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肉碱酯可预防大鼠海马体短暂性前脑缺血后的氧化应激损伤和能量消耗。

Carnitine esters prevent oxidative stress damage and energy depletion following transient forebrain ischaemia in the rat hippocampus.

作者信息

Al-Majed Abdulhakeem A, Sayed-Ahmed Mohamed M, Al-Omar Fadhal A, Al-Yahya Abdulaziz A, Aleisa Abdulaziz M, Al-Shabanah Othman A

机构信息

Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

出版信息

Clin Exp Pharmacol Physiol. 2006 Aug;33(8):725-33. doi: 10.1111/j.1440-1681.2006.04425.x.

Abstract
  1. The present study investigated whether propionyl-L-carnitine (PLC) has neuroprotective effects, similar to those reported for acetyl-L-carnitine (AC), against transient forebrain ischaemia-induced neuronal damage and biochemical derangement in the rat hippocampal CA1 region. 2. In total, 105 adult male Wistar albino rats were divided into seven groups of 15 animals each. The first three groups were injected i.p. with normal saline, AC (300 mg/kg) or PLC (300 mg/kg) for 7 successive days. The next three groups were injected i.p. with the same doses of normal saline, AC or PLC immediately after the induction of 10 min forebrain ischaemia and i.p. injections were continued for 7 successive days. Rats in the seventh group were subjected to sham-operated ischaemia and injected with normal saline for 7 successive days. 3. Seven days after treatment, animals were killed and their brains isolated for histopathological examination and biochemical studies. 4. Forebrain ischaemia resulted in a significant decrease in the number of intact neurons (77%), ATP concentration (51%) and glutathione content (32%), whereas there was a significant increase in the production of thiobarbituric acid-reactive substances (TBARS; 71%) and total nitrate/nitrite (NOx; 260%) in hippocampal tissues. 5. Administration of either AC or PLC attenuated forebrain ischaemia-induced neuronal damage, manifested by a greater number of intact neurons, ATP and glutathione, as well as a decrease in TBARS and NOx in hippocampal tissues. 6. Results from the present study suggest, for the first time, that PLC attenuates forebrain ischaemia-induced neuronal injury, oxidative stress and energy depletion in the hippocampal CA1 region. Propionyl-L-carnitine has neuroprotective effects similar to AC and could have a potential use in the treatment of neurodegenerative diseases. 7. The results of the present study will open up new perspectives for the use of PLC in the treatment of neurodegenerative diseases associated with, or secondary to, myocardial ischaemia-reperfusion injury and chronic circulatory failure.
摘要
  1. 本研究调查了丙酰-L-肉碱(PLC)是否具有与乙酰-L-肉碱(AC)报道的类似的神经保护作用,以对抗短暂性前脑缺血诱导的大鼠海马CA1区神经元损伤和生化紊乱。2. 总共105只成年雄性Wistar白化大鼠被分为七组,每组15只动物。前三组连续7天腹腔注射生理盐水、AC(300mg/kg)或PLC(300mg/kg)。接下来的三组在诱导10分钟前脑缺血后立即腹腔注射相同剂量的生理盐水、AC或PLC,并连续7天进行腹腔注射。第七组大鼠接受假手术缺血,并连续7天注射生理盐水。3. 治疗7天后,处死动物并分离其大脑用于组织病理学检查和生化研究。4. 前脑缺血导致完整神经元数量显著减少(77%)、ATP浓度显著降低(51%)和谷胱甘肽含量显著降低(32%),而海马组织中硫代巴比妥酸反应性物质(TBARS;71%)和总硝酸盐/亚硝酸盐(NOx;260%)的产生显著增加。5. AC或PLC的给药减轻了前脑缺血诱导的神经元损伤,表现为海马组织中完整神经元、ATP和谷胱甘肽数量增加,以及TBARS和NOx减少。6. 本研究结果首次表明,PLC减轻了前脑缺血诱导的海马CA1区神经元损伤、氧化应激和能量耗竭。丙酰-L-肉碱具有与AC相似的神经保护作用,可能在神经退行性疾病治疗中有潜在用途。7. 本研究结果将为PLC在治疗与心肌缺血再灌注损伤和慢性循环衰竭相关或继发的神经退行性疾病中开辟新的前景。

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