Baker IDI Heart and Diabetes Institute, PO Box 6492, St Kilda Road Central, Melbourne, Victoria 8008, Australia.
Diabetologia. 2012 May;55(5):1544-53. doi: 10.1007/s00125-012-2495-3. Epub 2012 Feb 29.
AIMS/HYPOTHESIS: An increase in the production of reactive oxygen species is commonly thought to contribute to the development of diabetic cardiomyopathy. This study aimed to assess whether administration of the antioxidant coenzyme Q(10) would protect the diabetic heart against dysfunction and remodelling, using the db/db mouse model of type 2 diabetes. Furthermore, we aimed to compare the efficacy of coenzyme Q(10) to that of the ACE inhibitor ramipril.
Six-week-old non-diabetic db/+ mice and diabetic db/db mice received either normal drinking water or water supplemented with coenzyme Q(10) for 10 weeks. Endpoint cardiac function was assessed by echocardiography and catheterisation. Ventricular tissue was collected for histology, gene expression and protein analysis.
Untreated db/db diabetic mice exhibited hyperglycaemia, accompanied by diastolic dysfunction and adverse structural remodelling, including cardiomyocyte hypertrophy, myocardial fibrosis and increased apoptosis. Systemic lipid peroxidation and myocardial superoxide generation were also elevated in db/db mice. Coenzyme Q(10) and ramipril treatment reduced superoxide generation, ameliorated diastolic dysfunction and reduced cardiomyocyte hypertrophy and fibrosis in db/db mice. Phosphorylation of Akt, although depressed in untreated db/db mice, was restored with coenzyme Q(10) administration. We postulate that preservation of cardioprotective Akt signalling may be a mechanism by which coenzyme Q(10)-treated db/db mice are protected from pathological cardiac hypertrophy.
CONCLUSIONS/INTERPRETATION: These data demonstrate that coenzyme Q(10) attenuates oxidative stress and left ventricular diastolic dysfunction and remodelling in the diabetic heart. Addition of coenzyme Q(10) to the current therapy used in diabetic patients with diastolic dysfunction warrants further investigation.
目的/假设：活性氧的产生增加通常被认为有助于糖尿病心肌病的发展。本研究旨在评估抗氧化辅酶 Q(10)的给药是否会保护糖尿病心脏免受功能障碍和重塑，使用 2 型糖尿病 db/db 小鼠模型。此外，我们旨在比较辅酶 Q(10)与 ACE 抑制剂雷米普利的疗效。
6 周龄非糖尿病 db/+ 小鼠和糖尿病 db/db 小鼠接受正常饮用水或补充辅酶 Q(10)的水 10 周。通过超声心动图和导管插入术评估终点心功能。收集心室组织进行组织学、基因表达和蛋白质分析。
未经治疗的 db/db 糖尿病小鼠表现出高血糖，伴有舒张功能障碍和不良结构重塑，包括心肌细胞肥大、心肌纤维化和细胞凋亡增加。db/db 小鼠的全身脂质过氧化和心肌超氧化物生成也升高。辅酶 Q(10)和雷米普利治疗可降低超氧化物生成，改善舒张功能障碍，并减少 db/db 小鼠的心肌细胞肥大和纤维化。尽管未治疗的 db/db 小鼠中的 Akt 磷酸化受到抑制，但辅酶 Q(10)给药后恢复。我们推测，保护心脏保护 Akt 信号可能是辅酶 Q(10)治疗的 db/db 小鼠免受病理性心肌肥大的机制之一。
结论/解释：这些数据表明，辅酶 Q(10)可减轻糖尿病心脏中的氧化应激和左心室舒张功能障碍和重塑。在目前用于治疗舒张功能障碍的糖尿病患者中添加辅酶 Q(10)值得进一步研究。
