Department of Anesthesia, Zhejiang Taizhou Hospital Affiliated to Wenzhou Medical University, Taizhou 317000, China.
Department of Anesthesia, Zhejiang Taizhou Hospital Affiliated to Wenzhou Medical University, Taizhou 317000, China.
Brain Res Bull. 2017 Oct;135:1-7. doi: 10.1016/j.brainresbull.2017.09.004. Epub 2017 Sep 9.
Anesthetic reagents, such as bupivacaine (Bv), induce significant neurotoxicity in dorsal root ganglion neurons (DRGNs). In this study, we investigated the expression, function and cross-association of microRNA-137-3p (miR-137-3p) and lysine (K)-specific demethylase 1A (LSD1) in a murine model of Bv-induced neural injury in DRGNs.
Murine DRGNs were culture in vitro and treated with Bv. QPCR was used to evaluate miR-137-3p expression in Bv-injured DRGNs. MiR-137-3p was genetically downregulated to evaluate its rescuing effect on Bv-induced DRGN apoptosis and neurite retraction. The association of miR-137-3p on its downstream target, LSD1 coding gene KDM1A, was evaluated by dual-luciferase activity assay and qPCR. In miR-137-3p-downregulated DRGNs, KDM1A was inhibited to evaluate its involvement in miR-137-3p-mediated modulation on Bv-induced DRGN neurotoxicity. Furthermore, KDM1A expression in Bv-injured DRGN was evaluated by qPCR, and LSD1 was overexpressed in DRGN to evaluate its direct effect on Bv-induced neurotoxicity.
MiR-137-3p was upregulated in Bv-injured DRGNs. MiR-137-3p downregulation rescued Bv-induced DRGN apoptosis and neurite retraction. LSD1 was demonstrated to be downstream to, and inversely modulated by miR-137-3p in DRGN. In Bv-injured DRGNs, LSD1 downregulation reversed miR-137-3p-downregualtion-induced neural protection. Furthermore, LSD1 upregulation directly rescued Bv-induced apoptosis and neurite retraction in DRGNs.
MiR-137-3p and its downstream target LSD1 are inversely associated to regulate anesthetics-induced neurotoxicity in DRGN. This signaling pathway may be a therapeutic candidate to reduce anesthetics-induced neurological damage in human patients.
布比卡因（Bv）等麻醉剂会引起背根神经节神经元（DRGN）产生显著的神经毒性。在这项研究中，我们在 Bv 诱导的 DRGN 神经损伤的小鼠模型中，研究了 microRNA-137-3p（miR-137-3p）和赖氨酸（K）特异性去甲基酶 1A（LSD1）的表达、功能和相互关联。
在体外培养小鼠 DRGN 并进行 Bv 处理。QPCR 用于评估 Bv 损伤的 DRGN 中 miR-137-3p 的表达。通过基因下调 miR-137-3p 来评估其对 Bv 诱导的 DRGN 凋亡和轴突回缩的挽救作用。通过双荧光素酶活性测定和 qPCR 评估 miR-137-3p 对其下游靶基因 LSD1 编码基因 KDM1A 的关联。在下调 miR-137-3p 的 DRGN 中，抑制 KDM1A 以评估其在 miR-137-3p 介导的 Bv 诱导的 DRGN 神经毒性调节中的作用。此外，通过 qPCR 评估 Bv 损伤的 DRGN 中的 KDM1A 表达，并在 DRGN 中过表达 LSD1 以评估其对 Bv 诱导的神经毒性的直接作用。
miR-137-3p 在 Bv 损伤的 DRGN 中上调。下调 miR-137-3p 挽救了 Bv 诱导的 DRGN 凋亡和轴突回缩。LSD1 被证明是 DRGN 中的下游靶标，并受 miR-137-3p 的反向调节。在 Bv 损伤的 DRGN 中，下调 LSD1 逆转了 miR-137-3p 下调诱导的神经保护作用。此外，LSD1 的上调直接挽救了 Bv 诱导的 DRGN 中的凋亡和轴突回缩。
miR-137-3p 和其下游靶标 LSD1 呈负相关，调节麻醉剂诱导的 DRGN 神经毒性。该信号通路可能是减少人类患者中麻醉剂引起的神经损伤的治疗候选物。
