Department of Critical Care Medicine, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, 437199, China.
Department of Neonatology, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, 437199, China.
Cell Biochem Biophys. 2024 Sep;82(3):2427-2437. doi: 10.1007/s12013-024-01353-2. Epub 2024 Jun 15.
Diabetic cardiomyopathy (DCM) is a prevalent complication of diabetes mellitus characterized by cardiac dysfunction and myocardial remodeling. Farrerol (FA), an active ingredient in Rhododendron with various pharmacological activities, has an unclear specific role in DCM. Therefore, this study aims to investigate the effects of FA on DCM rats and elucidate its mechanism. The type 2 diabetes mellitus (T2DM) model was induced in adult male Sprague-Dawley rats by administering a high-fat diet for 8 weeks along with STZ injection. Subsequent to successful modeling, FA and the positive drug Dapagliflozin (Dapa) were orally administered via gavage for an additional 8-week period. After administration, the rats' body weight, fasting blood glucose, fasting insulin, and blood lipid profiles were quantified. Cardiac function was assessed through evaluation of cardiac function parameters, histopathological examination and measurement of myocardial enzyme markers were conducted to assess myocardial injury and fibrosis, Oil red O staining was utilized to evaluate myocardial lipid accumulation, wheat germ agglutinin (WGA) staining was used for assessing cardiomyocyte hypertrophy, and Western blot analysis was used to detect the proteins expression level of AMP-activated protein kinase (AMPK) pathway. The rat cardiomyocyte H9c2 were induced with palmitic acid to establish an in vitro cell model of myocardial lipid toxicity. Subsequently, the cells were subjected to treatment with FA and AMPK inhibitor Compound C, followed by assessment of lipid formation and expression levels of proteins related to the AMPK signaling pathway. The findings demonstrated that both FA and Dapa exhibited efficacy in ameliorating diabetic symptoms, cardiac dysfunction, myocardial fibrosis, cardiomyocyte hypertrophy, and lipid accumulation in T2DM rats. Additionally, they were found to enhance AMPK phosphorylation and PPARα expression while down-regulating CD36. Similarly, FA was observed to inhibit lipid formation in H9c2 and activate the AMPK signaling pathway. However, the improved effect of FA on lipotoxic cardiomyocytes induced by palmitic acid was partially reversed by Compound C. Therefore, the activation of the AMPK signaling pathway by FA may enhance cardiac lipid metabolism, thereby improving cardiac dysfunction and myocardial fibrosis in DCM rats.
糖尿病心肌病（DCM）是糖尿病的一种常见并发症，其特征为心脏功能障碍和心肌重构。法呢醇（FA）是一种具有多种药理活性的杜鹃花中的活性成分，其在 DCM 中的具体作用尚不清楚。因此，本研究旨在探讨 FA 对 DCM 大鼠的作用及其机制。通过给予高脂肪饮食 8 周并注射 STZ，诱导成年雄性 Sprague-Dawley 大鼠 2 型糖尿病（T2DM）模型。成功建模后，通过灌胃给予 FA 和阳性药物达格列净（Dapa），再进行 8 周的治疗。给药后，检测大鼠体重、空腹血糖、空腹胰岛素和血脂谱。通过评估心功能参数来评估心功能，进行组织病理学检查和心肌酶标志物测量来评估心肌损伤和纤维化，油红 O 染色评估心肌脂质堆积，小麦胚凝集素（WGA）染色评估心肌细胞肥大，Western blot 分析检测 AMP 激活蛋白激酶（AMPK）通路蛋白的表达水平。用棕榈酸诱导大鼠心肌细胞 H9c2 建立心肌脂质毒性的体外细胞模型。然后，用 FA 和 AMPK 抑制剂 Compound C 处理细胞，评估脂质形成和 AMPK 信号通路相关蛋白的表达水平。结果表明，FA 和 Dapa 均能改善 T2DM 大鼠的糖尿病症状、心功能障碍、心肌纤维化、心肌细胞肥大和脂质堆积。此外，它们还能增强 AMPK 磷酸化和 PPARα 表达，同时下调 CD36。同样，FA 能抑制 H9c2 中的脂质形成并激活 AMPK 信号通路。然而，Compound C 部分逆转了 FA 对棕榈酸诱导的脂毒性心肌细胞的改善作用。因此，FA 通过激活 AMPK 信号通路增强心脏脂质代谢，从而改善 DCM 大鼠的心功能障碍和心肌纤维化。
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