Control of plasma glucose with alpha-glucosidase inhibitor attenuates oxidative stress and slows the progression of heart failure in mice
Control of plasma glucose with alpha-glucosidase inhibitor attenuates oxidative stress and slows the progression of heart failure in mice
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DOI：
10.1016/j.cardiores.2006.01.021
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发表时间：
2006-04-01
影响因子：
10.8
通讯作者：
Kitakaze, M
中科院分区：
文献类型：
--
作者：
Liao, YL;Takashima, S;Kitakaze, M
目的：有研究表明，降低血糖水平有助于延长啮齿动物的寿命，同时限制食物摄入，高血糖已被证实是心血管疾病（CVD）的危险因素，提高了更好的血糖控制可能减缓CVD进展的可能性。本研究旨在确定是否糖耐量受损的发展过程中的心脏肥大和心力衰竭，以及是否严格的血糖控制可以降低heartfault.Methods的严重程度：在雄性C57 BL/6小鼠，横向主动脉缩窄（TAC），创建心脏肥大和心力衰竭。结果：TAC小鼠随机喂养后血糖浓度较高，伏格列波糖（一种α-糖苷酶抑制剂）可使其血糖浓度降至100 mg/dL左右。TAC后4周，伏格列波糖组的心脏重量/体重比和肺重量/体重比均低于TAC组。超声心动图和侵入性血流动力学检查显示伏格列波糖治疗小鼠的左心室功能改善。伏格列波糖治疗降低了NADPH氧化酶亚单位（p47（phox））的心肌表达。葡萄糖剂量依赖性地增加新生大鼠心肌细胞蛋白质的合成和p47（phox）蛋白的表达，而夹竹桃苷（NADPH氧化酶抑制剂）阻止蛋白质合成的增强由高glucose.Conclusion：通过伏格列波糖治疗改善血糖控制抑制心脏重构，降低心肌氧化应激在心脏压力超负荷小鼠。(c)2006年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
Objective: It has been suggested that reduction in glucose levels contributes to the prolongation of life span of rodents in conjunction with restricted food intake, and hyperglycemia has been confirmed as a risk factor for cardiovascular disease (CVD), raising the possibility that better glycemic control could slow the progression of CVD. This study was designed to determine whether impaired glucose tolerance develops during the progression of cardiac hypertrophy and heart failure, and whether tight glycemic control could reduce the severity of heart failure.Methods: In male C57BL/6 mice, transverse aortic constriction (TAC) was employed to create cardiac hypertrophy and heart failure. The involvement of NADPH in TAC mice and cardiac myocytes in the neonatal rat was investigated.Results: The random-fed plasma glucose concentration was higher in TAC mice, and it was reduced to about 100 mg/dL by voglibose (an alpha-glycosidase inhibitor). Four weeks after TAC, both the heart weight/body weight ratio and the lung weight/body weight ratio were lower in the voglibose group than in the TAC group. Echocardiographic and invasive hemodynamic examination showed improvement of left ventricular function in voglibose-treated mice. Voglibose treatment decreased the myocardial expression of an NADPH oxidase subunit (p47(phox)). Glucose dose-dependently increased both neonatal rat myocyte protein synthesis and the expression of p47(phox) protein, while apocynin (an NADPH oxidase inhibitor) blocked the enhancement of protein synthesis by high glucose.Conclusion: Improvement of glycemic control through voglibose therapy inhibited cardiac remodeling by decreasing myocardial oxidative stress in mice with cardiac pressure overload. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.