Chen Shu-Ming, Kuo Cheng-Deng, Ho Low-Tone, Liao Jyh-Fei
Department of Medical Research and Education, Nephrology Laboratory, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
Biol Trace Elem Res. 2007 Aug;118(2):111-9. doi: 10.1007/s12011-007-0005-0.
We previously reported that reduced platelet endogenous antioxidant enzymes activities are related to the low plasma zinc level in patients with end-stage renal failure (ESRF). In this study, we attempt to evaluate whether dietary zinc deprivation reduces the activities of endogenous antioxidant and then enhances oxidative stress in the unstimulated platelet of normal and 5/6 nephrectomized (Nx) rats because increased platelet oxidative stress is suggested to involve in the incidence of thrombotic and atherosclerotic diseases. Male Sprague-Dawley rats (n = 48) were fed a zinc-deficient diet and deionized distilled water for 1 week to induce reduction of plasma zinc level. Half of the rats continued on this diet for 4 weeks as zinc-deplete group, and the other half were maintained on the same diet but with zinc-supplemented water (120 mg/L zinc sulfate solution) to correct the reduction of plasma zinc level as zinc-replete group. Half of each group underwent 5/6 Nx, while the other half underwent sham operation. Another 12 normal rats were fed standard rat chow (containing 23.4% protein and 50 ppm zinc) and drank deionized distilled water as normal control rats. In zinc-deplete rats including sham-operated and 5/6 Nx rats exhibited lower endogenous antioxidant enzymes activities such as reduced glutathione (GSH), superoxide dismutase (SOD), and glutathione peroxidase (GPX) and higher malondialdehyde (MDA) levels than normal control rats in the unstimulated platelets. However, in zinc-replete rats including sham-operated and 5/6 Nx rats have a normal endogenous antioxidant enzymes activity and normal MDA levels in the unstimulated platelets. We suggest that in uremia, the low plasma zinc level may be a risk factor for thrombotic and atherosclerotic diseases because it reduces the activities of endogenous antioxidant enzymes and increases oxidative stress in the unstimulated platelet.
我们之前报道过，终末期肾衰竭（ESRF）患者血小板内源性抗氧化酶活性降低与血浆锌水平低有关。在本研究中，我们试图评估饮食中锌缺乏是否会降低内源性抗氧化剂的活性，进而增强正常大鼠和5/6肾切除（Nx）大鼠未受刺激血小板中的氧化应激，因为血小板氧化应激增加被认为与血栓形成和动脉粥样硬化疾病的发生有关。雄性Sprague-Dawley大鼠（n = 48）被喂食缺锌饮食和去离子蒸馏水1周，以诱导血浆锌水平降低。一半大鼠继续这种饮食4周作为缺锌组，另一半保持相同饮食，但饮用补充锌的水（120 mg/L硫酸锌溶液）以纠正血浆锌水平降低作为补锌组。每组的一半大鼠接受5/6 Nx手术，另一半接受假手术。另外12只正常大鼠喂食标准大鼠饲料（含23.4%蛋白质和50 ppm锌）并饮用去离子蒸馏水作为正常对照大鼠。在未受刺激的血小板中，包括假手术和5/6 Nx大鼠的缺锌大鼠，其谷胱甘肽（GSH）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPX）等内源性抗氧化酶活性较低，丙二醛（MDA）水平高于正常对照大鼠。然而，在包括假手术和5/6 Nx大鼠的补锌大鼠中，未受刺激血小板的内源性抗氧化酶活性和MDA水平正常。我们认为，在尿毒症中，低血浆锌水平可能是血栓形成和动脉粥样硬化疾病的危险因素，因为它会降低内源性抗氧化酶的活性并增加未受刺激血小板中的氧化应激。
