Zhu Meili, Hu Jiangbiao, Pan Yifan, Jiang Qian, Shu Chang
Department of Rehabilitation Medicine, the First People's Hospital of Yongkang, Yongkang, China.
Department of Cardiology, the First People's Hospital of Yongkang, Yongkang, China.
Cardiovasc Diagn Ther. 2024 Aug 31;14(4):576-588. doi: 10.21037/cdt-24-130. Epub 2024 Aug 14.
Heart failure (HF) remains one of the most common events in the progression of hypertension. Magnoflorine (MNF) has been shown beneficial effects on the cardiovascular system. However, the action of MNF on angiotensin (Ang) II-induced cardiac remodeling and its underlying mechanisms have not yet been characterised. Here, we assessed the action of MNF in the development of hypertension-related HF.
C57BL/6 male mice were subjected to Ang II through a micro-osmotic pump infusion continuously for 4 weeks to induce hypertensive HF. MNF (10 and 20 mg/kg) was administered in the final 2 weeks. Ang II content was measured by enzyme-linked immunosorbent assay (ELISA) kit. Values of ejection fraction (EF) and fractional shortening (FS) were detected using an ultrasound diagnostic instrument. The mRNA levels of hypertrophic and fibrotic genes were determined by real-time quantitative polymerase chain reaction (RT-qPCR). Haematoxylin and eosin (H&E), wheat germ agglutinin (WGA), Masson trichrome, and Sirius Red staining were used to analyse pathologic changes in heart tissues. The expression levels of phosphorylated AMP-activated protein kinase (AMPK), light chain 3 microtubule associated protein II (LC3 II) to LC3 I, and p62 were detected by western blot assay.
MNF significantly improved cardiac dysfunction and the content of creatine kinase-MB without altering blood pressure in Ang II-challenged mice. MNF obviously corrected the phenotypes of cardiac hypertrophy and fibrosis, including the high mRNA levels of atrial natriuretic peptide (), brain natriuretic peptide (), collagen1a (), transforming growth factor beta (), enlarged myocardial areas, and increased positive areas of Masson trichrome and Sirius Red staining. In addition, MNF alleviated oxidative injury, reflected by the upregulation of glutathione and the downregulation of reactive oxygen species and malondialdehyde. The activation of AMPK was elevated accompanied by an increased level of autophagy by MNF in hypertensive heart tissues. The therapeutic action of MNF was confirmed in Ang II-challenged H9c2 cells. Specifically, the AMPK inhibitor could eliminate the autophagy pathway in which MNF is involved.
MNF has benefits in hypertension-induced cardiac remodeling, which was partially associated with the improvement of oxidative stress via the mediation of the AMPK/autophagy axis.
心力衰竭（HF）仍然是高血压进展过程中最常见的事件之一。黄连碱（MNF）已被证明对心血管系统有有益作用。然而，MNF对血管紧张素（Ang）II诱导的心脏重塑的作用及其潜在机制尚未阐明。在此，我们评估了MNF在高血压相关HF发生发展中的作用。
将C57BL/6雄性小鼠通过微量渗透泵持续输注Ang II 4周以诱导高血压HF。在最后2周给予MNF（10和20 mg/kg）。采用酶联免疫吸附测定（ELISA）试剂盒测量Ang II含量。使用超声诊断仪检测射血分数（EF）和缩短分数（FS）值。通过实时定量聚合酶链反应（RT-qPCR）测定肥厚和纤维化基因的mRNA水平。采用苏木精-伊红（H&E）、麦胚凝集素（WGA）、Masson三色染色和天狼星红染色分析心脏组织的病理变化。通过蛋白质印迹法检测磷酸化的AMP激活蛋白激酶（AMPK）、轻链3微管相关蛋白II（LC3 II）与LC3 I的比值以及p62的表达水平。
MNF显著改善了Ang II攻击小鼠的心脏功能障碍和肌酸激酶-MB含量，而不改变血压。MNF明显纠正了心脏肥大和纤维化的表型，包括心房利钠肽（）、脑利钠肽（）、胶原1a（）、转化生长因子β（）的高mRNA水平、心肌面积增大以及Masson三色染色和天狼星红染色的阳性面积增加。此外，MNF减轻了氧化损伤，表现为谷胱甘肽上调以及活性氧和丙二醛下调。MNF使高血压心脏组织中AMPK的激活增加，同时自噬水平升高。MNF的治疗作用在Ang II攻击的H9c2细胞中得到证实。具体而言，AMPK抑制剂可消除MNF参与的自噬途径。
MNF对高血压诱导的心脏重塑有益，这部分与通过AMPK/自噬轴介导改善氧化应激有关。
