Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Department of Health Inspection and Quarantine, School of Public Health, Anhui Medical University, Hefei 230032, China.
Oxid Med Cell Longev. 2022 May 12;2022:6482363. doi: 10.1155/2022/6482363. eCollection 2022.
Endothelial dysfunction and cardiomyopathy are considered to be important vascular complications associated with diabetes. This study was designed to investigate whether capsaicin (CAP), a selective TRPV1 agonist, could prevent diabetes-induced endothelial dysfunction and cardiomyopathy.
Male Sprague Dawley rats aged 8 weeks were injected intraperitoneally with streptozotocin (STZ, 50 mg/kg) to establish the diabetes model. The diabetic rats were randomly divided into the untreated diabetes group (DM, 10/group) and diabetes plus CAP treatment group (DM+CAP, 10/group); meanwhile, the nondiabetic healthy rats were used as normal controls (10/group). DM+CAP group were treated with CAP by gavage for 8 weeks. The cultured mouse vascular endothelial cells were exposed to different concentrations of glucose in the presence or absence of CAP treatment. The TRPV1 inhibitor capsazepine (CPZ) and eNOS inhibitor L-NAME were used and experiment.
CAP treatment significantly decreased the serum total cholesterol (TC) and total triglyceride (TG) and ameliorated the pathogenesis and fibrosis in the heart, while did not significantly improve plasma glucose level and the body weights of diabetic rats. In addition, CAP enhanced the expression of TRPV1 and eNOS in the heart and normalized the vascular permeability under diabetic state. Similarly, CAP treatment also increased nitric oxide and reduced reactive oxygen species. The same results were observed in cultured mouse vascular endothelial cells by CAP treatment. These beneficial effects of CAP were abolished by either CPZ or L-NAME.
CAP might protect against hyperglycemia-induced endothelial dysfunction and diabetic cardiomyopathy through TRPV1/eNOS pathway.
内皮功能障碍和心肌病被认为是与糖尿病相关的重要血管并发症。本研究旨在探讨辣椒素(CAP),一种选择性 TRPV1 激动剂,是否可预防糖尿病引起的内皮功能障碍和心肌病。
8 周龄雄性 Sprague Dawley 大鼠经腹腔注射链脲佐菌素(STZ,50mg/kg)建立糖尿病模型。糖尿病大鼠随机分为未治疗糖尿病组(DM,10/组)和糖尿病加 CAP 治疗组(DM+CAP,10/组);同时,将非糖尿病健康大鼠作为正常对照组(10/组)。DM+CAP 组给予 CAP 灌胃 8 周。将培养的小鼠血管内皮细胞在存在或不存在 CAP 处理的情况下暴露于不同浓度的葡萄糖中。使用 TRPV1 抑制剂辣椒素(CPZ)和 eNOS 抑制剂 L-NAME 进行实验。
CAP 治疗可显著降低血清总胆固醇(TC)和总甘油三酯(TG),改善心脏的发病机制和纤维化,而对糖尿病大鼠的血糖水平和体重无显著改善。此外,CAP 增强了心脏中 TRPV1 和 eNOS 的表达,并在糖尿病状态下使血管通透性正常化。CAP 处理还增加了一氧化氮并减少了活性氧。在 CAP 处理的培养的小鼠血管内皮细胞中也观察到了相同的结果。这些 CAP 的有益作用被 CPZ 或 L-NAME 消除。
CAP 可能通过 TRPV1/eNOS 途径保护免受高血糖引起的内皮功能障碍和糖尿病心肌病。