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前列腺素E1、褪黑素和土霉素对脊髓损伤动物模型中脂质过氧化、抗氧化防御系统、对氧磷酶(PON1)活性及同型半胱氨酸水平的影响

Effects of prostaglandin E1, melatonin, and oxytetracycline on lipid peroxidation, antioxidant defense system, paraoxonase (PON1) activities, and homocysteine levels in an animal model of spinal cord injury.

作者信息

Topsakal Cahide, Kilic Nermin, Ozveren Faik, Akdemir Ismail, Kaplan Metin, Tiftikci Murat, Gursu Ferit

机构信息

Department of Neurosurgery, Firat University School of Medicine, Elazig, Turkey.

出版信息

Spine (Phila Pa 1976). 2003 Aug 1;28(15):1643-52. doi: 10.1097/01.BRS.0000083163.03910.B1.

Abstract

STUDY DESIGN

Investigation of the effects of prostaglandin E1, melatonin, and oxytetracycline on lipid peroxidation, antioxidant and paraoxonase activities, and homocysteine levels in an experimental model of spinal cord injury.

OBJECTIVES

To determine the antioxidant efficacy of prostaglandin E1, melatonin, and oxytetracycline and whether paraoxonase and homocysteine can be used as monitoring parameters in the acute oxidative stress of spinal cord injury.

SUMMARY OF BACKGROUND DATA

Melatonin has been found useful in spinal cord injury in previous studies. No study exists investigating the effects of melatonin, prostaglandin E1, and oxytetracycline as well as the response type of paraoxonase enzyme and homocysteine levels in the acute oxidative stress of spinal cord injury.

METHODS

Sixty-three male albino Wistar rats were anesthetized with 400 mg/kg chloral hydrate and divided into 5 groups. The G1 (n = 7) control group provided the baseline levels. G2-G5 underwent T3-T6 total laminectomies and spinal cord injuries by clip compression at the T4-T5 levels. Medications were applied to G3-G5 right after clip compression. Hence, G2 constituted laminectomy + injury, G3 laminectomy + injury + prostaglandin E1; G4 laminectomy + injury + melatonin, and G5 laminectomy + injury + oxytetracycline groups. Animals were decapitated either the first or fourth hour after injury. Spinal cord tissue and blood malonyldialdehyde and plasma homocysteine levels, plasma glutathione peroxidase, superoxide dismutase, paraoxonase activities were assayed. The SPSS 9.0 program was used for statistical analysis and graphics. Intergroup comparisons were made by Bonferroni corrected Mann Whitney U test (P < 0.025) and intragroups comparisons by Wilcoxon Rank test (P < 0.03).

RESULTS

In injury groups, plasma homocysteine levels decreased and paraoxonase activities increased as erythrocyte superoxide dismutase levels and plasma glutathione peroxidase activities decreased in parallel to increases of tissue and blood malonyldialdehyde levels. These alterations were relatively suppressed by prostaglandin E1, melatonin, and oxytetracycline administrations in varying degrees. Melatonin was the most powerful agent, particularly at the fourth hour. Oxytetracycline was also effective, both at the first and fourth hour. Prostaglandin E1 was effective in comparison to injury group, but not as much as melatonin and oxytetracycline.

CONCLUSIONS

Melatonin and oxytetracycline are effective in preventing lipid peroxidation in spinal cord injury. Paraoxonase and homocysteine can be used in monitoring the antioxidant defense system as well as superoxide dismutase and plasma glutathione peroxidase, both in injury and medicated groups.

摘要

研究设计

在脊髓损伤实验模型中研究前列腺素E1、褪黑素和土霉素对脂质过氧化、抗氧化及对氧磷酶活性和同型半胱氨酸水平的影响。

目的

确定前列腺素E1、褪黑素和土霉素的抗氧化功效,以及对氧磷酶和同型半胱氨酸是否可作为脊髓损伤急性氧化应激的监测参数。

背景数据总结

先前研究发现褪黑素对脊髓损伤有用。尚无研究调查褪黑素、前列腺素E1和土霉素的作用,以及对氧磷酶和同型半胱氨酸水平在脊髓损伤急性氧化应激中的反应类型。

方法

63只雄性白化Wistar大鼠用400mg/kg水合氯醛麻醉,分为5组。G1(n = 7)对照组提供基线水平。G2 - G5组行T3 - T6全椎板切除术,并在T4 - T5水平通过夹压造成脊髓损伤。夹压后立即对G3 - G5组给药。因此,G2组为椎板切除术 + 损伤组,G3组为椎板切除术 + 损伤 + 前列腺素E1组;G4组为椎板切除术 + 损伤 + 褪黑素组,G5组为椎板切除术 + 损伤 + 土霉素组。在损伤后第1小时或第4小时将动物断头。测定脊髓组织和血液丙二醛及血浆同型半胱氨酸水平、血浆谷胱甘肽过氧化物酶、超氧化物歧化酶、对氧磷酶活性。使用SPSS 9.0程序进行统计分析和绘图。组间比较采用Bonferroni校正的Mann Whitney U检验(P < 0.025),组内比较采用Wilcoxon秩和检验(P < 0.03)。

结果

在损伤组中,随着组织和血液丙二醛水平升高,红细胞超氧化物歧化酶水平和血浆谷胱甘肽过氧化物酶活性降低,血浆同型半胱氨酸水平降低,对氧磷酶活性升高。这些改变在不同程度上被前列腺素E1、褪黑素和土霉素给药相对抑制。褪黑素是最有效的药物,尤其是在第4小时。土霉素在第1小时和第4小时也有效。与损伤组相比,前列腺素E1有效,但不如褪黑素和土霉素有效。

结论

褪黑素和土霉素可有效预防脊髓损伤中的脂质过氧化。对氧磷酶和同型半胱氨酸可用于监测损伤组和用药组的抗氧化防御系统以及超氧化物歧化酶和血浆谷胱甘肽过氧化物酶。

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