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胆碱补充可降低变应性气道疾病小鼠模型的氧化应激。

Choline supplementation reduces oxidative stress in mouse model of allergic airway disease.

机构信息

Allergy and Immunology Section, Institute of Genomics and Integrative Biology, Delhi 110007, India.

出版信息

Eur J Clin Invest. 2009 Oct;39(10):934-41. doi: 10.1111/j.1365-2362.2009.02190.x. Epub 2009 Jun 26.

Abstract

BACKGROUND

Asthma is a multi-factorial inflammatory disease associated with increased oxidative stress and altered antioxidant defences. We have evaluated the effect of choline on oxidative stress in a mouse model of airway disease.

MATERIALS AND METHODS

Balb/c mice were sensitised with 100 microg of ovalbumin on days 0 and 14, and challenged with aerosolized ovalbumin on days 25-27. Mice were administered 1 mg kg(-1) of choline via oral gavage or intranasal route on days 14-27. Mice were also administered 100 mg kg(-1) of alpha-lipoic acid as standard antioxidant. Total cell counts, eosinophils and eosinophil peroxidase (EPO) activity were determined in bronchoalveolar lavage (BAL) fluid. Reactive oxygen species (ROS), lipid peroxidation and isoprostanes levels were measured in BAL fluid. IL-13 and tumour necrosis factor-alpha (TNF-alpha) levels were also measured in BAL fluid and spleen cell culture supernatant. Nuclear factor kappaB (NFkappaB) p65 protein expression was measured after last ovalbumin challenge in nuclear and cytosolic extracts of lungs.

RESULTS

Compared with ovalbumin-challenged mice, choline and alpha-lipoic acid treated mice had significantly reduced eosinophilic infiltration and EPO activity in BAL fluid. Choline and alpha-lipoic acid treatment reduced ROS production and isoprostanes level significantly in BAL fluid and thus suppressed oxidative stress. Choline and alpha-lipoic acid administration by either route decreased lipid peroxidation levels and down regulated NFkappaB activity. Further, choline and/or alpha-lipoic acid treatment suppressed TNF-alpha level significantly as compared with that of ovalbumin-challenged mice.

CONCLUSIONS

Choline administration reduces oxidative stress possibly by modulating the redox status of the cell and inhibits inflammatory response in a mouse model.

摘要

背景

哮喘是一种多因素炎症性疾病,与氧化应激增加和抗氧化防御改变有关。我们评估了胆碱对气道疾病小鼠模型氧化应激的影响。

材料与方法

Balb/c 小鼠于第 0 天和第 14 天用 100μg 卵清蛋白致敏,并于第 25-27 天用雾化卵清蛋白激发。第 14-27 天,通过口服灌胃或鼻内途径给予小鼠 1mg/kg 的胆碱。还给予小鼠 100mg/kg 的α-硫辛酸作为标准抗氧化剂。在支气管肺泡灌洗液(BAL)中测定总细胞计数、嗜酸性粒细胞和嗜酸性过氧化物酶(EPO)活性。在 BAL 液中测定活性氧(ROS)、脂质过氧化和异前列腺素水平。还在 BAL 液和脾细胞培养上清液中测定白细胞介素 13(IL-13)和肿瘤坏死因子-α(TNF-α)水平。在最后一次卵清蛋白激发后,测量肺核和胞浆提取物中核因子 kappaB(NFkappaB)p65 蛋白的表达。

结果

与卵清蛋白激发的小鼠相比,胆碱和α-硫辛酸处理的小鼠 BAL 液中嗜酸性粒细胞浸润和 EPO 活性显著降低。胆碱和α-硫辛酸治疗显著降低了 BAL 液中 ROS 的产生和异前列腺素水平,从而抑制了氧化应激。两种途径给予胆碱和α-硫辛酸均可降低脂质过氧化水平并下调 NFkappaB 活性。此外,与卵清蛋白激发的小鼠相比,胆碱和/或α-硫辛酸治疗显著降低了 TNF-α 水平。

结论

胆碱给药通过调节细胞的氧化还原状态降低氧化应激,并抑制小鼠模型中的炎症反应。

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