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硫辛酸通过调节氧化还原紊乱,降低糖尿病大鼠抗氧化酶和热休克蛋白的 O-GlcNAc 修饰,从而保持红细胞的结构和功能完整性。

Alpha-lipoic acid preserves the structural and functional integrity of red blood cells by adjusting the redox disturbance and decreasing O-GlcNAc modifications of antioxidant enzymes and heat shock proteins in diabetic rats.

机构信息

Institute for Biological Research Siniša Stanković, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.

出版信息

Eur J Nutr. 2012 Dec;51(8):975-86. doi: 10.1007/s00394-011-0275-3. Epub 2011 Nov 18.

DOI:10.1007/s00394-011-0275-3
PMID:22094580
Abstract

PURPOSE

The aim of this study was to investigate whether the daily administration of α-lipoic acid (LA) during 4 weeks prevents the redox disturbance in red blood cells (RBC) described in diabetes

METHODS

Multiple low-dose streptozotocin (STZ) diabetes was induced in rats by the administration of 40 mg/kg STZ intraperitoneally (i.p.) for 5 consecutive days. LA was applied at a dose of 10 mg/kg i.p. for 4 weeks, starting from the last day of STZ administration.

RESULTS

The LA-treated diabetic rats exhibited a general systemic improvement, revealed as the near restoration of body weight and of essential biochemical parameters. The latter was displayed as decreased hyperglycemia, lower triglyceride levels and lower serum activities of alanine aminotransferases and aspartate aminotransferases that point to a general improvement of diabetes-linked organ "lesions". The LA-treated diabetic rats also exhibited significant alleviation of oxidative stress, manifested as decreased lipid peroxidation and lower glycation levels of serum proteins and hemoglobin, while the RBC exhibited increased activities of antioxidant enzymes and elevated levels of reduced glutathione. In RBC, this was accompanied by decreased post-translational glycosylation by O-bound β-N-acetylglucosamine (O-GlcNAc) of the antioxidant enzymes superoxide dismutase and catalase and of heat shock proteins HSP70 and HSP90.

CONCLUSION

LA through its powerful antioxidant activity preserves the structural and functional integrity of RBC in diabetes. The RBC can then assume a more efficient role as the first line of systemic defense against diabetic complications arising from oxidative stress-induced damage of other tissues and organs.

摘要

目的

本研究旨在探讨连续 4 周每天给予α-硫辛酸(LA)是否可以预防糖尿病中描述的红细胞(RBC)氧化还原紊乱。

方法

通过腹腔内(i.p.)给予 40 mg/kg STZ 连续 5 天,在大鼠中诱导多次低剂量链脲佐菌素(STZ)糖尿病。LA 以 10 mg/kg i.p.的剂量应用 4 周,从 STZ 给药的最后一天开始。

结果

用 LA 治疗的糖尿病大鼠表现出全身状况的普遍改善,表现为体重和基本生化参数的几乎恢复。后者表现为高血糖降低、甘油三酯水平降低、丙氨酸氨基转移酶和天冬氨酸氨基转移酶血清活性降低,这表明与糖尿病相关的器官“损伤”得到了普遍改善。用 LA 治疗的糖尿病大鼠还表现出氧化应激的显著缓解,表现为脂质过氧化降低和血清蛋白和血红蛋白的糖化水平降低,而 RBC 表现出抗氧化酶活性增加和还原型谷胱甘肽水平升高。在 RBC 中,这伴随着抗氧化酶超氧化物歧化酶和过氧化氢酶以及热休克蛋白 HSP70 和 HSP90 的 O 结合β-N-乙酰葡萄糖胺(O-GlcNAc)的翻译后糖基化减少。

结论

LA 通过其强大的抗氧化活性在糖尿病中保持 RBC 的结构和功能完整性。然后,RBC 可以作为全身防御系统的第一道防线,发挥更有效的作用,抵抗由其他组织和器官氧化应激诱导的损伤引起的糖尿病并发症。

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