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用胆碱酯酶抑制剂联合抗氧化剂治疗阿尔茨海默病。

Treatment of Alzheimer's disease with a cholinesterase inhibitor combined with antioxidants.

机构信息

Loyola University Chicago School of Medicine, Maywood, IL, USA.

出版信息

Neurodegener Dis. 2010;7(1-3):193-202. doi: 10.1159/000295663. Epub 2010 Mar 12.

DOI:10.1159/000295663
PMID:20224285
Abstract

A formula (formula F) was prepared to counteract oxidative stress (OS) in the brain. The formula contained the most common antioxidants and was intended to: (a) protect proteins, lipids, DNA and proteoglycans from oxidation (carnosine, coenzyme Q(10), vitamin E, vitamin C, beta-carotene, selenium, L-cysteine and ginkgo biloba); (b) reduce homocysteine (HCy) blood levels (vitamins B(6), B(9) and B(12)), and (c) sustain the pentose phosphate cycle in circulating cells (vitamins B(1), B(2) and B(3)). Formula F contained low doses of each antioxidant component and was administered in a two-phase ampoule. A cohort of 52 patients (21 males and 31 females) affected with moderate probable AD (according to NINCDS-ARDA and NINCS-AIREN criteria) already being treated with donepezil (5 mg/day for at least two months) was randomly divided into two groups, and followed for 6 months. A double-blind design was used in which 26 cases were treated once a day with formula F plus donepezil, and the other 26 with placebo plus donepezil. The level of OS was measured on the basis of a d-ROMs test (which measures plasma hydroperoxides), plasma HCy and glutathione, and percentage of sickle erythrocytes. The two patient groups were comparable for all variables (age, sex, concomitant diseases, ApoE epsilon4, MMSE II score, OS, antioxidant reserve and sickle erythrocytes). Forty-eight subjects completed the trial. Significant decreases in OS and HCy were only observed when there was an increase in glutathione (in erythrocytes) and a decrease in sickle erythrocytes in patients treated with formula F. The MMSE II score remained almost the same in the group treated with donepezil and placebo, whereas some significant improvements were found in the group treated with donepezil plus formula F.

摘要

一种用于对抗大脑氧化应激(OS)的配方(配方 F)被制备出来。该配方包含最常见的抗氧化剂,旨在:(a)保护蛋白质、脂质、DNA 和蛋白聚糖免受氧化(肌肽、辅酶 Q(10)、维生素 E、维生素 C、β-胡萝卜素、硒、L-半胱氨酸和银杏叶);(b)降低血液中同型半胱氨酸(HCy)水平(维生素 B(6)、B(9)和 B(12)),和(c)维持循环细胞中的戊糖磷酸循环(维生素 B(1)、B(2)和 B(3))。配方 F 含有每种抗氧化剂成分的低剂量,并以两阶段安瓿形式给药。一组 52 名(21 名男性和 31 名女性)患有中度可能的 AD(根据 NINCDS-ARDA 和 NINCS-AIREN 标准)的患者已经接受了多奈哌齐(每天 5 毫克,至少两个月)治疗,随机分为两组,并随访 6 个月。使用双盲设计,其中 26 例每天一次接受配方 F 加多奈哌齐治疗,另 26 例接受安慰剂加多奈哌齐治疗。OS 水平根据 d-ROMs 测试(测量血浆过氧化物)、血浆 HCy 和谷胱甘肽以及镰状红细胞的百分比来测量。两组患者在所有变量(年龄、性别、伴随疾病、ApoE epsilon4、MMSE II 评分、OS、抗氧化储备和镰状红细胞)方面均具有可比性。48 名受试者完成了试验。只有当接受配方 F 治疗的患者的谷胱甘肽(红细胞)增加和镰状红细胞减少时,OS 和 HCy 才会显著降低。接受多奈哌齐和安慰剂治疗的组的 MMSE II 评分几乎保持不变,而接受多奈哌齐加配方 F 治疗的组则发现了一些显著的改善。

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