Department of Anesthesiology, Jining First People's Hospital, Jining, 272100, China.
Department of Anesthesiology, Jining First People's Hospital, Jining, 272100, China.
Biomed Pharmacother. 2016 Aug;82:298-303. doi: 10.1016/j.biopha.2016.04.042. Epub 2016 May 18.
Long non-coding RNA IGF2AS was initially identified as a cancer regulator in wilm's tumors. In this study, IGF2AS was investigated of its functions in inducing neural development and protecting local-anesthetic induced neurotoxicity in dorsal root ganglion (DRG) in spinal cord.
Explant of mouse spinal cord DRG was transfected with IGF2AS specific siRNA. The effect of IGF2AS inhibition on neural development was assessed by neurite growth assay, qRT-PCR and western blot assay, respectively. IGF2AS-downregulated DRG explant was then exposed to local anesthetic agent, lidocaine in vitro. The possible protective effects of IGF2AS inhibition on lidocaine-induced DRG neuron apoptosis and neurite loss were further assessed by TUNEL assay, neurite growth assay, qRT-PCR and western blot assays.
SiRNA-mediated IGF2AS inhibition promoted neuronal growth, and induced IGF2, BDNF and NT3 upregulations at both gene and protein expressions. In lidocaine-exposed DRG neurons, endogenous IGF2AS inhibition was effective to protect local-anesthetic induced neuronal apoptosis and neurite loss. Further molecular characterization demonstrated that the neuronal protection of IGF2AS inhibition was also associated with upregulations of IGF2, BDNF and NT3 in DRG neurons.
Inhibiting endogenous IGF2AS may promote neuronal growth and protect local-anesthetic induced neurotoxicity in DRG neurons, possibly through complimentary IGF2 upregulation and autocrine activation neurotrophin genes.
长链非编码 RNA IGF2AS 最初在威尔姆氏肿瘤中被鉴定为一种癌症调控因子。在这项研究中，研究了 IGF2AS 在诱导脊髓背根神经节（DRG）神经发育和保护局部麻醉剂诱导的神经毒性中的作用。
用 IGF2AS 特异性 siRNA 转染小鼠脊髓 DRG 外植体。通过神经突生长测定、qRT-PCR 和 Western blot 测定分别评估 IGF2AS 抑制对神经发育的影响。然后将 IGF2AS 下调的 DRG 外植体暴露于局部麻醉剂利多卡因体外。通过 TUNEL 测定、神经突生长测定、qRT-PCR 和 Western blot 测定进一步评估 IGF2AS 抑制对利多卡因诱导的 DRG 神经元凋亡和神经突损失的可能保护作用。
siRNA 介导的 IGF2AS 抑制促进神经元生长，并在基因和蛋白表达水平诱导 IGF2、BDNF 和 NT3 的上调。在暴露于利多卡因的 DRG 神经元中，内源性 IGF2AS 抑制有效保护局部麻醉剂诱导的神经元凋亡和神经突损失。进一步的分子特征表明，IGF2AS 抑制的神经元保护还与 DRG 神经元中 IGF2、BDNF 和 NT3 的上调有关。
抑制内源性 IGF2AS 可能促进神经元生长并保护 DRG 神经元中局部麻醉剂诱导的神经毒性，可能通过互补的 IGF2 上调和自分泌激活神经营养因子基因。
