Zhang Xinyu, Wang Lei, Guo Rong, Xiao Jie, Liu Xiaoling, Dong Mei, Luan Xiaorong, Ji Xiaoping, Lu Huixia
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Department of Cardiology, Ji'an Municipal Center People's Hospital, Ji'an, China.
Front Pharmacol. 2021 Oct 12;12:753881. doi: 10.3389/fphar.2021.753881. eCollection 2021.
Macrovascular complication of diabetes mellitus, characterized by increased aortic stiffness, is a major cause leading to many adverse clinical outcomes. It has been reported that ginsenoside Rb1 (Rb1) can improve glucose tolerance, enhance insulin activity, and restore the impaired endothelial functions in animal models. The aim of this study was to explore whether Rb1 could alleviate the pathophysiological process of arterial stiffening in diabetes and its potential mechanisms. Diabetes was induced in male C57BL/6 mice by administration of streptozotocin. These mice were randomly selected for treatment with Rb1 (10-60 mg/kg, i. p.) once daily for 8 weeks. Aortic stiffness was assessed using ultrasound and measurement of blood pressure and relaxant responses in the aortic rings. Mechanisms of Rb1 treatment were studied in MOVAS-1 VSMCs cultured in a high-glucose medium. Rb1 improved DM-induced arterial stiffening and the impaired aortic compliance and endothelium-dependent vasodilation. Rb1 ameliorated DM-induced aortic remodeling characterized by collagen deposition and elastic fibers disorder. MMP2, MMP9, and TGFβ1/Smad2/3 pathways were involved in this process. In addition, Rb1-mediated improvement of arterial stiffness was partly achieved via inhibiting oxidative stress in DM mice, involving regulating NADPH oxidase. Finally, Rb1 could blunt the inhibition effects of DM on AMPK phosphorylation. Rb1 may represent a novel prevention strategy to alleviate collagen deposition and degradation to prevent diabetic macroangiopathy and diabetes-related complications.
糖尿病的大血管并发症以主动脉僵硬度增加为特征，是导致许多不良临床结局的主要原因。据报道，人参皂苷Rb1（Rb1）可改善糖耐量、增强胰岛素活性，并在动物模型中恢复受损的内皮功能。本研究的目的是探讨Rb1是否能减轻糖尿病动脉僵硬化的病理生理过程及其潜在机制。通过给予链脲佐菌素诱导雄性C57BL/6小鼠患糖尿病。这些小鼠被随机选择接受Rb1（10 - 60mg/kg，腹腔注射）治疗，每日一次，共8周。使用超声以及测量主动脉环的血压和舒张反应来评估主动脉僵硬度。在高糖培养基中培养的MOVAS - 1血管平滑肌细胞中研究Rb1治疗的机制。Rb1改善了糖尿病诱导的动脉僵硬化以及受损的主动脉顺应性和内皮依赖性血管舒张。Rb1改善了以胶原沉积和弹性纤维紊乱为特征的糖尿病诱导的主动脉重塑。MMP2、MMP9和TGFβ1/Smad2/3信号通路参与了这一过程。此外，Rb1介导的动脉僵硬度改善部分是通过抑制糖尿病小鼠的氧化应激实现的，这涉及调节NADPH氧化酶。最后，Rb1可以减弱糖尿病对AMPK磷酸化的抑制作用。Rb1可能代表一种新的预防策略，以减轻胶原沉积和降解，预防糖尿病大血管病变和糖尿病相关并发症。
