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卵磷脂化超氧化物歧化酶对大鼠脊髓损伤的影响。

Effects of lecithinized superoxide dismutase on rat spinal cord injury.

作者信息

Nakauchi K, Ikata T, Katoh S, Hamada Y, Tsuchiya K, Fukuzawa K

机构信息

Department of Orthopedic Surgery, School of Medicine, University of Tokushima, Japan.

出版信息

J Neurotrauma. 1996 Oct;13(10):573-82. doi: 10.1089/neu.1996.13.573.

Abstract

Although superoxide dismutase (SOD) has been reported to promote functional recovery in ischemic spinal cord injury, it presents many difficulties in practical use primarily due to its short half-life in vivo and low tissue affinity. In this study, we investigated the effects of a new type of SOD, a lecithinized superoxide dismutase (PC-SOD), on motor disturbances, spinal cord edema, levels of myeloperoxidase (MPO), and spinal cord blood flow (SCBF) after spinal cord injury (SCI) in rats. PC-SOD is reported to show a delayed plasma disappearance in vivo in rats and has a higher affinity for vascular endothelium cells, neutrophils, and other cells than unmodified SOD. PC-SOD (4000 units/kg), unmodified SOD (4000 units/kg), or vehicle was injected intravenously 30 min after SCI. Four hours after SCI, SOD activities in spinal cord tissue and plasma were significantly higher in the PC-SOD group than in the unmodified SOD group. In the PC-SOD-treated rats, motor function was significantly better than in the other 2 groups of rats. PC-SOD significantly suppressed MPO activity, an indicator of neutrophils infiltration, in the spinal cord, at 4, 8, and 24 h after SCI, and spinal cord edema at 24 h after SCI. Moreover, the decrease of SCBF after SCI was less marked in the PC-SOD group. The present results suggest that lecithinization can improve the drug delivery of SOD to the spinal cord and PC-SOD may be an alternative pharmacological treatment for SCI.

摘要

尽管超氧化物歧化酶(SOD)已被报道可促进缺血性脊髓损伤后的功能恢复,但由于其在体内半衰期短且组织亲和力低,在实际应用中存在诸多困难。在本研究中,我们调查了一种新型SOD,即卵磷脂化超氧化物歧化酶(PC-SOD)对大鼠脊髓损伤(SCI)后运动障碍、脊髓水肿、髓过氧化物酶(MPO)水平和脊髓血流量(SCBF)的影响。据报道,PC-SOD在大鼠体内血浆消失延迟,并且与未修饰的SOD相比,对血管内皮细胞、中性粒细胞和其他细胞具有更高的亲和力。SCI后30分钟静脉注射PC-SOD(4000单位/千克)、未修饰的SOD(4000单位/千克)或赋形剂。SCI后4小时,PC-SOD组脊髓组织和血浆中的SOD活性显著高于未修饰的SOD组。在接受PC-SOD治疗的大鼠中,运动功能明显优于其他两组大鼠。PC-SOD在SCI后4、8和24小时显著抑制脊髓中中性粒细胞浸润指标MPO的活性,并在SCI后24小时抑制脊髓水肿。此外,PC-SOD组SCI后SCBF的降低不太明显。目前的结果表明,卵磷脂化可以改善SOD向脊髓的药物递送,并且PC-SOD可能是SCI的一种替代药物治疗方法。

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