| 摘要: |
| [目的] 评价穿心莲内酯干预过量异丙肾上腺素（ISO）致心力衰竭小鼠的药效，运用网络药理学的方法预测其作用靶点并验证。[方法] 制备过量盐酸异丙肾上腺素诱导的心力衰竭小鼠模型，随机分为空白组、模型组、穿心莲内酯组、地高辛组。通过心脏超声、形态学与病理分析，评价各组小鼠心功能。采用生物信息学分析工具（BAT－MAN-TCM）预测药物靶点，运用实时荧光定量PCR法检测候选靶点mRNA水平。[结果] 与空白组比较，模型组小鼠射血分数（EF）、短轴缩短率（FS）和舒张早期二尖瓣血流速度与舒张晚期二尖瓣血流速度比值（E/A）显著降低（P<0.05），左室收缩末内径（LVIDs）显著增大（P<0.05），心肌细胞肥大，伴有血窦扩张和结缔组织增生，心肌组织羟甲基戊二酸单酰辅酶A还原酶（HMGCR，HMG-CoA还原酶）基因表达显著上调（P<0.05）。与模型组相比，穿心莲内酯组小鼠EF、FS和E/A显著升高（P<0.05），LVIDs显著降低（P<0.01），心肌细胞肥大减轻，心肌组织HMGCR基因表达显著下调（P<0.05）。[结论] 穿心莲内酯可以改善过量异丙肾上腺素诱导的心力衰竭，其机制可能与抑制HMG-CoA还原酶、调节胆固醇合成有关。 |
| 关键词: 穿心莲内酯 心力衰竭 网络药理学 机制 |
| DOI：10.11656/j.issn.1673-9043.2018.03.12 |
| 分类号:R285.5 |
| 基金项目:国家自然基金重点项目（81530100）；北京中医药大学杰出青年人才项目（2015-JYB-XYQ002）。 |
|
| Pharmacological effects and mechanisms of andrographolide on isoproterenol induced heart failure in mice |
|
ZHANG Huimin, REN Yinglu, LIU Jinying, XIE Xuan, WANG Qing, SU Congping, WANG Wei, GUO Shuzhen
|
|
School of Chinese Medicine, Beijing University of Traditional Chinese Medicine, Beijing 100029, China
|
| Abstract: |
| [Objective] To study on the efficacy of andrographolide on heart failure induced by isoproterenol (ISO) in mice, and investigated its mechanism by combing experimental validation with network pharmacological prediction.[Methods] Mice with heart failure, induced by ISO, were randomly divided into control group, model group, andrographolide group and digoxin group. The cardiac function of mice was analyzed by echocardiography, morphology and pathology. The target was predicted by bioinformatics analysis tool (BATMAN-TCM), and the mRNA level of potential target gene was detected by real-time fluorescence quantitative PCR.[Results] Compared with the control group, EF, FS and E/A were significantly decreased in model group (P<0.05), LVIDs was significantly increased (P<0.05), cardiomyocyte hypertrophy, accompanied by sinus dilatation and connective tissue hyperplasia was observed, and the expression of HMGCR gene in myocardium was upregulated (P<0.05). Compared with the model group, the EF, FS and E/A was improved by andrographolide significantly (P<0.05), LVIDs was significantly decreased (P<0.01), the cardiomyocyte hypertrophy was alleviated, and the expression of HMGCR gene in myocardium was significantly downregulated (P<0.05).[Conclusion] Andrographolide can improve heart function of mice with heart failure induced by isoprenaline, and its mechanism may be related to the inhibition of HMG-CoA reductase and regulation of cholesterol synthesis. |
| Key words: Andrographolide heart failure network pharmacology mechanism |
