Clinical Trials for the Use of CoQ10 in Pre-eclampsia 辅酶Q10在先兆子痫患者中的应用试验

分类:医学文献 54 0

Pre-eclampsia (PE) is a complex pathology diagnosed during the second part of the pregnancy. The clinical features of PE are hypertension and proteinuria. This syndrome occurs in 3-8% of all pregnancies. The only cure for PE is delivery, and this syndrome is a leading cause of maternal and neonatal mortality and morbidity. The cause of PE is thought to originate from the placenta through the release of circulating factors that lead to a generalized systemic vascular endothelial dysfunction. The factors suspected include reactive oxygen species (ROS). It is strongly believed that ROS are major contributors of endothelial cell dysfunction leading to PE, since women affected by this syndrome show imbalanced ROS production, abnormal levels of antioxidant defenses, and increased blood and placental lipid peroxidation. Here, we discussed the rationale for the use of coenzyme Q10 (CoQ10), a vitamin-like antioxidant, during pregnancy to prevent PE.

先兆子痫发生在妊娠中期,是一种复杂疾病,其临床特征是高血压和蛋白尿,在孕妇中的病发率为3-8%。先兆子痫是造成孕产妇和新生儿死亡和发病的主要原因,唯一的治疗方法是分娩。先兆子痫被认为是由于胎盘通过释放循环因子导致全身性血管内皮功能障碍引起的,这些循环因子可能包括了活性氧。因为先兆子痫患者表现出活性氧生成失衡,抗氧化防御水平异常以及血液和胎盘胎质过氧化增加的症状,所以大家坚信活性氧是造成内皮细胞功能障碍的主要原因,并进一步导致先兆子痫。下面,我们讨论在孕期使用辅酶Q10(CoQ10,一种类似维生素的抗氧化物)来预防先兆子痫的基本原理。

The coenzyme Q10 is an essential component of the mitochondrial respiratory chain and a very efficient antioxidant under its reduced form, the ubiquinol-10. Indeed, ubiquinol-10 is more efficient than β–carotene, α-tocopherol, and lycopene in inhibiting low density oxidation in vivo (1). The CQ10 has also the ability to protect vitamin E from superoxide anion (O2-) attack (2). The oxidized (ubiquinone-10)/reduced (ubiquinol-10) ratio of CQ10 can be used as an oxidative stress marker in human plasma (3).

辅酶Q10是线粒体呼吸链的重要组成部分,辅酶Q10可还原为泛醇10,泛醇10是一种非常有效的抗氧化剂。实际上,泛醇10在抵制体内低密度氧化作用方面比β-胡萝上素,α-生育酚和番茄红素更有效(1)。辅酶Q10还具有保护维生素E免受超氧离子(O₂-)侵袭的功能(2)。辅酶Q10的氧化(泛醌10)和还原(泛醇10)比例可以用作人体血浆中的氧化应激标记物(3)。

In pre-eclampsia, the total CoQ10 level was shown to be decreased in serum and was associated with the severity of the syndrome (4). The total CoQ10 level was also reported to be decreased in pre-eclampsia plasma (5). However, CoQ10 level was shown to be increased in pre-eclampsia cord blood and placentas when compared to normotensive pregnancies. Interestingly, our group reported no increase of total CoQ10 level in plasma, but rather an increase in the ratio of oxidized to reduced form of CoQ10 in the blood of pre-eclampsia mothers (6). Also, our study showed that ubiquinol-10 was correlated with α-tocopherol in pre-eclampsia pregnancies only (6). The positive correlation between ubiquinol-10 and α-tocopherol could thus represent a coordinated defense mechanism against oxidative stress in pre-eclampsia.

在先兆子痫患者的血清中,辅酶Q10总量降低,降低程度与病症的严重程度相关(4)。有研究发现患者血浆中的辅酶Q10总量也有所降低(5)。不过,先兆子痫患者脐带血和胎盘中的辅酶Q10水平升高。有意思的是,我们研究小组发现先兆子痫母亲血液中血浆的辅酶Q10总量水平没有增加,但是辅酶Q10氧化型/还原型比值却增加了(6)。 另外,先兆子痫患者的泛醇10水平仅与α-生育酚水平正相关。这种相关性可能表示它们在抗氧化应激反应过程中具有协同防御机制。

Besides its efficient antioxidant properties, CoQ10 may have unsuspected roles on immune functions and the control of blood pressure in pre-eclampsia. Indeed, we discovered that plasmatic IL-18 level, a cytokine known to induce tumor necrosis factor-α (TNF-α), was positively correlated with the ubiquinol-10 in pre-eclampsia pregnancies only (7). Though, the exact impact of the latter on immune function remains to be determined. We also observed that CoQ10 (oxidized/reduced ratio) positively correlates with the prostacyclin (vasodilator) to thromboxane (vasoconstrictor) ratio (6). This ratio may partly explain the hypertension in pre-eclampsia. More work still need to be done to understand the impact of the redox state on immune and vasoactive mediators.

辅酶Q10不仅有高效的抗氧化特性,而且可能在增强先兆子痫患者的免疫功能和控制血压方面有潜在的未知作用。实际上,我们发现血浆IL-18水平(一种已知可诱导肿瘤坏死因子-α(TNF-α)的细胞因子)仅与先兆子痫妊娠患者的泛醇10水平正相关(7),虽然泛醇10对免疫功能的确切作用还未明确。我们还观察到辅酶Q10(氧化/还原比值)与前列环素(血管扩张剂)与血栓烷(血管收缩剂)的比值正相关(6)。这个比值可以部分解释先兆子痫的高血压现象,但仍需要进一步研究来了解氧化还原状态对免疫和血管活性介质的影响。

A recent study indicated that CoQ10 supplementation at a dose of 200 mg/day from 20 weeks of pregnancy until birth can prevent pre-eclampsia (8). In this randomized cohort, the placebo group was constituted of 74 women and the CoQ10 treated group of 80 women. The 25.6% incidence of pre-eclampsia in the placebo group was significantly reduced to 14.4% in the CoQ10-treated group. This encouraging study was performed in Quito, Ecuador at 2,800 m of altitude, a factor know to increase the incidence of pre-eclampsia.

最近一项研究表明,从怀孕20周起至分娩,每天补充200毫克辅酶Q10可以预防先兆子痫(8)。在这个随机队列研究中,受试对象包括74位服用安慰剂的女性和80位服用辅酶Q10的女性。研究结果令人激动,对照组先兆子痫的病发率为25.6%,而服用辅酶Q10的一组为14.4%。该研究是在厄瓜多尔基多2800米的海拔高度上进行的,高海拔也会增加先兆子痫的病发率。

References

参考文献

1. Stocker R, Bowry VW, Frei B (1991) Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does alpha-tocopherol. Proc Natl Acad Sci U S A 88:1646-1650

2. Stoyanovsky DA, Osipov AN, Quinn PJ, Kagan VE (1995) Ubiquinone-dependent recycling of vitamin E radicals by superoxide. Arch Biochem Biophys 323:343-351

3. Yamashita S, Yamamoto Y (1997) Simultaneous detection of ubiquinol and ubiquinone in human plasma as a marker of oxidative stress. Anal Biochem 250:66-73

4. Palan PR, Shaban DW, Martino T, Mikhail MS (2004) Lipid-soluble antioxidants and pregnancy: maternal serum levels of coenzyme Q10, alpha-tocopherol and gamma-tocopherol in preeclampsia and normal pregnancy. Gynecol Obstet Invest 58:8-13

5. Teran E, Racines-Orbe M, Vivero S, Escudero C, Molina G, Calle A (2003) Preeclampsia is associated with a decrease in plasma coenzyme Q10 levels. Free Radic Biol Med 35:1453-1456

6. Roland L, Gagne A, Belanger MC, Boutet M, Berthiaume L, Fraser WD, Julien P, Bilodeau JF (2010) Existence of compensatory defense mechanisms against oxidative stress and hypertension in preeclampsia. Hypertens Pregnancy 29:21-37

7. Roland L, Gagne A, Belanger MC, Boutet M, Julien P, Bilodeau JF (2010) Plasma interleukin-18 (IL-18) levels are correlated with antioxidant vitamin coenzyme Q(10) in preeclmpsia. Acta Obsete Gynecol Scand 89:360-366

8. Teran E, Hernandez I, Nieto B, Tavara R, Ocampo JE, Calle A (2009) Coenzyme Q10 supplementation during pregnancy reduces the risk of pre-eclampsia. Int J Gynaecol Obstet 105:43-45

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