Wang Chih-Hsien, Chang Ru-Wen, Ko Ya-Hui, Tsai Pi-Ru, Wang Shoei-Shen, Chen Yih-Sharng, Ko Wen-Je, Chang Chun-Yi, Young Tai-Horng, Chang Kuo-Chu
Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan; Department of Surgery, National Taiwan University Hospital, Hsin-Chu Branch, Hsin-Chu, Taiwan; Department of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Department of Surgery and Traumatology, National Taiwan University Hospital, Taipei, Taiwan.
PLoS One. 2014 Mar 4;9(3):e90471. doi: 10.1371/journal.pone.0090471. eCollection 2014.
Without affecting the lipid profile, a low-dose treatment with atorvastatin contributes to the reduction of oxidative stress, inflammation, and adverse cardiovascular events in diabetes. In this study, we investigated whether low-dose atorvastatin exerts any beneficial effect on vascular dynamics in streptozotocin (STZ)-induced diabetes in male Wistar rats.
Diabetes was induced using a single tail-vein injection of STZ at 55 mg kg-1. The diabetic rats were treated daily with atorvastatin (10 mg kg-1 by oral gavage) for 6 weeks. They were also compared with untreated age-matched diabetic controls. Arterial wave reflection was derived using the impulse response function of the filtered aortic input impedance spectra. A thiobarbituric acid reactive substances measurement was used to estimate the malondialdehyde content.
The high plasma level of total cholesterol in the diabetic rats did not change in response to this low-dose treatment with atorvastatin. Atorvastatin resulted in a significant increase of 15.4% in wave transit time and a decrease of 33.5% in wave reflection factor, suggesting that atorvastatin may attenuate the diabetes-induced deterioration in systolic loads imposed on the heart. This was in parallel with its lowering of malondialdehyde content in plasma and aortic walls in diabetes. Atorvastatin therapy also prevented the diabetes-related cardiac hypertrophy, as evidenced by the diminished ratio of left ventricular weight to body weight.
These findings indicate that low-dose atorvastatin might protect diabetic vasculature against diabetes-associated deterioration in aorta stiffness and cardiac hypertrophy, possibly through its decrease of lipid oxidation-derived malondialdehyde.
在不影响血脂谱的情况下,低剂量阿托伐他汀治疗有助于降低糖尿病患者的氧化应激、炎症反应及不良心血管事件。在本研究中,我们调查了低剂量阿托伐他汀对链脲佐菌素(STZ)诱导的雄性Wistar大鼠糖尿病血管动力学是否具有有益作用。
通过单次尾静脉注射55 mg/kg的STZ诱导糖尿病。糖尿病大鼠每天经口灌胃给予阿托伐他汀(10 mg/kg),持续6周。同时将其与未治疗的年龄匹配的糖尿病对照组进行比较。利用滤波后的主动脉输入阻抗谱的脉冲响应函数推导动脉波反射。采用硫代巴比妥酸反应性物质测定法估算丙二醛含量。
糖尿病大鼠的高血浆总胆固醇水平在低剂量阿托伐他汀治疗后未发生变化。阿托伐他汀使波传播时间显著增加15.4%,波反射因子降低33.5%,这表明阿托伐他汀可能减轻糖尿病引起的心脏收缩期负荷恶化。这与其降低糖尿病大鼠血浆和主动脉壁中的丙二醛含量相一致。阿托伐他汀治疗还预防了糖尿病相关的心脏肥大,左心室重量与体重之比降低证明了这一点。
这些发现表明,低剂量阿托伐他汀可能通过降低脂质氧化衍生的丙二醛,保护糖尿病血管系统免受糖尿病相关的主动脉僵硬度恶化和心脏肥大的影响。