Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Jinzhou Medical University, Jinzhou, Liaoning, China (mainland).
Department of Internal Medicine-Cardiovascular, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China (mainland).
Med Sci Monit. 2019 Feb 15;25:1232-1241. doi: 10.12659/MSM.913244.
BACKGROUND Simvastatin, an HMG-CoA reductase inhibitor, has been reported to exert multiple protective effects on the cardiovascular system. However, the molecular mechanism remains to be examined. The present study was designed to study the effects of simvastatin on cardiac hypertrophy in diabetic rats and to explore its potential mechanism. MATERIAL AND METHODS Sprague-Dawley rats were assigned into a control (Con) group, a streptozotocin (STZ) group, and a STZ+simvastatin (STZ+SIM) group. The level of reactive oxygen species (ROS) was measured by using dihydroethidium (DHE) staining. The protein expressions of p65, IκBα, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), calpain-1, and endothelial nitric oxide synthase (eNOS) were examined by Western blot analysis. qPCR was used to detect the levels of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP). RESULTS Simvastatin improved the cardiac hypertrophy of diabetic rats, as demonstrated by decreases in the ratios of left ventricular weight/body weight (LVW/BW) and heart weight/body weight (HW/BW) and by the downregulation of mRNA expression of BNP and ANP in the heart tissue. Simvastatin decreased the protein expressions of VCAM-1, ICAM-1, IL-6, and TNF-α, increased eNOS protein expression, and limited an increase in ROS levels in the heart tissue. Simvastatin increased IkBa protein expression in cytoplasm and inhibited the translocation of p65, the subunit of nuclear factor-κB (NF-κB) to the nucleus from the cytoplasm of the heart tissue. Furthermore, simvastatin attenuated the activity of calpain and calpain-1 protein expression in heart tissue. CONCLUSIONS Simvastatin attenuates cardiac hypertrophy in diabetic rats, which might be due to the attenuation of oxidative stress and inflammation induced by calpain-1-mediated activation of NF-κB.
羟甲基戊二酰辅酶 A 还原酶抑制剂辛伐他汀已被报道对心血管系统具有多种保护作用。然而，其分子机制仍需进一步研究。本研究旨在探讨辛伐他汀对糖尿病大鼠心肌肥厚的影响及其潜在机制。
将 Sprague-Dawley 大鼠分为对照组（Con）、链脲佐菌素（STZ）组和 STZ+辛伐他汀（STZ+SIM）组。使用二氢乙啶（DHE）染色测定活性氧（ROS）水平。采用 Western blot 分析检测 p65、IκBα、血管细胞黏附分子-1（VCAM-1）、细胞间黏附分子-1（ICAM-1）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、钙蛋白酶-1 和内皮型一氧化氮合酶（eNOS）的蛋白表达。qPCR 用于检测脑钠肽（BNP）和心钠肽（ANP）的水平。
辛伐他汀改善了糖尿病大鼠的心肌肥厚，表现为左心室重量/体重（LVW/BW）和心脏重量/体重（HW/BW）比值降低，心脏组织中 BNP 和 ANP 的 mRNA 表达下调。辛伐他汀降低了 VCAM-1、ICAM-1、IL-6 和 TNF-α 的蛋白表达，增加了 eNOS 蛋白表达，并限制了心脏组织中 ROS 水平的升高。辛伐他汀增加了细胞质中 IkBa 蛋白的表达，并抑制了核因子-κB（NF-κB）亚基 p65从细胞质向细胞核的转位。此外，辛伐他汀减弱了心脏组织中钙蛋白酶和钙蛋白酶-1 蛋白的活性。
辛伐他汀减轻糖尿病大鼠的心肌肥厚，这可能是由于钙蛋白酶-1 介导的 NF-κB 激活导致的氧化应激和炎症反应减弱所致。
