Phytoestrogenic isoflavones daidzein and genistein reduce glucose-toxicity-induced cardiac contractile dysfunction in ventricular myocytes
Phytoestrogenic isoflavones daidzein and genistein reduce glucose-toxicity-induced cardiac contractile dysfunction in ventricular myocytes
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DOI：
10.1081/erc-120037730
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发表时间：
2004-01-01
影响因子：
2.1
通讯作者：
Ren, J
中科院分区：
文献类型：
--
作者：
Hintz, KK;Ren, J
流行病学证据表明，在饮食中摄入大量植物雌激素或植物雌激素的人群中，冠心病、癌症和骨质疏松症的发病率降低。谷物、蔬菜和药用植物中的植物雌激素的临床益处正引起公众越来越多的关注。在本研究中，我们研究了植物雌激素异黄酮大豆苷元和染料木黄酮对葡萄糖毒性诱导的模拟糖尿病心肌病的心脏机械功能障碍的影响。分离成年大鼠心室肌细胞，并在正常（NG，5.5mM）或高糖（HG，25.5MM）培养基中在不存在或存在大豆黄酮（50 μ M）或染料木黄酮（20 μ M）的情况下维持24小时。使用IonOptix（R）MyoCam系统评估心脏收缩指数，包括峰值缩短（PS）、最大缩短/再延长速度（+/- dL/dt）、达到PS的时间（TPS）和达到90%再延长的时间（TR 90）。与NG心肌细胞相比，维持在HG培养基中的心肌细胞显示出模拟体内糖尿病的机械功能改变，包括与正常TPS相关的PS、+/- dL/dt降低和TR 90延长。有趣的是，这些汞诱导的机械功能障碍被废除的大豆苷元或染料木素共孵育。然而，大豆苷元，而不是染料木素本身抑制NG心肌细胞PS。无论是大豆黄酮，也不影响染料木素在NG肌细胞测试的任何其他机械参数。总的来说，这些数据表明，植物雌激素类黄酮大豆苷元和染料木黄酮可以减少葡萄糖毒性诱导的心脏机械功能障碍，从而具有治疗糖尿病相关的心脏缺陷的潜力。
Epidemiological evidence suggests a reduction in the incidence of coronary heart disease, cancer and osteoporosis in populations with a high dietary intake of plant estrogen or phytoestrogen. The clinical benefit of phytoestrogens in cereals, vegetables and medicinal plants is attracting increasing attention for the general public. In the present study, we examined the effect of phytoestrogenic isoflavones daidzein and genistein on glucose toxicity-induced cardiac mechanical malfunction simulating diabetic cardiomyopathy. Adult rat ventricular myocytes were isolated and maintained for 24 hours in normal (NG, 5.5 mM) or high glucose (HG, 25.5 MM) medium in the absence or presence of isoflavones daidzein (50 muM) or genistein (20 muM). Cardiac contractile indices were evaluated using an IonOptix(R) MyoCam system including peak shortening (PS), maximal velocity of shortening/relengthening (+/- dL/dt), time-to-PS (TPS) and time-to-90% relengthening (TR90). Myocytes maintained in HG medium displayed altered mechanical function simulating in vivo diabetes including reduced PS, +/- dL/dt and prolonged TR90 associated with normal TPS compared to those from NG myocytes. Interestingly, these HG-induced mechanical dysfunctions were abolished by co-incubation of daidzein or genistein. However, daidzein but not genistein itself depressed PS in NG myocytes. Neither daidzein nor genistein affected any other mechanical parameters tested in NG myocytes. Collectively, these data suggest that the phytoestrogenic isoflavones daidzein and genistein may reduce glucose toxicity-induced cardiac mechanical dysfunction and thus possess therapeutic potential against diabetes-associated cardiac defects.