METTL3调控G9a的甲基化修饰参与瑞芬太尼诱发术后痛觉过敏的机制研究

瑞芬太尼诱发术后痛觉过敏(RIH)发生率高且机制不明。我们发现Ehmt2(G9a mRNA)甲基化(m6A)水平上调可导致痛阈降低(Advanced Science，IF：15.804)。前期研究发现瑞芬太尼输注后引起METTL3降低，继而Ehmt2的m6A水平降低，且G9a蛋白增多可下调Slack表达。然而具体的表观遗传学分子机制尚不明确，由此提出METTL3-G9a-Slack通路参与RIH机制的假说。本课题在前期研究基础上，拟采用m6A-eCLIP-seq assay、m6A-RIP、RIP和膜片钳等方法，从表观遗传学的角度深入探讨背根神经节中RNA组的m6A修饰变化、METTL3调控Ehmt2的m6A修饰的具体位点，以及METTL3-G9a调控Slack通道的组蛋白修饰位点和神经电生理学变化在RIH中的作用，为RIH提供新的理论支持和临床防治思路。

Remifentanil-induced postoperative hyperalgesia (RIH) has a high incidence and the mechanism is still elusive. We found that up-regulation of Ehmt2(G9a mRNA) methylation(m6A) level can lead to a reduction in pain threshold(Advanced Science, IF: 15.804). Earlier studies found that remifentanil infusion caused a decrease in METTL3, followed by a decrease in m6A level of Ehmt2, and an increase in G9a protein can down-regulate Slack expression. However, the specific molecular mechanism of epigenetics is not clear, therefore, the hypothesis of METTL3-G9a-Slack pathway involved in the RIH mechanism is proposed. Based on the previous research, this project intends to use the methods such as m6A-eCLIP-seq assay, m6A-RIP, RIP and patch-clamp recording, from the perspective of epigenetics to explore the changes in m6A modification of the RNA group in dorsal root ganglia, METTL3 regulates the specific site of m6A modification of Ehmt2, and METTL3-G9a regulates the histone modification sites and neuroelectrophysiological changes of Slack channels in RIH, providing new theoretical support and clinical prevention ideas for RIH.