当归挥发油对自发性高血压大鼠心肌组织中微小 RNA差异表达谱的影响

摘要

目的：探讨当归挥发油对自发性高血压大鼠（SHRs）心肌组织中微小 RNA （miRNA）表达谱的影响，阐明当归挥发油发挥作用的可能机制。方法：将 SHRs 分为模型组、卡托普利组和当归组，取同周龄的正常 Wistar 大鼠作为对照组，采用无创套尾法测定大鼠尾动脉收缩压，给药4周后，采用 Affymetrix miRNA 4.0芯片测定心肌组织中 miRNA 表达谱，采用京东基因与基因组百科全书（KEGG）富集法分析差异表达的miRNA 靶基因。结果：给药前模型组大鼠收缩压明显高于对照组（P ＜0.05），连续服药1～4周后，卡托普利组和当归组大鼠收缩压明显低于模型组（P ＜0.05）。与模型组比较，当归组大鼠差异表达的 miRNA 29个，其中表达上调的 miRNA 13个（Ratio＞2.0，P ＜0.05），表达下调的 miRNA 16个（Ratio ＜0.5，P ＜0.05）。KEGG 富集分析，miR-19a、let-7i 和 miR-181c 与胰岛素信号通路有关联（P ＜0.05），let-7i 、miR-181a 和miR-455与血管内皮生长因子（VEGF）信号通路调控有关联（P ＜0.05），miR-122、miR-181a、miR-200b、miR-181c、let-7i 和 miR-19a 与细胞凋亡有关联（P ＜0.05）。结论：当归挥发油可降低 SHRs 血压，对 SHRs 心肌组织中 miRNA 表达谱产生影响，可能通过调节胰岛素信号通路及 VEGF 信号通路相关 miRNA 发挥血压调节作用。%Objective:To explore the effect of Angelica Sinensis Volatile Oil on the mi RNA expression profiling in myocardium tissue of the spontaneously hypertensive rats (SHRs),and to clarify the possible mechanism of Angelica Sinensis Volatile Oil.Methods:All the SHRs were divided into Angelica group,model group and captopril group,and other Wistar rats with the same age were selected as control group.The non-invasive systolic blood pressure was detected;after 4 weeks of administration,the changes of miRNA expression profiling in myocardium tissue were measured by Affymetrix miRNA 4.0 Array.KEGG analysis was used to identify the target genes. Results:Compared with control group,the systolic blood pressure of the rats in model group was significantly decreased (P < 0.05)before treatment.4 weeks after administration,compared with model group,the systolic blood pressure of the rats in Angelica group was significantly decreased (P <0.05).Compared with model group, 29 differential miRNAs of rats in Angelica group were found (P < 0.05 ), with 13 up-regulated miRNAs and 16 down-regulated miRNAs.The KEGG analysis results showed that miR-19a,let-7i,and miR-181c were related to insulin signaling pathways; let-7i, miR-181a, and miR-455 were related to VEGF signaling pathways;miR-122,miR-181a, miR-200b, miR-181c, let-7i, and miR-19a were related to apoptosis (P < 0.05 ). Conclusion:Angelica Sinensis Volatile Oil can decrease the blood pressure in SHRs and it can regulate the blood pressure by regulating the miRNA related to insulin signaling pathways and VEGF signaling pathways.