Wang Yitong, An Xiangbo, Wang Feng, Jiang Yinong
Department of Cardiology, First Affiliated Hospital of Dalian Medical University, Dalian, China.
Department of Interventional Therapy, First Affiliated Hospital of Dalian Medical University, Dalian, China.
Biomed Pharmacother. 2024 Mar;172:116253. doi: 10.1016/j.biopha.2024.116253. Epub 2024 Feb 15.
Ventricular remodeling refers to the structural and functional changes of the heart under various stimuli or disease influences and may also be accompanied by myocardial fibrosis, where an excessive amount of fibrous tissue appears in the myocardial tissue, affecting the heart's normal contraction and relaxation. Hypertension is posing the potential risk of causing myocardial injury and remodeling. The significance of the renin-angiotensin-aldosterone system (RAAS) in myocardial remodeling cannot be overlooked. Drug targeting of RAAS can effectively lower blood pressure and reduce left ventricular mass. Studies have shown that ginsenoside Rh4 can inhibit oxidative stress and inflammatory responses. In this study, a myocardial remodeling model was established using angiotensin (Ang) II, and the inhibitory effect of RH4 on myocardial hypertrophy and remodeling induced by Ang II was investigated using pathological staining and quantitative polymerase chain reaction (qPCR). Immunofluorescence and qPCR demonstrated that Rh4 causes myocardial hypertrophy and the generation of reactive oxygen species (ROS) in vitro. The Rh4 target was identified using transcriptomics. The findings indicated that RH4 could inhibit myocardial hypertrophy, inflammatory fibrosis, and oxidative stress induced by Ang II, suggesting potential cardiovascular protection effects. In vitro experiments have shown that Rh4 inhibits myocardial hypertrophy. Transcriptomics revealed that nuclear factor interleukin-3 (NFIL3) is a downstream regulator of Rh4. By constructing AAV9-NFIL3 and injecting it into mice, it was found that NFIL3 overexpression interfered with anti-Ang II-induced myocardial remodeling of Rh4. These results indicate that Rh4 demonstrates potential therapeutic effects on myocardial hypertrophy and fibrosis.
心室重构是指心脏在各种刺激或疾病影响下发生的结构和功能变化，还可能伴有心肌纤维化，即心肌组织中出现过量纤维组织，影响心脏正常的收缩和舒张。高血压正构成导致心肌损伤和重构的潜在风险。肾素-血管紧张素-醛固酮系统（RAAS）在心肌重构中的意义不可忽视。针对RAAS的药物可有效降低血压并减少左心室质量。研究表明，人参皂苷Rh4可抑制氧化应激和炎症反应。在本研究中，使用血管紧张素（Ang）II建立心肌重构模型，并通过病理染色和定量聚合酶链反应（qPCR）研究Rh4对Ang II诱导的心肌肥大和重构的抑制作用。免疫荧光和qPCR表明，Rh4在体外可导致心肌肥大和活性氧（ROS）生成。利用转录组学鉴定了Rh4的靶点。研究结果表明，Rh4可抑制Ang II诱导的心肌肥大、炎症性纤维化和氧化应激，提示其具有潜在的心血管保护作用。体外实验表明，Rh4可抑制心肌肥大。转录组学显示，核因子白细胞介素-3（NFIL3）是Rh4的下游调节因子。通过构建AAV9-NFIL3并将其注射到小鼠体内，发现NFIL3过表达会干扰Rh4对Ang II诱导的心肌重构的抑制作用。这些结果表明，Rh4对心肌肥大和纤维化具有潜在治疗作用。
