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α-硫辛酸对大鼠坐骨神经缺血再灌注损伤的保护作用

Protective Effect of Alpha Lipoic Acid on Rat Sciatic Nerve Ischemia Reperfusion Damage.

作者信息

Turamanlar Ozan, Özen Oğuz Aslan, Songur Ahmet, Yağmurca Murat, Akçer Sezer, Mollaoğlu Hakan, Aktaş Cevat

机构信息

Department of Anatomy, Afyon Kocatepe University Faculty of Medicine, Afyonkarahisar, Turkey.

Department of Anatomy, Namık Kemal University Faculty of Medicine, Tekirdağ, Turkey.

出版信息

Balkan Med J. 2015 Apr;32(2):196-202. doi: 10.5152/balkanmedj.2015.15619. Epub 2015 Apr 1.

Abstract

BACKGROUND

Alpha lipoic acid is a potent antioxidant that plays numerous roles in human health. This study examined the effect of ALA on rat sciatic nerve ischemia reperfusion damage.

AIMS

Protective effect of alpha lipoic acid (ALA) on sciatic nerve following ischemia-reperfusion in rats was investigated by using light microscopy and biochemical methods. Provided that the protective effect of ALA on sciatic nerve is proven, we think the damage to the sciatic nerve that has already occurred or might occur in patients for various reasons maybe prevented or stopped by giving ALA in convenient doses.

STUDY DESIGN

Animal experiment.

METHODS

Forty-two adult male Sprague-Dawley rats (250-300 grams) were used in this study. Rats were randomly divided into six groups including one control (Group 1), one sham (Group 2), two ischemia-reperfusion (Groups 3 and 4) and two treatment groups (Groups5 and 6). Doses of 60 and 100 mg/kg ALA were given (Group 5 and 6) intra peritoneally twice, 1 and 24 hours before the ischemia to each treatment group. Ischemia was carried out the abdominal aorta starting from the distal part of the renal vein for two hours followed by reperfusion for three hours. In immunohistochemical methods, fibronectin immunoreactivity was analyzed. For biochemical analyses, the tissues were taken in eppendorf microtubes and superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) enzyme activities as well as malondialdehyde (MDA) and nitricoxide (NO) levels were measured.

RESULTS

Fibronectin was observed to have increased significantly in the ischemia group; on the other hand, it was observed to have decreased in parallel to the doses in the ALA groups. Biochemical studies showed that SOD and GSHPx declined with ischemia-reperfusion, but the activities of these enzymes were increased in the treatment groups in parallel with the dose. It was found that increased MDA levels with ischemia-reperfusion were decreased in parallel with ALA dose. There were no statistically significant changes in NO.

CONCLUSION

Increased fibronectin observed after ischemia/reperfusion of rat sciatic nerve is reduced after the administration of ALA. This indicates that the function of fibronectin, to reconnect cut nerve segments and regenerate nerves, is more prominent than its function in tissue healing after ischemia. ALA administered before ischemia decreases MDA and increases SOD and GSHPx. We think that ALA may protect against the pathological changes in ischemic nerve and may be used to devise more efficient treatments.

摘要

背景

α-硫辛酸是一种强效抗氧化剂,在人体健康中发挥着多种作用。本研究考察了α-硫辛酸(ALA)对大鼠坐骨神经缺血再灌注损伤的影响。

目的

采用光学显微镜和生化方法研究α-硫辛酸(ALA)对大鼠坐骨神经缺血再灌注后的保护作用。如果ALA对坐骨神经的保护作用得到证实,我们认为对于因各种原因已经发生或可能发生坐骨神经损伤的患者,给予适当剂量的ALA可能预防或阻止这种损伤。

研究设计

动物实验。

方法

本研究使用了42只成年雄性Sprague-Dawley大鼠(体重250 - 300克)。大鼠被随机分为六组,包括一组对照组(第1组)、一组假手术组(第2组)、两组缺血再灌注组(第3组和第4组)以及两组治疗组(第5组和第6组)。对每个治疗组在缺血前1小时和24小时腹腔注射60毫克/千克和100毫克/千克的ALA两次。从肾静脉远端开始对腹主动脉进行两小时的缺血处理,随后进行三小时的再灌注。采用免疫组织化学方法分析纤连蛋白免疫反应性。进行生化分析时,将组织放入微量离心管中,测量超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSHPx)的酶活性以及丙二醛(MDA)和一氧化氮(NO)的水平。

结果

缺血组中观察到纤连蛋白显著增加;另一方面,在ALA组中纤连蛋白随着剂量增加而减少。生化研究表明,SOD和GSHPx在缺血再灌注时下降,但在治疗组中这些酶活性随着剂量增加而升高。发现缺血再灌注时升高的MDA水平随着ALA剂量增加而降低。NO没有统计学上的显著变化。

结论

大鼠坐骨神经缺血/再灌注后观察到的纤连蛋白增加在给予ALA后降低。这表明纤连蛋白在重新连接切断的神经段和神经再生方面的功能比其在缺血后组织愈合中的功能更突出。缺血前给予ALA可降低MDA并增加SOD和GSHPx。我们认为ALA可能预防缺血性神经的病理变化,并可用于设计更有效的治疗方法。

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