Temporal Changes of Spinal Transcriptomic Profiles in Mice With Spinal Nerve Ligation
Temporal Changes of Spinal Transcriptomic Profiles in Mice With Spinal Nerve Ligation
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DOI：
10.3389/fnins.2019.01357
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发表时间：
2019-12
影响因子：
4.3
通讯作者：
Hong-Mei Yu;Piao Zhang;Yeru Chen;Yong-Jie Wang;Xianyi Lin;Xiang-Yao Li;Gang Chen
中科院分区：
文献类型：
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作者：
Hong-Mei Yu;Piao Zhang;Yeru Chen;Yong-Jie Wang;Xianyi Lin;Xiang-Yao Li;Gang Chen
神经病理性疼痛(NP)是一种伴有痛觉异常、痛觉过敏和自发性疼痛的顽固性疾病。越来越多的证据表明，大量的神经递质、基因和信号通路与NP的发生和发展有关，但其潜在的机制仍不清楚。因此，进一步阐明制定适当治疗方案的潜在调控网络是极其重要的。在这里，RNA-Seq高通量测序被用来确定脊神经结扎(SNL)小鼠的基因表达变化。同时，利用综合差异表达与通径分析(IDEP)工具和字符串数据库对差异表达基因(DEG)进行分析。采用实时定量聚合酶链式反应(qRT-PCR)检测HUB基因的表达。结果表明，术后7d，差异表达基因主要由1712个上调基因和1515个下调基因组成，术后28d主要由243个上调基因和357个下调基因组成。此外，133个基因和逆行内源性大麻素信号和心肌收缩两条通路共同参与了术后第7天和第28天的生物反应。与Sham-7/28d组比较，SNL-7/28d组CCL5、Cacna 2d1、Cacna 2d2、CACNB2、GABRB3、GluA1和GluA2的mRNA和蛋白表达显著上调(SNL-7d比Sham-7d；SNL-28d比Sham-28d；P<；0.05)。SNL-7d组Glra2、Glra4、Glra3、Grik1、Grik2、NR1、NR2a、NR2B水平较Sham-7d组明显升高(P<；0.05)，但与Sham-28d组比较差异无统计学意义。因此，这些结果为深入阐明NP的潜在机制和确定治疗NP的关键因素提供了新的视角和策略。
Neuropathic pain (NP) is an intractable disease accompanying with allodynia, hyperalgesia and spontaneous pain. Accumulating evidence suggested that large volume of neurotransmitters, genes, and signaling pathways were implicated with the initiation and development of NP, while the underlying mechanism still remained poorly understood. Therefore, it was extremely important to further elucidate the potential regulatory networks for developing appropriate treatment options. Here, the RNA-Seq high-throughput sequencing was employed to determine the genes expression change in mice undergoing spinal nerve ligation (SNL). Meanwhile, the differentially expressed genes (DEGs) were analyzed by using integrated Differential Expression and Pathway analysis (iDEP) tools and String database. Then, quantitative real-time PCR (qRT-PCR) was employed to detect the expression of hub gens. The results showed that the DEGs mainly comprised 1712 upregulated and 1515 downregulated genes at 7 days, and consisted of 243 upregulated and 357 downregulated genes at 28 days after surgery, respectively. Additionally, 133 genes and two pathways including retrograde endocannabinoid signaling and cardiac muscle contraction collectively participated in biological reactions of 7th and 28th day after operation. Moreover, the results showed that the mRNA and protein expression of Ccl5, Cacna2d1, Cacna2d2, Cacnb2, Gabrb3, GluA1, and GluA2 were significantly upregulated in SNL-7/28d group than that of in Sham-7/28d group (SNL-7d vs. Sham-7d; SNL-28d vs. Sham-28d; P < 0.05). And the level of Glra2, Glra4, Glra3, Grik1, Grik2, NR1, NR2A, and NR2B was obviously increased in SNL-7d group compared to Sham-7d group (P < 0.05), but which was no statistical difference between SNL-28d group and Sham-28d group. Therefore, these results provided new perspectives and strategies for deeply illuminating the underlying mechanism, and identifying the key elements for treating NP.