Differential impact of atorvastatin vs pravastatin on progressive insulin resistance and left ventricular diastolic dysfunction in a rat model of type II diabetes
Differential impact of atorvastatin vs pravastatin on progressive insulin resistance and left ventricular diastolic dysfunction in a rat model of type II diabetes
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DOI：
10.1253/circj.71.144
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发表时间：
2007-01-01
影响因子：
3.3
通讯作者：
Kohno, Masakazu
中科院分区：
文献类型：
--
作者：
Chen, Yan;Ohmori, Koji;Kohno, Masakazu
背景他汀类药物对进行性胰岛素抵抗(IR)的影响及其后果一直存在争议，本研究采用自发性II型糖尿病(DM)大鼠模型，比较阿托伐他汀(AS)与普伐他汀(PS)的影响。方法与结果6周龄的大冢长埃文斯德岛肥胖大鼠从6周龄开始，每天给予AS或PS 100 mg/kg，共24周。AS的降脂效果明显好于PS。一系列口服葡萄糖耐量测试显示，仅PS可延缓新发糖尿病的发生。未治疗组大鼠血清脂联素进行性下降，瘦素和肿瘤坏死因子-α升高，血浆一氧化氮(NO)降低，PS较AS对此有更大的抑制作用。在30周时，PS，而不是AS，增加了白色脂肪组织中脂联素的表达。心肌内皮细胞一氧化氮合酶表达上调，转化生长因子-β1和单核细胞趋化蛋白-1mRNA的过度表达受PS的抑制作用大于AS。结论PS的适度降脂作用，而不是AS的强化降脂作用，可以预防新发的DM和舒张期功能障碍，这与较好的脂肪细胞因子水平和心脏氧化还原状态有关。
Background Controversy exists regarding the effects of statin therapy on progressive insulin resistance (IR) and its consequences, in the present study a rat model of spontaneously developing type II diabetes mellitus (DM) was used to examine the impact of atorvastatin (AS) vs pravastatin (PS).Methods and Results The Otsuka Long-Evans Tokushima Fatty rats were either untreated or treated with 100mg/kg per day of AS or PS from 6 weeks of age for 24 weeks. AS achieved much greater lipid lowering than PS. Serial oral glucose tolerance tests revealed new-onset diabetes was delayed by PS only. The untreated rats exhibited a progressive decrease in plasma adiponectin, increases in plasma leptin and tumor necrosis factor-a, and reduction of plasma nitric oxide (NO), which were limited more by PS than AS. PS, but not AS, enhanced adiponectin mRNA expression in white adipose tissue at 30 weeks. Cardiac endothelial NO synthase expression was upregulated, and overexpression of both transforming growth factor-beta 1 and monocyte chemoattractant protein-1 mRNA was limited more by PS than AS. Coronary perivascular fibrosis at 30 weeks was suppressed only by PS, which was accompanied by preserved left ventricular diastolic function assessed with Doppler echocardiography.Conclusions The moderate lipid lowering by PS, but not the intensive lipid lowering by AS, prevented new-onset DM and diastolic dysfunction in a rat model of IR, and this was associated with preferable adipocytokine profiles and cardiac redox states.