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Id2基因沉默可减轻慢性压迫性损伤后的慢性神经性疼痛。

Silencing of Id2 Alleviates Chronic Neuropathic Pain Following Chronic Constriction Injury.

作者信息

Jiang Liuming, Wu Qun, Yang Tao

机构信息

Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, 2 Fuxue Road, Wenzhou, Zhejiang, 325000, China.

出版信息

J Mol Neurosci. 2016 May;59(1):99-105. doi: 10.1007/s12031-016-0713-z. Epub 2016 Jan 15.

DOI:10.1007/s12031-016-0713-z
PMID:26768262
Abstract

Inhibitor of DNA binding/differentiation 2 (Id2) belongs to a helix-loop-helix family of proteins. Recent studies have showed that Id2 plays a pivotal role in neuronal survival and neuroprotection. However, under neuropathic pain conditions, the role of Id2 is still unclear. In this study, we investigated the effect of Id2 on neuropathic pain in a rat chronic constriction injury (CCI) model. Our results demonstrated that Id2 was upregulated in the dorsal root ganglion (DRG) in a CCI rat in a time-dependent manner. Intrathecal short-hairpin RNA (shRNA)-Id2 attenuates mechanical allodynia and thermal hyperalgesia in CCI rats, and inhibits the expression of TNF-α and IL-1β in the DRG in CCI rats. Furthermore, knockdown of Id2 reduces the expression of NF-κB p65 in the DRG of CCI rats. Taken together, our findings suggest that knockdown of Id2 may alleviate neuropathic pain by inhibiting the NF-κB activation to inhibit the production of pro-inflammatory mediators. Therefore, Id2 may provide an important target of neuropathic pain treatment.

摘要

DNA结合/分化抑制因子2(Id2)属于螺旋-环-螺旋蛋白家族。最近的研究表明,Id2在神经元存活和神经保护中起关键作用。然而,在神经性疼痛条件下,Id2的作用仍不清楚。在本研究中,我们在大鼠慢性压迫损伤(CCI)模型中研究了Id2对神经性疼痛的影响。我们的结果表明,Id2在CCI大鼠的背根神经节(DRG)中呈时间依赖性上调。鞘内注射短发夹RNA(shRNA)-Id2可减轻CCI大鼠的机械性异常性疼痛和热痛觉过敏,并抑制CCI大鼠DRG中TNF-α和IL-1β的表达。此外,敲低Id2可降低CCI大鼠DRG中NF-κB p65的表达。综上所述,我们的研究结果表明敲低Id2可能通过抑制NF-κB激活来抑制促炎介质的产生,从而减轻神经性疼痛。因此,Id2可能为神经性疼痛治疗提供一个重要靶点。

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本文引用的文献

1
Silencing of Id2 attenuates hypoxia/ischemia-induced neuronal injury via inhibition of neuronal apoptosis.Id2基因沉默通过抑制神经元凋亡减轻缺氧/缺血诱导的神经元损伤。
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Small interfering RNA-mediated knockdown of NF-κBp65 attenuates neuropathic pain following peripheral nerve injury in rats.
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Functional recovery after peripheral nerve injury is dependent on the pro-inflammatory cytokines IL-1β and TNF: implications for neuropathic pain.外周神经损伤后的功能恢复依赖于促炎细胞因子 IL-1β 和 TNF:对神经病理性疼痛的影响。
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The IKK-NF-kappaB pathway: a source for novel molecular drug targets in pain therapy?IKK-NF-κB信号通路:疼痛治疗中新分子药物靶点的来源?
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Id2 intrinsically regulates lymphoid and erythroid development via interaction with different target proteins.Id2通过与不同靶蛋白相互作用,内在地调节淋巴细胞和红细胞的发育。
Blood. 2008 Aug 15;112(4):1068-77. doi: 10.1182/blood-2008-01-133504. Epub 2008 Jun 3.
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Decreased ID2 promotes metastatic potentials of hepatocellular carcinoma by altering secretion of vascular endothelial growth factor.ID2降低通过改变血管内皮生长因子的分泌促进肝细胞癌的转移潜能。
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Neuropathic pain: redefinition and a grading system for clinical and research purposes.神经性疼痛:用于临床和研究目的的重新定义及分级系统。
Neurology. 2008 Apr 29;70(18):1630-5. doi: 10.1212/01.wnl.0000282763.29778.59. Epub 2007 Nov 14.