接上文 Part.3

 

Cardiovascular system disorders 心血管系统疾病

Little is known about the selective toxicity to the heart. Therefore, the following study demonstrated the relationship between the severity of copper deficiency-induced oxidative damage and the capacity of antioxidant defense in heart and liver to investigate a possible mechanism for the selective cardiotoxicity in rats. Copper deficiency induced a 2-fold increase in lipid peroxidation in the heart (thiobarbituric assay) but did not alter peroxidation in the liver. The antioxidant enzymatic activities of superoxide dismutase, catalase, and glutathione peroxidase were, respectively, 3-, 50- and 1.5-fold lower in the heart than in the liver, although these enzymatic activities were depressed in both organs by copper deficiency. In addition, the activity of glutathione reductase was 4 times lower in the heart than in the liver. The data suggest that a weak antioxidant defense system in the heart is responsible for the relatively high degree of oxidative damage in copper-deficient hearts [213].

对心脏的选择性毒性知之甚少。因此，以下研究证明了铜缺乏引起的氧化损伤的严重程度与心脏和肝脏的抗氧化防御能力之间的关系，以探讨大鼠选择性心脏毒性的可能机制。铜缺乏导致心脏中脂质过氧化增加2倍（硫代巴比妥试验），但不改变肝脏中的过氧化。心脏中的超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的抗氧化酶活性分别比肝脏低3倍、50倍和1.5倍，尽管这些酶活性在两个器官中都因铜缺乏而受到抑制。此外，心脏中谷胱甘肽还原酶的活性比肝脏中低4倍。数据表明，心脏中较弱的抗氧化防御系统是造成缺铜心脏相对高度氧化损伤的原因 [213]。

 

Several research groups have demonstrated that essential trace elements play important roles in states of cardiovascular diseases. The aim was to investigate whether there is a relationship between trace elements, Zn and Cu and the degree of atherosclerosis. The serum levels of zinc and copper were found to be significantly lower in patients with atherosclerosis than in the control group, but there were no significant differences in the serum levels of Cu and Zn between severe atherosclerosis and mild atherosclerosis. The present study revealed arelationship between the serum levels of zinc and copper and atherosclerosis, but not between these levels and the severity of the disease [214]. To understand the role of Cu and Zn in human blood both in controls as well as in cardiovascular (CVD) patients, whole blood samples of 181 CVD patients and 185 controls between the ages of 20-66 years were investigated. The mean blood-Cu levels (1.50 mg/l) were found as enhanced, whereas Zn levels (5.88 mg/l) were reduced in cardiovascular patients group. Cu/Zn ratios for CVD patients are also higher than in control subjects. However, when the CVD patients were checked for their systolic and diastolic pressure it was found that copper concentrations in these patients was significantly increased (p < 0.001) with the rise of blood systolic pressure, so a positive correlation was observed between copper and systolic pressure. Zn on the other hand has an inverse relation with systolic as well as diastolic pressure (p < 0.001). Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglyceride (TG) in blood samples have also been determined and their probable role in the CVD complication has been observed. A positive correlation of blood Cu with TC, TG, and LDL-C indicates that rise in blood Cu levels may initiate the development of CVD. An increase in Cu/Zn ratio can instigate the cardiovascular risk factor. The findings from this study can definitely update our knowledge of the role of Cu and Zn in the development of CVD risk in humans [215,216].

几个研究小组已经证明，必需微量元素在心血管疾病的状态中起着重要作用。这目的是调查trac之间是否存在关系元素、锌和铜以及动脉粥样硬化的程度。发现动脉粥样硬化患者的血清锌和铜水平显著低于对照组，但严重动脉粥样硬化和轻度动脉粥样硬化的血清铜和锌水平没有显著差异。本研究揭示了锌和铜的血清水平与动脉粥样硬化之间的关系，但这些水平与疾病的严重程度之间没有关系 [214]。为了了解铜和锌在对照和心血管 (CVD) 患者中的人体血液中的作用，研究了181名CVD患者和185名年龄在20-66岁之间的对照的全血样本。发现心血管患者组的平均血铜水平（1.50毫克/升）升高，而锌水平（5.88毫克/升）降低。心血管疾病患者的铜/锌比率也高于对照组。然而，当检查CVD患者的收缩压和舒张压时，发现这些患者的铜浓度随着血液收缩压的升高而显著增加（p<0.001），因此观察到铜与收缩压之间呈正相关.另一方面，锌与收缩压和舒张压成反比关系（p<0.001）。还测定了血液样本中的总胆固醇 （TC）、低密度脂蛋白胆固醇 （LDL-C）、高密度脂蛋白胆固醇和甘油三酯 （TG），并观察了它们在CVD并发症中的可能作用。血铜与TC、TG和LDL-C呈正相关，表明血铜水平升高可能引发CVD。铜/锌比率的增加会引发心血管危险因素。这项研究的结果绝对可以更新我们对铜和锌在人类CVD风险发展中的作用的认识 [215,216]。

 

Cu and Zn Interactions with Medications 铜和锌与药物的相互作用

 

Zn/Antibiotcs 锌/抗生素

Both quinolone antibiotics and tetracycline antibiotics interact with zinc in the gastrointestinal tract, inhibiting the absorption of both zinc and the antibiotic. Taking the antibiotic at least 2 hours before or 4–6 hours after taking a zinc supplement minimizes this interaction [217,218].

喹诺酮类抗生素和四环素类抗生素都与胃肠道中的锌相互作用，抑制锌和抗生素的吸收。服用锌补充剂前至2小时或服用锌补充剂后4-6小时服用抗生素可最大限度地减少这种相互作用 [217,218]。

 

Zn/Penicilamine 锌/青霉胺

Zinc can reduce the absorption and action of penicillamine. To minimize this interaction, individuals should take zinc supplements at least 2 hours before or after taking penicillamine [86].

锌能降低青霉胺的吸收和作用。为了尽量减少这种相互作用，个人应在服用青霉胺之前或之后至少2小时服用锌补充剂 [86]。

 

Zn/Diuretics 锌/利尿剂

Thiazide diuretics such as chlorthalidone and hydrochlorothiazide increase urinary zinc excretion by as much as 60 %. Prolonged use of thiazide diuretics could deplete zinc tissue levels, so clinicians should monitor zinc status in patients taking these medications [219].

噻嗪类利尿剂，如氯噻酮和氢氯噻嗪，可使尿中锌的排泄量增加60%。长期使用噻嗪类利尿剂可能会消耗锌组织水平，因此临床医生应监测服用这些药物的患者的锌状态 [219]。

 

Cu/Nonsteroidal anti-inflammatory drugs [NSAIDs] 铜/非甾体抗炎药 [NSAIDs]

Copper binds to NSAIDs and appears to enhance their antiinflammatory activity [220].

铜与非甾体抗炎药结合，似乎增强了它们的抗炎活性 [220]。

 

Cu/Penicilamine 铜/青霉胺

Penicillamine reduces copper levels that may be the intended use - as a helating agent in the case of Wilson's disease to reduce toxic copperdeposits [153].

青霉胺降低了可能是预期用途的铜水平-在Wilson’s 病的情况下作为一种促进剂以减少有毒的铜沉积物 [153]。

 

Cu/Antacids 铜/抗酸剂

Antacids may reduce copper absorption by decreasing the amount of hydrochloric acid in the stomach [221].

抗酸剂可通过减少胃中盐酸的量来减少铜的吸收 [221]。

 

Cu/Allopurinol 铜/别嘌醇

The studies suggest that allopurinol may reduce copper levels [222].

研究表明，别嘌醇可能会降低铜水平 [222]。

 

Cu/Oral contraceptives 铜/口服避孕药

Oral contraceptives increase the absorption of copper. Estrogen replacement for post-menopausal women can increase blood levels of copper. Estrogen enhances the absorption and half-life of copper which in turn inhibits the absorption of zinc [223].

口服避孕药增加铜的吸收。绝经后妇女的雌激素替代品可以增加血液中的铜水平。雌激素增强铜的吸收和半衰期，进而抑制锌的吸收[223]。

 

Superoxide Dismutase/Valproic acid 超氧化物歧化酶/丙戊酸

The recent study evaluated changes in antioxidant status in blood during valproate monotherapy of adult patients with epilepsy. Significant differences between the study group and controls were found. The activity of erythrocyte SOD was higher in patients treated with valproate for a longer period (7-14 years) in comparison to controls (p=0.001) and patients with a short period of VPA treatment (p<0.001). Patients with uncontrolled epilepsy exhibited higher serum Zn than seizure-free patients (p=0.041). The antioxidant status of epileptic patients was modified by valproate monotherapy. The frequency of seizures and duration of VPA therapy were associated with changes of oxidative/antioxidative balance [224].

最近的研究评估了成年癫痫患者丙戊酸盐单药治疗期间血液中抗氧化状态的变化。发现研究组和对照组之间存在显著差异。与对照组 (p=0.001) 和短期VPA治疗的患者 (p<0.001) 相比，用丙戊酸盐治疗较长时间 (7-14年) 的患者的红细胞SOD活性更高。癫痫未控制患者的血清锌含量高于无癫痫患者 (p=0.041)。癫痫患者的抗氧化状态通过丙戊酸盐单药治疗得到改善。癫痫发作的频率和VPA治疗的持续时间与氧化/抗氧化平衡的变化有关 [224]。

 

Conclusion/Summary 结论/总结

The human body has an elaborate system for managing and regulating the amount of key trace metals circulating in blood and stored in cells. When this system fails to function properly, abnormal levels and ratios of trace metals can develop. One of the most common trace-metal imbalances is elevated copper and depressed zinc. The ratio of copper to zinc is clinically more important than the concentration of either of these trace metals. Zn is the second most abundant transition metal in organisms after iron and it is the only metal which appears in all enzyme classes, while copper is present in every tissue of the body, but is stored primarily in the liver, with fewer amounts found in the brain, heart, kidney, and muscles. Zinc is involved in numerous aspects of cellular metabolism. It is required for the catalytic activity of more than 200 enzymes and it plays a role in immune function, wound healing, protein synthesis, DNA synthesis and cell division. Zinc possesses antioxidant properties, which may protect against accelerated aging and helps speed up the healing process after an injury. Copper plays an important role in our metabolism, largely because it allows many critical enzymes to function properly. Copper is essential for maintaining the strength of the skin, blood vessels, epithelial and connective tissue throughout the body. Cu plays a role in the production of hemoglobin, myelin, melanin and it also keeps thyroid gland functioning normally. Copper can act as both an antioxidant and a pro-oxidant. As an antioxidant, Cu scavenges or neutralize free radicals and may reduce or help prevent some of the damage they cause. When copper acts as a pro-oxidant at times, it promotes free radical damage. More than the concentration of Zn or Cu in blood serum, it is important the balance between them. If the balance is changed several organic systems can be affected. Different diseases can be prevented when supplements are taken, and different drugs affect Cu and Zn concentrations what can cause the onset of different diseases.

人体有一套精细的系统来管理和调节血液中循环和储存在细胞中的关键微量金属的数量。当该系统无法正常运行时，微量金属的水平和比例可能会出现异常。最常见的微量金属失衡之一是铜含量升高和锌含量降低。铜与锌的比例在临床上比这些微量金属的浓度更重要。锌是生物体中仅次于铁的第二丰富的过渡金属，它是唯一出现在所有酶类中的金属，而铜存在于身体的每个组织中，但主要储存在肝脏中，在肝脏中的含量较少大脑、心脏、肾脏和肌肉。锌参与细胞代谢的许多方面。它是200多种酶的催化活性所必需的，它在免疫功能、伤口愈合、蛋白质合成、DNA合成和细胞分裂中发挥作用。锌具有抗氧化特性，可以防止加速老化，并有助于加速受伤后的愈合过程。铜在我们的新陈代谢中发挥着重要作用，主要是因为它允许许多关键酶正常发挥作用。铜对于维持全身皮肤、血管、上皮和结缔组织的强度至关重要。铜在血红蛋白、髓磷脂、黑色素的产生中发挥作用，它还能保持甲状腺正常运作。铜可以作为抗氧化剂和促氧化剂。作为一种抗氧化剂，铜可以清除或中和自由基，并可能减少或帮助防止它们造成的一些损害。当铜有时充当促氧化剂时，它会促进自由基损伤。比血清中锌或铜的浓度更重要的是它们之间的平衡。如果平衡发生变化，几个有机系统可能会受到影响。服用补充剂可以预防不同的疾病，不同的药物会影响铜和锌的浓度，从而导致不同的疾病发作。

 

References 参考文献

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