| 张铃,刘菲,曾建伟,赵春雨,熊晓满,林珊,黄彬,陈达鑫,林育鹏,蔡巧燕.基于网络药理学分析黄芩素降低血压和调控炎症的作用机制[J].实用中西医结合临床,2022,22(11): |
| 基于网络药理学分析黄芩素降低血压和调控炎症的作用机制 |
| Based on Network Pharmacology to Explore the Mechanism of Baicalein in the Treatment of Hypertension and Regulation of Inflammation |
| 投稿时间：2022-05-09 修订日期：2022-05-17 |
| DOI： |
| 中文关键词: 黄芩素 高血压 炎症 网络药理学 机制 |
| 英文关键词: Baicalein Hypertension Inflammation Network pharmacology Mechanism |
| 基金项目:福建省科技重大专项（编号：2019YZ014004），福建中医药大学校管课题（编号：X2021005，X2021017） |
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| 中文摘要: |
| 目的：探讨黄芩素对AngⅡ诱导的高血压小鼠的血压及血清中炎症相关因子表达的影响，并基于网络药理学进一步分析黄芩素治疗高血压的潜在作用机制。方法：利用AngⅡ皮下埋泵灌注的方式建立高血压小鼠模型，将24只C57BL/6小鼠随机分为对照组、AngⅡ组、AngⅡ+黄芩素组。黄芩素每天灌胃剂量为5 mg/kg/天，对照组和AngⅡ组给予等体积生理盐水灌胃，连续干预4周。利用鼠尾无创血压仪每周监测各组小鼠血压；利用Bio-plex试剂盒检测各组小鼠血清中炎症相关因子的表达。同时，运用ETCM、TCMSP数据库筛选黄芩素的作用靶点基因；再运用Disgenet、OMIM等数据库筛选高血压疾病相关的靶点基因，对两者取交集，并利用KEGG进行通路富集分析。结果：AngⅡ组第1-4周的收缩压、舒张压及平均动脉压均显著高于对照组（P<0.05）；黄芩素干预2周后，能显著抑制AngⅡ诱导的高血压小鼠收缩压、舒张压及平均动脉压的升高（P<0.05）；与对照组比较，AngⅡ组小鼠血清中的IL-6，MCP-1，TNF-α，IL-1α，MIP-1α，RANTES的含量均显著升高（P<0.05），而IL-10的含量则显著降低（P<0.05）；黄芩素干预后，则能显著降低AngⅡ诱导的高血压小鼠血清中IL-6，MCP-1的含量（P<0.05），升高IL-10的含量（P<0.05），但对TNF-α，IL-1α，MIP-1α，RANTES的含量没有影响（P>0.05）。同时，挖掘出的黄芩素潜在作用靶点基因共有72个、高血压相关靶点基因共有9032，两者的交集靶点基因为58个。基于KEGG通路富集分析提示其与代谢途径、氮代谢、JAK-STAT信号通路、PI3K-AKT信号通路、趋化因子信号通路等密切相关。结论：黄芩素能显著抑制AngⅡ诱导的高血压小鼠的血压升高，调控血清中炎症相关因子的表达，其可能的作用机制与调控代谢途径、氮代谢、JAK-STAT信号通路、PI3K-AKT信号通路、趋化因子信号通路等有关。 |
| 英文摘要: |
| Objective: To investigate the effects of baicalein on the elevated blood pressure and the levels of inflammation-related factors in serum of AngⅡ-induced hypertensive mice, and to further analyze the potential mechanism of baicalein in the treatment of hypertension based on network pharmacology. Methods: The hypertensive mouse model was established by injecting AngⅡ into mice with subcutaneous Mini-osmotic pump (model:2004). All the mice were randomly divided into three groups: Control, AngⅡ, AngⅡ+baicalein. Mice in the AngⅡ+baicalein group were daily treated 5 mg/kg/day baicalein by intragastrical administration. Mice in Control and AngⅡ groups were daily received the equal volumes of saline. The blood pressure of mice in each group was measured by using the tail-cuff plethysmograph method every week. And the levels of inflammation-related factors in serum of each group were detected using bioplex assay kit. Meanwhile, the potential target genes of baicalein were screened via ETCM and TCMSP databases. Then, the hypertensive target genes were found in Disgenet, OMIM and other databases. Subsequently, the intersection of baicalein’s target genes and hypertension-related target genes was obtained and pathway enrichment analysis was further performed by KEGG. Results: Systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) of mice in AngⅡ group were significantly higher than those in Control group at week 1-4 (P<0.05). Following the treatment of baicalein for two weeks, the elevated SBP, DBP and MAP in AngⅡ-induced hypertensive mice were all significantly decreased (P<0.05). Compared with Control group, the levels of IL-6, MCP-1, TNF-α, IL-1α, MIP-1α and RANTES in serum of mice in AngⅡ group were significantly increased (P<0.05), while the level of IL-10 was significantly decreased (P<0.05). After treatment with baicalein, the levels of IL-6 and MCP-1 were significantly decreased (P<0.05) and the level of IL-10 was significantly increased (P<0.05) in serum of AngⅡ-induced hypertensive mice. However, there were no obviously difference on the levels of TNF-α, IL-1α, MIP-1α and RANTES between the AngⅡ group and AngⅡ+baicalein group (P>0.05). Moreover, 72 potential target genes of baicalein and 9032 hypertension-related target genes were found, and the intersection on both of target genes was 58. And KEGG pathway enrichment analysis suggested that baicalein treatment of hypertension was closely related to metabolic pathways, nitrogen metabolism, JAK-STAT signaling pathway, PI3K-AKT signaling pathway, chemokine signaling pathway and so on. Conclusions: Baicalin can significantly inhibit the elevated blood pressure, regulate the levels of inflammation-related factors in serum of AngⅡ-induced hypertensive mice. The possible mechanism of baicalin is associated with the regulation of metabolic pathways, nitrogen metabolism, JAK-STAT signaling pathway, PI3K-AKT signaling pathway, chemokine signaling pathway. |
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