比，用NONRATT 021972 siRNA处理的T2 DM大鼠血清中肿瘤坏死因子-α（TNF-α）水平显著降低。NONRATT 021972 siRNA抑制T2 DM DRG中ERK 1/2的磷酸化和激活。因此，NONRATT 021972 siRNA治疗可抑制P2 X（3）受体的上调表达和活化，并减少T2 DM大鼠中由促炎细胞因子TNF-α增强的痛觉过敏。
Long noncoding RNAs (lncRNAs) participate in physiological and pathophysiological processes. Type 2 diabetes mellitus (T2DM) accounts for more than 90 % of all cases of diabetes mellitus (DM). Diabetic neuropathic pain (DNP) is a common complication of T2DM. The aim of this study was to investigate the effects of lncRNA NONRATT021972 small interference RNA (siRNA) on DNP mediated by the P2X(3) receptor in dorsal root ganglia (DRG). These experiments showed that the expression levels of NONRATT021972 in DRG were increased in the T2DM rat model (intraperitoneal injection of STZ with 30 mg/kg). The concentration of NONRATT021972 in T2DM patient serum was higher compared to control healthy subjects. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in T2DM rats were lower compared to control rats. MWT and TWL in T2DM rats treated with NONRATT021972 siRNA were higher compared with those in T2DM rats. The expression levels of the P2X(3) protein and messenger RNA (mRNA) of T2DM rat DRG were higher compared to the control, while those in T2DM rats treated with NONRATT021972 siRNA were significantly lower compared to T2DM rats. The level of tumor necrosis factor-alpha (TNF-alpha) in the serum of T2DM rats treated with NONRATT021972 siRNA was significantly decreased compared with T2DM rats. NONRATT021972 siRNA inhibited the phosphorylation and activation of ERK1/2 in T2DM DRG. Thus, NONRATT021972 siRNA treatment may suppress the upregulated expression and activation of the P2X(3) receptor and reduce the hyperalgesia potentiated by the pro-inflammatory cytokine TNF-alpha in T2DM rats.