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AS-IV 通过改善 2 型糖尿病大鼠模型的心肌脂质代谢对糖尿病心肌病的保护作用。

Protective effects of AS-IV on diabetic cardiomyopathy by improving myocardial lipid metabolism in rat models of T2DM.

机构信息

Key Laboratory of Anti-Inflammatory and Immunopharmacology, Ministry of Education, Department of Pharmacology, Basic Medicine College, Anhui Medical University. Hefei, 230032, Anhui, China.

Key Laboratory of Anti-Inflammatory and Immunopharmacology, Ministry of Education, Department of Pharmacology, Basic Medicine College, Anhui Medical University. Hefei, 230032, Anhui, China.

出版信息

Biomed Pharmacother. 2020 Jul;127:110081. doi: 10.1016/j.biopha.2020.110081. Epub 2020 Mar 31.

Abstract

Diabetic cardiomyopathy (DCM) is one of the main complications of type 2 diabetes mellitus (T2DM), and it is also one of the main causes of heart failure and death in advanced diabetes. The myocardial lipotoxic injury induced by abnormal lipid metabolism plays an important role in the occurrence and development of DCM, such as myocardial inflammation and fibrosis, ultimately leading to myocardial remodeling and cardiac insufficiency. Astragaloside IV (AS-IV) has many pharmacological effects such as anti-oxidation, anti-inflammatory, immune regulation, and anti-ischemic brain damage. This study was performed to investigate whether AS-IV could prevent T2DM-induced cardiomyopathy and regulate the abnormal myocardial lipid metabolism in diabetes. In this study, the T2DM model was induced by feeding with high-fat food and injected with low-dose STZ in rats. Then the model rats were treated with AS-IV and metformin (Met) for 8 weeks. The results showed that AS-IV improved cardiac systolic and diastolic function, and ameliorated the cardiac histopathological changes in the T2DM rats. Moreover, AS-IV significantly improved circulating TC, TG and HDL levels and cardiac lipid accumulation in T2DM rats as well as in high-fat diet (HFD) rats. Furthermore, AS-IV significantly inhibited the expressions of TNF-α, IL-6 and IL-1β and myocardial fibrosis in T2DM rats, which might be attributed to the improvement of myocardial lipid metabolism, ultimately improving cardiac function in T2DM rats. Taken together, these data suggested that AS-IV has protective effects on T2DM-induced myocardial injury in rats, and its mechanism may be related to the improvement of lipid metabolism in cardiomyocytes.

摘要

糖尿病心肌病(DCM)是 2 型糖尿病(T2DM)的主要并发症之一,也是晚期糖尿病心力衰竭和死亡的主要原因之一。异常脂质代谢引起的心肌脂毒性损伤在 DCM 的发生和发展中起重要作用,如心肌炎症和纤维化,最终导致心肌重构和心功能不全。黄芪甲苷(AS-IV)具有抗氧化、抗炎、免疫调节和抗缺血性脑损伤等多种药理作用。本研究旨在探讨 AS-IV 是否可以预防 T2DM 诱导的心肌病,并调节糖尿病异常心肌脂质代谢。在这项研究中,通过高脂饮食喂养和小剂量 STZ 注射诱导大鼠 T2DM 模型。然后,用 AS-IV 和二甲双胍(Met)治疗模型大鼠 8 周。结果表明,AS-IV 改善了 T2DM 大鼠的心脏收缩和舒张功能,并改善了糖尿病大鼠的心脏组织病理学变化。此外,AS-IV 显著改善了 T2DM 大鼠和高脂饮食(HFD)大鼠的循环 TC、TG 和 HDL 水平以及心脏脂质堆积。此外,AS-IV 显著抑制了 T2DM 大鼠 TNF-α、IL-6 和 IL-1β 的表达和心肌纤维化,这可能归因于心肌脂质代谢的改善,最终改善了 T2DM 大鼠的心脏功能。综上所述,这些数据表明 AS-IV 对大鼠 T2DM 诱导的心肌损伤具有保护作用,其机制可能与改善心肌细胞脂质代谢有关。

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