Department of Anesthesiology and Pain Medicine, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 Hubei, China.
Department of Orthopedics, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Oxid Med Cell Longev. 2021 Nov 29;2021:2492286. doi: 10.1155/2021/2492286. eCollection 2021.
In this study, we investigated whether chemical 6-hydroxydopamine (6-OHDA) stimuli caused cardiac sympathetic denervation (SD), and we analyzed gene expression profiles to determine the changes in the lncRNA/circRNAs-miRNA-mRNA network in the affected spinal cord segments to identify putative target genes and molecular pathways in rats with myocardial ischemia-reperfusion injury (MIRI). Our results showed that cardiac sympathetic denervation induced by 6-OHDA alleviated MIRI. Compared with the ischemia reperfusion (IR, MIRI model) group, there were 148 upregulated and 51 downregulated mRNAs, 165 upregulated and 168 downregulated lncRNAs, 70 upregulated and 52 downregulated circRNAs, and 12 upregulated and 11 downregulated miRNAs in the upper thoracic spinal cord of the SD-IR group. Furthermore, we found that the differential genes related to cellular components were mainly enriched in extracellular and cortical cytoskeleton, and molecular functions were mainly enriched in chemokine activity. Pathway analysis showed that the differentially expressed genes were mainly related to the interaction of cytokines and cytokine receptors, sodium ion reabsorption, cysteine and methionine metabolism, mucoglycan biosynthesis, cGMP-PKG signaling pathway, and MAPK signaling pathway. In conclusion, the lncRNA/circRNAs-miRNA-mRNA networks in the upper thoracic spinal cord play an important role in the preventive effect of cardiac sympathetic denervation induced by 6-OHDA on MIRI, which offers new insights into the pathogenesis of MIRI and provides new targets for MIRI.
在这项研究中，我们调查了化学物质 6-羟多巴胺（6-OHDA）刺激是否会导致心脏交感神经去神经（SD），并分析了基因表达谱，以确定受影响脊髓节段中长链非编码 RNA/环状 RNA-miRNA-mRNA 网络的变化，以鉴定心肌缺血再灌注损伤（MIRI）大鼠中的潜在靶基因和分子途径。我们的结果表明，6-OHDA 诱导的心脏交感神经去神经可减轻 MIRI。与缺血再灌注（IR，MIRI 模型）组相比，SD-IR 组大鼠上胸段脊髓中有 148 个上调和 51 个下调的 mRNAs、165 个上调和 168 个下调的 lncRNAs、70 个上调和 52 个下调的 circRNAs 以及 12 个上调和 11 个下调的 miRNAs。此外，我们发现与细胞成分相关的差异基因主要富集在外泌体和皮质细胞骨架中，分子功能主要富集在趋化因子活性中。通路分析表明，差异表达基因主要与细胞因子和细胞因子受体的相互作用、钠离子重吸收、半胱氨酸和蛋氨酸代谢、粘多糖生物合成、cGMP-PKG 信号通路和 MAPK 信号通路有关。总之，上胸段脊髓中的 lncRNA/环状 RNA-miRNA-mRNA 网络在 6-OHDA 诱导的心脏交感神经去神经对 MIRI 的预防作用中发挥重要作用，为 MIRI 的发病机制提供了新的见解，并为 MIRI 提供了新的治疗靶点。
