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鞘内注射短发夹 RNA 沉默 NMDA 受体 NR2B 亚单位减少 C57BL/6 小鼠福尔马林诱导的疼痛。

Gene silencing of NR2B-containing NMDA receptor by intrathecal injection of short hairpin RNA reduces formalin-induced nociception in C57BL/6 mouse.

机构信息

Department of Anesthesiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.

出版信息

Int J Neurosci. 2013 Sep;123(9):650-6. doi: 10.3109/00207454.2013.789873. Epub 2013 May 9.

DOI:10.3109/00207454.2013.789873
PMID:23528046
Abstract

Spinal NR2B-containing N-methyl-D-aspartate receptors (NR2B) play a critical role in the formation of central sensitization and persistent pain. Previous studies show that gene silencing of the spinal NR2B subunit by small interfering RNA (siRNA) could alleviate nociception in animals. The siRNA is a 19- to 23-nt RNA duplex, which can be synthesized in vitro or derived from short hairpin RNAs (shRNAs). In the present study, we investigated whether intrathecal injection of shRNAs targeting NR2B (GRIN2B shRNA) could affect nociception on formalin-induced pain in mice. Our results showed that intrathecal injection of GRIN2B shRNA could decrease NR2B mRNA and protein expression levels and hence effectively relieve formalin-induced nociception in mice, suggesting that intrathecal delivery of GRIN2B shRNA can be an efficient way to silence the target gene and provide new insights into the treatment of chronic pain.

摘要

脊髓 NR2B 含量 N-甲基-D-天冬氨酸受体(NR2B)在中枢敏化和持续性疼痛的形成中起着关键作用。先前的研究表明,通过小干扰 RNA(siRNA)对脊髓 NR2B 亚基进行基因沉默可以减轻动物的痛觉。siRNA 是一种 19 到 23 个核苷酸的 RNA 双链体,可在体外合成或源自短发夹 RNA(shRNA)。在本研究中,我们研究了鞘内注射靶向 NR2B 的 shRNA(GRIN2B shRNA)是否会影响小鼠福尔马林诱导疼痛的痛觉。我们的结果表明,鞘内注射 GRIN2B shRNA 可以降低 NR2B mRNA 和蛋白质表达水平,从而有效缓解小鼠福尔马林诱导的痛觉,表明鞘内递送 GRIN2B shRNA 可以是沉默靶基因的有效方法,并为慢性疼痛的治疗提供新的见解。

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