阿托伐他汀抑制健康 Sprague-Dawley 大鼠主动脉中晚期糖基化终产物诱导的 RAGE 表达。
Atorvastatin inhibits the expression of RAGE induced by advanced glycation end products on aortas in healthy Sprague-Dawley rats.
机构信息
Department of Endocriology and Metabolic Disease, East Hospital, Tongji University School of Medicine, Shanghai, 200120 China.
Department of Endocriology, Shanghai Ninth People's Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai, 200120 China.
出版信息
Diabetol Metab Syndr. 2014 Sep 23;6(1):102. doi: 10.1186/1758-5996-6-102. eCollection 2014.
BACKGROUND
Atorvastatin can downregulate the expression of receptor for advanced glycation end products (RAGE) in the aortas of diabetic rats. However, its effect on healthy rats remains unclear. The aim of this study was to observe the direct impact of atorvastatin on advanced glycation end products- (AGEs) induced RAGE expression in healthy Sprague Dawley (SD) rats.
METHODS
SD rats received AGE-BSA (20 mg/kg/day or 40 mg/kg/day), dual treatment (AGE-BSA 40 mg/kg/day and atorvastatin 20 mg/kg/day) or no treatment for 12 and 24 weeks, respectively. The deposition of AGEs and expression of RAGE in the animals' aortas were assessed by Quantitative RT-PCR, immunohistochemistry, and western-blot tests. Serum levels of AGEs were measured using ELISA.
RESULTS
AGE-BSA upregulated the serum level of AGEs, deposition of AGEs, and expression of RAGE in aortas in a time- and dose-dependent way that can accelerate the development and progression of atherosclerosis. These upregulations could be significantly attenuated by atorvastatin in the absence of its lipid-lowering effects. These data provide further evidence for the novo mechanism of atorvastatin's pleiotropic effect.
CONCLUSION
Atorvastatin has a direct inhibitory effect on AGEs-RAGE expression in healthy SD rats. These potential pleiotropic vasculoprotective effects are independent of effects on glucose and lipid control.
背景
阿托伐他汀可以下调糖尿病大鼠主动脉中晚期糖基化终产物（RAGE）的表达。然而，其对健康大鼠的影响尚不清楚。本研究旨在观察阿托伐他汀对健康 Sprague Dawley（SD）大鼠中晚期糖基化终产物（AGEs）诱导的 RAGE 表达的直接影响。
方法
SD 大鼠分别接受 AGE-BSA（20mg/kg/天或 40mg/kg/天）、双重治疗（AGE-BSA 40mg/kg/天和阿托伐他汀 20mg/kg/天）或不治疗 12 周和 24 周。通过定量 RT-PCR、免疫组织化学和 Western blot 试验评估动物主动脉中 AGEs 的沉积和 RAGE 的表达。使用 ELISA 测量血清 AGEs 水平。
结果
AGE-BSA 以时间和剂量依赖的方式上调血清 AGEs 水平、AGEs 沉积和主动脉 RAGE 表达，加速动脉粥样硬化的发生和发展。阿托伐他汀在不降低血脂的情况下，可显著减轻这些上调。这些数据为阿托伐他汀多效作用的新机制提供了进一步证据。
结论
阿托伐他汀对健康 SD 大鼠的 AGEs-RAGE 表达具有直接抑制作用。这些潜在的多效性血管保护作用独立于对葡萄糖和脂质控制的影响。
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