miR-212-3p靶向MeCP2调节BDNF/TrkB通路对神经病理性疼痛的影响  

The Effect of miR-212-3p Targeting MeCP2 on the Regulation of BDNF/TrkB Pathway on Neuropathic Pain

作　　者：赵辉 梁雪 王玲[2] 杨少杰 丰晖 ZHAO Hui;LIANG Xue;WANG Ling;YANG Shaojie;FENG Hui(The Second People's Hospital of Gansu Province,Lanzhou 730000,China;不详)

机构地区：[1]甘肃省第二人民医院,甘肃兰州730000 [2]兰州大学第一医院

出　　处：《中外医学研究》2025年第6期142-146,共5页CHINESE AND FOREIGN MEDICAL RESEARCH

基　　金：甘肃省自然科学基金项目(22JR5RA737)。

摘　　要：目的:探讨miR-212-3p介导BDNF/TrkB靶向MeCP2表观遗传修饰在神经病理性疼痛中发挥的作用。方法:将SD大鼠分为3组:空白对照组(Black组),假手术组(Sham组),慢性缩窄性损伤组(CCI组)。术后1 d监测大鼠的机械缩足阈值(PWMT)和热缩足潜伏期(PWTL),并通过RT-PCR检测脊髓组织miR-212-3p、MeCP2、脑源性神经营养因子(BDNF)和TrkB mRNA的表达,Western Blot检测大鼠脊髓组织MeCP2、BDNF和TrkB蛋白的含量。体外miR-212-3p过表达质粒转染脊髓神经元DRG细胞,RT-PCR和Western Blot分别检测MeCP2、BDNF、TrkB的m RNA和蛋白的表达。结果:CCI组出现甩足、舔足、足趾并拢等行为学异常;与Sham组比较,大鼠PMWT和PWTL值均下降,差异有统计学意义(P<0.05);脊髓组织miR-212-3p表达表达上调,MeCP2的mRNA及蛋白表达下调,而BDNF和TrkB的m RNA及蛋白的表达均上调,差异有统计学意义(P<0.05)。与Black组比较,miR-212-3p mimic组细胞MeCP2 mRNA和蛋白的表达下降,而BDNF和TrkB的m RNA及蛋白表达均显著上调,差异有统计学意义(P<0.05);与Black组比较,miR-212-3p inhibitor组的上述指标结果相反,差异有统计学意义(P<0.05)。结论:miR-212-3p的抑制可以上调MeCP2,从而通过MeCP2表观遗传修饰下调BDNF/TrkB通路,缓解神经病理性疼痛。Objective:To investigate the role of miR-212-3p-mediated epigenetic modification of BDNF/TrkB targeting MeCP2 in neuropathic pain in vitro and in vivo.Method:SD rats were divided into 3 groups:blank control group(Black group),Sham group(Sham group)and chronic constriction injury group(CCI group).The paw withdrawal mechanical threshold(PWMT)and paw withdrawal thermal latency(PWTL)of rats were monitored one day after surgery,and the mRNA expressions of miR-212-3p,MeCP2,brain-derived neurotrophic factor(BDNF)and TrkB in spinal cord tissues were detected by RT-PCR.The content of MeCP2,BDNF and TrkB proteins in rat spinal cord were detected by Western Blot.In vitro miR-212-3p overexpression plasmid was transfected into spinal cord neuronal DRG cells,and the mRNA and protein expressions of MeCP2,BDNF and TrkB were detected by RT-PCR and Western Blot,respectively Result:In CCI group,there were some behavioral abnormalities,such as flapping feet,licking feet and drawing toes together.Compared with Sham group,PMWT and PWTL values were decreased,and the difference was statistically significant(P<0.05).The expression of miR-212-3p was up-regulated,the mRNA and protein expressions of MeCP2 were down-regulated,while the mRNA and protein expressions of BDNF and TrkB were up-regulated,with statistical significance(P<0.05).Compared with the Black group,the expression of MeCP2 mRNA and protein of miR-212-3p mimic cells decreased,while the expression of BDNF and TrkB mRNA and protein were significantly up-regulated(P<0.05).Compared with Black group,the above index results of miR-212-3p inhibitor group were opposite(P<0.05).Conclusion:Inhibition of miR-212-3p can up-regulate MeCP2,thereby down-regulating BDNF/TrkB pathway through MeCP2 epigenetic modification and relieving neuropathic pain.

关 键 词：MECP2 神经病理性疼痛 BDNF/TrkB miR-212-3p 表观遗传学 

分 类 号：R74[医药卫生—神经病学与精神病学]