Chess David J, Xu Wenhong, Khairallah Ramzi, O'Shea Karen M, Kop Willem J, Azimzadeh Agnes M, Stanley William C
Department of Physiology, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.
Am J Physiol Heart Circ Physiol. 2008 Dec;295(6):H2223-30. doi: 10.1152/ajpheart.00563.2008. Epub 2008 Oct 17.
We have previously shown that high-sugar diets increase mortality and left ventricular (LV) dysfunction during pressure overload. The mechanisms behind these diet-induced alterations are unclear but may involve increased oxidative stress in the myocardium. The present study examined whether high-fructose feeding increased myocardial oxidative damage and exacerbated systolic dysfunction after transverse aortic constriction (TAC) and if this effect could be attenuated by treatment with the antioxidant tempol. Immediately after surgery, TAC and sham mice were assigned to a high-starch diet (58% of total energy intake as cornstarch and 10% fat) or high-fructose diet (61% fructose and 10% fat) with or without the addition of tempol [0.1% (wt/wt) in the chow] and maintained on the treatment for 8 wk. In response to TAC, fructose-fed mice had greater cardiac hypertrophy (55.1% increase in the heart weight-to-tibia length ratio) than starch-fed mice (22.3% increase in the heart weight-to-tibia length ratio). Treatment with tempol significantly attenuated cardiac hypertrophy in fructose-fed TAC mice (18.3% increase in the heart weight-to-tibia ratio). Similarly, fructose-fed TAC mice had a decreased LV area of fractional shortening (from 38+/-2% in sham to 22+/-4% in TAC), which was prevented by tempol treatment (33+/-3%). Markers of lipid peroxidation in fructose-fed TAC hearts were also blunted by tempol. In conclusion, tempol significantly blunted markers of cardiac hypertrophy, LV remodeling, contractile dysfunction, and oxidative stress in fructose-fed TAC mice.
我们之前已经表明,高糖饮食会增加压力超负荷期间的死亡率和左心室(LV)功能障碍。这些饮食诱导的改变背后的机制尚不清楚,但可能涉及心肌氧化应激增加。本研究探讨了高果糖喂养是否会增加横向主动脉缩窄(TAC)后心肌氧化损伤并加重收缩功能障碍,以及这种效应是否可以通过抗氧化剂tempol治疗来减轻。手术后立即将TAC和假手术小鼠分配到高淀粉饮食(总能量摄入的58%为玉米淀粉,10%为脂肪)或高果糖饮食(61%果糖和10%脂肪),添加或不添加tempol[饲料中0.1%(重量/重量)],并维持治疗8周。对TAC的反应中,果糖喂养的小鼠比淀粉喂养的小鼠有更大的心脏肥大(心脏重量与胫骨长度比值增加55.1%)(心脏重量与胫骨长度比值增加22.3%)。tempol治疗显著减轻了果糖喂养的TAC小鼠的心脏肥大(心脏重量与胫骨比值增加18.3%)。同样,果糖喂养的TAC小鼠左心室缩短分数面积降低(从假手术组的38±2%降至TAC组的22±4%),而tempol治疗可预防这种情况(33±3%)。tempol也使果糖喂养的TAC心脏中的脂质过氧化标志物减弱。总之,tempol显著减弱了果糖喂养的TAC小鼠的心脏肥大、左心室重塑、收缩功能障碍和氧化应激标志物。