Department of Endocrinology, Diabetes and Metabolism, Graduate School of Medicine, Nippon Medical School.
Food and Health Science Research Unit, Graduate School of Agricultural Science, Tohoku University.
J Atheroscler Thromb. 2019 Dec 1;26(12):1075-1083. doi: 10.5551/jat.48223. Epub 2019 Apr 11.
Although metformin treatment has been reported to reduce the risk of cardiovascular events in patients with type 2 diabetes, the underlying mechanisms have not been elucidated fully. Here we assessed atherosclerotic lesion formation in newly established 2 mouse lines with different blood glucose levels (Oikawa-Nagao Diabetes-Prone [ON-DP] and -Resistant [ON-DR]) to evaluate the effect of metformin on early-stage atherosclerosis.
Mildly hyperglycemic ON-DP and normoglycemic ON-DR female mice fed an atherogenic diet for 20 weeks (8-28 weeks of age). During the feeding period, one group of each mouse line received metformin in drinking water (0.1%), while another group received water alone as control. Atherosclerotic lesion formation in the aortic sinus was quantitively analyzed from the oil red O-stained area of the serial sections.
Metformin treatment did not affect food intake, body weight, and casual blood glucose levels within each mouse line during the 20-week feeding period. Nevertheless, metformin treatment significantly reduced atherosclerotic lesion formation in the ON-DP mice (59% of control), whereas no significant effect of metformin was observed in the lesion size of the ON-DR mice.
Metformin can attenuate early-stage atherogenesis in mildly hyperglycemic ON-DP mice. Pleiotropic effects of metformin, beyond its glucose-lowering action, may contribute to the antiatherogenic property in the early-stage atherosclerosis.
尽管已有报道称二甲双胍治疗可降低 2 型糖尿病患者发生心血管事件的风险，但其中的具体机制尚未完全阐明。本研究通过评估两种不同血糖水平（Oikawa-Nagao 糖尿病易感型[ON-DP]和耐异型[ON-DR]）新建立的小鼠模型中动脉粥样硬化病变的形成，来评估二甲双胍对早期动脉粥样硬化的影响。
对喂食致动脉粥样硬化饮食（8-28 周龄）的轻度高血糖 ON-DP 和正常血糖 ON-DR 雌性小鼠进行研究。在喂食期间，每组小鼠分别给予二甲双胍饮水（0.1%）或单独给予水作为对照。采用油红 O 染色连续切片的方法定量分析主动脉窦处动脉粥样硬化病变的形成。
在 20 周的喂食期间，二甲双胍处理并未影响各小鼠模型的饮食摄入、体重和随机血糖水平。然而，二甲双胍处理可显著减少 ON-DP 小鼠的动脉粥样硬化病变形成（对照组的 59%），而对 ON-DR 小鼠的病变大小无明显影响。
二甲双胍可减轻轻度高血糖 ON-DP 小鼠的早期动脉粥样硬化形成。除了降低血糖作用之外，二甲双胍的多效性作用可能有助于其发挥早期抗动脉粥样硬化特性。
