Lu Shan, Ma Sichao, Wang Yunyun, Huang Tao, Zhu Zhihua, Zhao Guoqing
Department of Anesthesia, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Department of Nephrology, The First Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, Jilin 130021, P.R. China.
Mol Med Rep. 2017 Jul;16(1):353-360. doi: 10.3892/mmr.2017.6559. Epub 2017 May 10.
Neuropathic pain is a nerve disorder characterized by the dysregulation of ion channels in dorsal root ganglion (DRG) neurons. MicroRNAs (miRs) may be associated with the molecular mechanisms underlying the altered levels of ion channels; however, the molecular mechanisms remain widely unknown. To investigate these mechanisms, the present study conducted a genomic analysis of miR between a unilateral spared nerve injury (SNI) model and sham control. Differentially expressed miRs between the SNI and sham groups were selected for transfection of DRG cells, a polymerase chain reaction (PCR) array analysis was subsequently performed. A total of three significantly differently expressed genes were selected from the results of the PCR array and further analyzed by reverse transcription‑quantitative PCR. Genomic analysis revealed that Mus musculus miR‑449a (mmu‑miR‑449a) was reduced in the SNI groups compared with the sham controls. The PCR array indicated that mmu‑miR‑449a‑transfection reduced the mRNA expression levels of transient receptor potential cation channel subfamily A member 1 (TRPA1), and calcium‑activated potassium channel subunit α‑1 (KCNMA1) and increased the level of transmembrane phosphatase with tension homology (TPTE) in the DRG cells (P<0.05). qRT‑PCR analysis further indicated that mmu‑miR‑449a transfection caused similar alterations in the mRNA expression levels of TRPA1, KCNMA1 and TPTE in DRG cells, respectively (P<0.05). Therefore, mmu‑miR‑449a may ameliorate neuropathic pain by decreasing the activity of the channel proteins TRPA1 and KCNMA1 and increasing the levels of TPTE. mmu‑miR‑449a may be a potential therapeutic molecule for the alleviation of neuropathic pain.
神经性疼痛是一种神经紊乱疾病，其特征为背根神经节（DRG）神经元中的离子通道失调。微小RNA（miR）可能与离子通道水平改变的潜在分子机制有关；然而，其分子机制仍大多未知。为了研究这些机制，本研究对单侧坐骨神经分支选择性损伤（SNI）模型和假手术对照组之间的miR进行了基因组分析。选择SNI组和假手术组之间差异表达的miR转染DRG细胞，随后进行聚合酶链反应（PCR）阵列分析。从PCR阵列结果中总共选择了三个差异显著表达的基因，并通过逆转录-定量PCR进一步分析。基因组分析显示，与假手术对照组相比，SNI组中小鼠miR-449a（mmu-miR-449a）水平降低。PCR阵列表明，mmu-miR-449a转染降低了DRG细胞中瞬时受体电位阳离子通道亚家族A成员1（TRPA1）和钙激活钾通道亚基α-1（KCNMA1）的mRNA表达水平，并增加了张力同源性跨膜磷酸酶（TPTE）的水平（P<0.05）。qRT-PCR分析进一步表明，mmu-miR-449a转染分别导致DRG细胞中TRPA1、KCNMA1和TPTE的mRNA表达水平发生类似变化（P<0.05）。因此，mmu-miR-449a可能通过降低通道蛋白TRPA1和KCNMA1的活性以及增加TPTE的水平来改善神经性疼痛。mmu-miR-449a可能是缓解神经性疼痛的潜在治疗分子。
