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英夫利昔单抗在实验性脊髓损伤中的神经保护作用。

Neuroprotective effects of infliximab in experimental spinal cord injury.

作者信息

Kurt Gökhan, Ergün Ertan, Cemil Berker, Börcek Alp Ozgün, Börcek Pelin, Gülbahar Ozlem, Ceviker Necdet

机构信息

Department of Neurosurgery, Gazi University Faculty of Medicine, 06500 Ankara, Turkey.

出版信息

Surg Neurol. 2009 Mar;71(3):332-6, discussion 336. doi: 10.1016/j.surneu.2008.01.038. Epub 2008 Apr 28.

Abstract

BACKGROUND

The aim of the study is to assess the effects of infliximab, a TNF-alpha receptor blocker, in a spinal cord clip compression injury model.

METHODS

Clip compression injury model was used for producing spinal cord injury on 32 adult, male Wistar rats (Gazi University Animal Research Laboratory, Ankara, Turkey). After exposing the vertebral column between T7 and T10, total laminectomy was performed with the assistance of a high-speed drill and a surgical microscope. The dura was left intact. Spinal cord injury was performed on all rats with application of a 70-g closing force aneurysm clip for 1 minute. The rats were randomly allocated into 4 groups. Control group received no further therapy, whereas the other 3 groups received methylprednisolone (30 mg/kg intraperitoneal), infliximab (5 mg/kg subcutaneous), and a mixture of these 2 agents. All rats were killed 72 hours later, and the level of lipid peroxides in traumatized spinal cord tissue were measured as thiobarbituric acid-reactive material and determined using the method of Mihara and Uchiyama (Determination of malonaldehyde precursor in tissue by thiobarbituric acid test. Anal Biochem 1978;86(1):271-8).

RESULTS

Treatment with infliximab and methylprednisolone decreased MDA levels in rats with spinal cord injury with a statistically significant difference. In addition, combined therapy achieved a more profound decrease in tissue MDA levels, which was also statistically significant.

CONCLUSIONS

Infliximab is found as effective as methylprednisolone on spinal cord clip compression injury. Moreover, the combination of these 2 agents demonstrated higher efficacy suggesting a synergistic effect between these 2 agents. However, further studies regarding functional and behavioral analyses as well as biochemical markers are required.

摘要

背景

本研究旨在评估肿瘤坏死因子-α受体阻滞剂英夫利昔单抗在脊髓夹闭压迫损伤模型中的作用。

方法

采用夹闭压迫损伤模型,对32只成年雄性Wistar大鼠(土耳其安卡拉加齐大学动物研究实验室)造成脊髓损伤。暴露T7至T10之间的脊柱后,在高速钻和手术显微镜辅助下进行全椎板切除术。硬脑膜保持完整。对所有大鼠使用70克闭合力的动脉瘤夹夹闭1分钟造成脊髓损伤。将大鼠随机分为4组。对照组不接受进一步治疗,而其他3组分别接受甲基强的松龙(30毫克/千克腹腔注射)、英夫利昔单抗(5毫克/千克皮下注射)以及这两种药物的混合物。72小时后处死所有大鼠,将创伤脊髓组织中的脂质过氧化物水平测定为硫代巴比妥酸反应性物质,并采用Mihara和Uchiyama的方法进行测定(通过硫代巴比妥酸试验测定组织中的丙二醛前体。分析生物化学1978;86(1):271 - 8)。

结果

英夫利昔单抗和甲基强的松龙治疗可降低脊髓损伤大鼠的丙二醛水平,差异具有统计学意义。此外,联合治疗使组织丙二醛水平下降更为显著,差异也具有统计学意义。

结论

发现英夫利昔单抗在脊髓夹闭压迫损伤方面与甲基强的松龙同样有效。此外,这两种药物的联合显示出更高的疗效,表明这两种药物之间存在协同作用。然而,还需要进一步进行功能和行为分析以及生化标志物方面的研究。

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