蒙医三根平衡针法对慢性应激抑郁模型大鼠海马miRNA表达谱的影响

Effects of Mongolian medicine's three-balanced acupuncture on miRNA expression profile of hippocampus in chronic stress depressed rats

目的:观察蒙医三根平衡针法对慢性不可预知温和应激刺激(CUMS)抑郁模型大鼠海马miRNA表达谱的影响,探讨蒙医三根平衡针法治疗抑郁症的作用机制。方法:利用miRNA芯片技术检测正常组、模型组、药物组和蒙医针组大鼠海马miRNA差异表达变化,利用生物信息软件进行靶基因预测及差异表达miRNA趋势分析,并分别构建差异表达miRNA与靶基因、基因显著性功能(GO)和显著性通路(Pathway)的网络,分析蒙医三根平衡针法治疗抑郁症主导作用的基因功能与通路。结果:经miRNA芯片技术检测4组样品中筛选出显著性差异表达65条miRNA(P<0.05,FC>1.2),121个GO(P<0.01)和85个通路(P<0.05)。趋势分析获得2个显著性趋势模式(P<0.05),差异表达miRNA与靶基因网络中Nlgn1、Clock、Per3、Plin2、Tarbp1、Abca9、Adamts2等基因与差异表达miRNA的关系强度最显著,miRNA-GO网络中差异表达miRNA与神经发育、生物节律过程、光刺激的反应等生物学功能的作用关系最明显,miRNA-Pathway网络中轴突导向、神经营养因子通路、昼夜节律、多巴胺能突触、谷氨酸能突触等通路的作用关系最强。3个调控网络中miR-29b-3p均处于网络的枢纽性地位。结论:CUMS和蒙医三根平衡针法均改变了大鼠海马miRNA表达谱,蒙医三根平衡针法的抗抑郁作用机制可能与其调节miR 29b-3p靶向调控Nlgn1和生物节律基因Clock、Per3的表达有关。

Objective: To observe the effects of Mongolian medicine three-balanced acupuncture on miRNA expression profile of hippocampus in chronic stress depression model rats, and to explore the mechanism of Mongolian medicine threebalanced acupuncture to treat depression. Methods: The miRNA chip technology was used to detect the differential expression of miRNA in the hippocampus of normal group, model group, drug group and Mongolian acupuncture group. The target genes were predicted and the differentially expressed miRNA trend was analyzed using bioinformatics software. Construct the miRNA target gene network, the miRNA target GO network and the miRNA target pathway network, the gene functions and pathways of Mongolian medicine’s three-balanced acupuncture methods for the treatment of depression were analyzed. Results: A total of 65 miRNA(P<0.05, FC>1.2), 121 GO(P<0.01), and 85 pathway(P<0.05) were detected in the 4 groups of samples by miRNA chip technology. Trend analysis obtained two significant trend patterns(P<0.05). Differentially expressed miRNA and Nlgn1, Clock, Per3, Plin2, Tarbp1, Abca9, Adamts2 and other genes in the target gene network had the most significant relationship with differentially expressed miRNA, miRNA-differentially expressed miRNA in the GO network had the most obvious relationship with biological functions such as neural development, biological rhythmic processes, and response to light stimuli. In the miRNApathway network, axon guidance, neurotrophic factor pathways, circadian rhythms, dopaminergic synapses. The role of glutamate synaptic pathways was strongest, and miR-29 b-3 p was in the pivotal position of the three regulatory networks. Conclusion: Both CUMS and Mongolian medicine’s three-balanced acupuncture have changed the expression profile of rat hippocampus miRNA. The antidepressant mechanism of Mongolian medicine’s three-balanced acupuncture may be related to its regulation of miR-29 b-3 p and targeted regulation of Nlgn1 and biological rhythm genes Clock and Per3 Related expressions.