枢经推拿通过m6A甲基转移酶METTL3调控SOCS-1/TLR4通路抑炎镇痛的机制研究

我们前期研究发现m6A甲基转移酶METTL3、TLR4、炎症因子与疼痛相关，又分别证实推拿能通过下调METTL3、TLR4和炎症因子达到镇痛效果。有文献指出，在naive T细胞中敲除METTL3可增加SOCS-1表达，SOCS-1对TLR4有调控作用，但在疼痛中METTL3、SOCS-1、TLR4、炎症因子是否存在级联关系尚需进一步研究。据此提出假说，推拿可能通过影响m6A甲基转移酶METTL3，调控SOCS-1/TLR4活化，抑制炎症因子释放，达到镇痛作用。本研究建立疼痛大鼠模型，开展以下研究：①观察推拿后大鼠热痛阈和机械痛阈以明确推拿镇痛效果；②检测NPP大鼠m6A丰度、METTL3、SOCS-1、TLR4、NF-κB、IL-6的表达，以及沉默METTL3后上述指标的表达以阐明疼痛传递机制。③明确推拿镇痛的效应机制。本研究从表观遗传学揭示疼痛发生机制，为阐明推拿镇痛机制提供新思路。

We have found that massage can effectively relieve pain, and confirmed that massage can down regulate m6A methyltransferase METTL3 and down regulate TLR4 cascade to inhibit the release of inflammatory factors. Studies have shown that knocking out METTL3 can increase SOCS-1 expression and SOCS-1 can regulate TLR4. Based on this hypothesis, massage may influence METTL3, to regulate the activation of SOCS-1/TLR4, inhibiting the release of inflammatory factors to achieve analgesic effect. We plan to establish a rat model of pain and carry out following study:(1) to observe the thermal pain threshold and mechanical pain threshold of rats after massage to clarify the analgesic effect of massage; (2) to detect the abundance of m6A, the expression of METTL3,SOCS-1,TLR4,NF-κB、IL-6 and the expression of the above indicators after METTL3 silencing in NPP rats to clarify the mechanism of pain transmission. (3) to clarify the mechanism of massage analgesia. This study reveals the mechanism of pain from epigenetics and provides new ideas to elucidate the mechanism of massage analgesia.