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抗坏血酸、α-生育酚和别嘌呤醇对兔骨骼肌缺血再灌注损伤的影响:一项实验研究。

Effects of ascorbic Acid, alpha-tocopherol and allopurinol on ischemia-reperfusion injury in rabbit skeletal muscle: an experimental study.

作者信息

Erkut Bilgehan, Özyazıcıoğlu Ahmet, Karapolat Bekir Sami, Koçoğulları Cevdet Uğur, Keles Sait, Ateş Azman, Gundogdu Cemal, Kocak Hikmet

机构信息

Department of Cardiovascular Surgery, Atatürk University Medical Faculty, Erzurum, Turkey.

出版信息

Drug Target Insights. 2007;2:249-58. Epub 2007 Nov 21.

Abstract

PURPOSE

Ischemia reperfusion injury to skeletal muscle, following an acute arterial occlusion is important cause of morbidity and mortality. The aim of the present study was to determine and evaluate the effects of ascorbic acide, alpha-tocopherol and allopurinol on ischemia reperfusion injury in rabbit skeletal muscle.

METHODS

Forty-eight New Zealand white rabbits, all male, weighing between 2.5 to 3.0 (mean 2.8) kg, were used in the study. They were separated into four groups. Group I was the control group without any drugs. The other groups were treatment groups (groups II, III, and IV). Group II rabbits administrated 50 mg/kg ascorbic acide and 100 mg/kg alpha-tocopherol 3 days prior to ischemia, group III rabbits received 50 mg/kg allopurinol 2 days prior to ischemia, and group IV rabbits were administrated both 50 mg/kg ascorbic acide, 100 mg/kg alpha-tocopherol 3 days prior to ischemia and 50 mg/kg allopurinol 2 days prior to ischemia. Two hours ischemia and 2 hours reperfusion were underwent to the treatment groups. At the end of the reperfusion periods, muscle samples were taken from rectus femoris muscle for determination of superoxide dismutase, catalase and glutathione peroxidase activities as antioxidant enzymes, and malondialdehyde as an indicator of lipid peroxidation and xanthine oxidase levels as source hydroxyl radical. Besides, histopathological changes (edema, inflammation, ring formation and splitting formation) were evaluated in the muscle specimens.

RESULTS

In the treatment groups; superoxide dismutase (U/mgprotein), catalase (U/mgprotein), and glutathione peroxidase (U/mgprotein) levels increased, malondialdehyde (nmol/mgprotein) and xanthine oksidase (mU/mgprotein) levels decreased compared to control I ( p < 0.05). Increase of superoxide dismutase, catalase, and glutathione peroxidase levels were the highest and decrease of malondialdehyde and xanthine oxidase levels were the highest in group IV compared to groups II and III, but no significant as statistically. Also amount of cellular injury in group II, III, and IV were lower than group I.

CONCLUSIONS

Antioxidant medication may help lowering ischemia reperfusion injury. In our study, all drug medications are shown to be able to have an effective role for preventing ischemia reperfusion injury. Moreover, ascorbic acide + alpha-tocopherol + allopurinol group (group IV) may have a beneficial effect to decrease the local and systemic damage due to ischemia-reperfusion injury.

摘要

目的

急性动脉闭塞后骨骼肌的缺血再灌注损伤是发病和死亡的重要原因。本研究的目的是确定并评估抗坏血酸、α-生育酚和别嘌呤醇对兔骨骼肌缺血再灌注损伤的影响。

方法

本研究使用了48只雄性新西兰白兔,体重在2.5至3.0(平均2.8)千克之间。它们被分为四组。第一组为未使用任何药物的对照组。其他组为治疗组(第二、三、四组)。第二组兔子在缺血前3天给予50毫克/千克抗坏血酸和100毫克/千克α-生育酚,第三组兔子在缺血前2天给予50毫克/千克别嘌呤醇,第四组兔子在缺血前3天给予50毫克/千克抗坏血酸、100毫克/千克α-生育酚,在缺血前2天给予50毫克/千克别嘌呤醇。对治疗组进行2小时缺血和2小时再灌注。在再灌注期结束时,从股直肌采集肌肉样本,用于测定超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶作为抗氧化酶的活性,以及丙二醛作为脂质过氧化的指标和黄嘌呤氧化酶水平作为羟基自由基的来源。此外,对肌肉标本进行组织病理学变化(水肿、炎症、环状形成和分裂形成)评估。

结果

在治疗组中;与对照组I相比,超氧化物歧化酶(单位/毫克蛋白质)、过氧化氢酶(单位/毫克蛋白质)和谷胱甘肽过氧化物酶(单位/毫克蛋白质)水平升高,丙二醛(纳摩尔/毫克蛋白质)和黄嘌呤氧化酶(毫单位/毫克蛋白质)水平降低(p < 0.05)。与第二组和第三组相比,第四组中超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶水平的升高最高,丙二醛和黄嘌呤氧化酶水平的降低最高,但无统计学显著差异。第二、三、四组的细胞损伤量也低于第一组。

结论

抗氧化药物可能有助于降低缺血再灌注损伤。在我们的研究中,所有药物均显示对预防缺血再灌注损伤有有效作用。此外,抗坏血酸+α-生育酚+别嘌呤醇组(第四组)可能对减少缺血再灌注损伤引起的局部和全身损伤有有益作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/97c5/3155224/0567d1a185a5/dti-2-2007-249f1.jpg

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