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α-生育酚对大鼠脊髓再灌注损伤血管并发症的潜在保护作用。

A potential protective effect of alpha-tocopherol on vascular complication in spinal cord reperfusion injury in rats.

机构信息

Physiology Department, College of Medicine, Menoufiya University, Egypt.

出版信息

J Biomed Sci. 2010 Jul 7;17(1):55. doi: 10.1186/1423-0127-17-55.

Abstract

BACKGROUND

Paraplegia remains a potential complication of spinal cord ischemic reperfusion injury (IRI) in which oxidative stress induced cyclooxygenase activities may contribute to ischemic neuronal damage. Prolonged administration of vitamin E (alpha-TOL), as a potent biological antioxidant, may have a protective role in this oxidative inflammatory ischemic cascade to reduce the incidence of paraplegia. The present study was designed to evaluate the preventive value of alpha-TOL in IRI of spinal cord.

METHODS

For this study, 50 male Sprague-Dawley rats were used and divided into five experimental groups (n = 10): Control group (C); alpha-TOL control group (CE) which received intramuscular (i.m.) alpha-TOL injections (600 mg/kg); Sham operated group (S), IRI rats were subjected to laparotomy and clamping of the aorta just above the bifurcation for 45 min, then the clamp was released for 48 hrs for reperfusion; and IRIE rats group, received 600 mg/kg of alpha-TOL i.m. twice weekly for 6 weeks, followed by induction of IRI similar to the IRI group. At the end of the experimental protocol; motor, sensory and placing/stepping reflex evaluation was done. Plasma nitrite/nitrate (NOx) was measured. Then animals' spinal cord lumbar segments were harvested and homogenized for measurement of the levels of prostaglandin E2 (PGE2), malondialdehyde (MDA) and advanced oxidation products (AOPP), while superoxide dismutase (SOD) and catalase (CAT) activity were evaluated.

RESULTS

Induction of IRI in rats resulted in significant increases in plasma levels of nitrite/nitrate (p < 0.001) and spinal cord homogenate levels of PGE2, MDA, advanced oxidation protein products AOPP and SOD with significant reduction (p < 0.001) in CAT homogenate levels. Significant impairment of motor, sensory functions and placing/stepping reflex was observed with IRI induction in the spinal cord (p < 0.001). alpha-TOL administration in IRIE group significantly improved all the previously measured parameters compared with IRI group.

CONCLUSIONS

alpha-TOL administration significantly prevents the damage caused by spinal cord IRI in rats with subsequent recovery of both motor and sensory functions. Alpha-tocopherol improves the oxidative stress level with subsequent reduction of the incidence of neurological deficits due to spinal cord IRI conditions.

摘要

背景

脊髓缺血再灌注损伤(IRI)仍然是截瘫的潜在并发症,其中氧化应激诱导的环氧化酶活性可能导致缺血性神经元损伤。维生素 E(α-TOL)的长期给药,作为一种有效的生物抗氧化剂,可能在这种氧化炎症性缺血级联反应中发挥保护作用,降低截瘫的发生率。本研究旨在评估α-TOL 在脊髓 IRI 中的预防价值。

方法

本研究使用 50 只雄性 Sprague-Dawley 大鼠,分为五组(n = 10):对照组(C);α-TOL 对照组(CE),肌肉内注射(i.m.)α-TOL(600mg/kg);假手术组(S),仅行剖腹术和主动脉分叉上方夹闭 45min,然后夹闭 48 小时再灌注;IRIE 组,每周两次肌肉内注射 600mg/kg α-TOL 6 周,然后进行类似 IRI 组的 IRI 诱导。在实验方案结束时;进行运动、感觉和放置/踏步反射评估。测量血浆中亚硝酸盐/硝酸盐(NOx)水平。然后采集动物的腰椎脊髓段并匀浆,以测量前列腺素 E2(PGE2)、丙二醛(MDA)和高级氧化蛋白产物(AOPP)的水平,同时评估超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的活性。

结果

在大鼠中诱导 IRI 导致血浆中亚硝酸盐/硝酸盐水平显著升高(p < 0.001),脊髓匀浆中 PGE2、MDA、高级氧化蛋白产物 AOPP 和 SOD 水平显著升高(p < 0.001),而 CAT 匀浆水平显著降低(p < 0.001)。在脊髓中诱导 IRI 后,运动、感觉功能和放置/踏步反射明显受损(p < 0.001)。IRIE 组给予α-TOL 治疗后,与 IRI 组相比,所有上述测量参数均显著改善。

结论

α-TOL 治疗可显著预防大鼠脊髓 IRI 引起的损伤,随后恢复运动和感觉功能。α-生育酚可改善氧化应激水平,从而降低脊髓 IRI 引起的神经功能缺损发生率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74c9/2909177/f3721bbf3b54/1423-0127-17-55-1.jpg

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