Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
Oxid Med Cell Longev. 2017;2017:1092015. doi: 10.1155/2017/1092015. Epub 2017 Sep 12.
Simvastatin is a lipid-lowering agent used to treat hypercholesterolemia and to reduce the risk of heart disease. This study scrutinized the beneficial effects of simvastatin on experimental diabetic cardiomyopathy (DCM), pointing to the role of hyperglycemia-induced oxidative stress and inflammation. Diabetes was induced by intraperitoneal injection of streptozotocin and both control and diabetic rats received simvastatin for 90 days. Diabetic rats showed significant cardiac hypertrophy, body weight loss, hyperglycemia, and hyperlipidemia. Serum creatine kinase MB (CK-MB) and troponin I showed a significant increase in diabetic rats. Simvastatin significantly improved body weight, attenuated hyperglycemia and hyperlipidemia, and ameliorated CK-MB and troponin I. Simvastatin prevented histological alterations and deposition of collagen in the heart of diabetic animals. Lipid peroxidation and nitric oxide were increased in the heart of diabetic rats whereas antioxidant defenses were decreased. These alterations were significantly reversed by simvastatin. In addition, simvastatin decreased serum inflammatory mediators and expression of NF-B in the diabetic heart. Cardiac caspase-3 was increased in the diabetic heart and decreased following treatment with simvastatin. In conclusion, our results suggest that simvastatin alleviates DCM by attenuating hyperglycemia/hyperlipidemia-induced oxidative stress, inflammation, and apoptosis.
辛伐他汀是一种降脂药物，用于治疗高胆固醇血症和降低心脏病风险。本研究探讨了辛伐他汀对实验性糖尿病心肌病（DCM）的有益作用，指出了高血糖诱导的氧化应激和炎症的作用。糖尿病通过腹腔注射链脲佐菌素诱导，对照组和糖尿病大鼠均接受辛伐他汀治疗 90 天。糖尿病大鼠表现出明显的心脏肥大、体重减轻、高血糖和高血脂。糖尿病大鼠的血清肌酸激酶 MB（CK-MB）和肌钙蛋白 I 显著增加。辛伐他汀显著改善了体重，减轻了高血糖和高血脂，并改善了 CK-MB 和肌钙蛋白 I。辛伐他汀预防了糖尿病动物心脏的组织学改变和胶原沉积。糖尿病大鼠心脏中的脂质过氧化和一氧化氮增加，而抗氧化防御减少。这些改变被辛伐他汀显著逆转。此外，辛伐他汀降低了糖尿病心脏中的血清炎症介质和 NF-B 的表达。糖尿病心脏中的半胱氨酸天冬氨酸蛋白酶-3（caspase-3）增加，用辛伐他汀治疗后减少。总之，我们的结果表明，辛伐他汀通过减轻高血糖/高血脂诱导的氧化应激、炎症和细胞凋亡来缓解 DCM。
