Lithium Protects Against Spinal Cord Injury in Rats: Role of Nitric Oxide
Lithium Protects Against Spinal Cord Injury in Rats: Role of Nitric Oxide
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DOI：
10.1055/s-0033-1345098
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发表时间：
2013-11
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影响因子：
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通讯作者：
Marjan Zakeri;Khashayar Afshari;M. Gharedaghi;R. Shahsiah;R. Rahimian;F. Maleki;A. Dehpour;A. Javidan
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文献类型：
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作者：
Marjan Zakeri;Khashayar Afshari;M. Gharedaghi;R. Shahsiah;R. Rahimian;F. Maleki;A. Dehpour;A. Javidan
摘要目的锂能改善大鼠脊髓损伤后的运动功能。然而，其潜在机制尚不清楚。在此，我们评估一氧化氮（NO）在这一行动中的作用。方法进行第一组实验，以确定锂的剂量，有效地改善运动评分在SCI大鼠。因此，大鼠在SCI前1小时接受不同剂量的氯化锂（1、4、10和20 mg/kg腹腔注射）或生理盐水。在下一步中，研究了NO在锂对SCI的影响中的作用。为此，大鼠用有效剂量的锂（SCI前1小时20 mg/kg）和无效剂量的Nω-硝基-L-精氨酸甲酯（L-NAME，一种非选择性NO合酶抑制剂; SCI前30分钟腹腔内注射15 mg/kg）共同治疗。在麻醉大鼠中，通过用脊髓夹压迫T9脊髓节段60秒来诱导SCI。在SCI后1、3、5、7、14、21和28天测定运动评分。SCI后12小时测量血浆锂水平。脊髓损伤后30天进行脊髓组织病理学检查。结果锂（20 mg/kg）可显著改善大鼠的运动评分，减轻脊髓组织病理学损伤。L-NAME（15 mg/kg）可逆转锂的有益作用。20 mg/kg剂量的锂导致血浆锂浓度为0.68 ± 0.02 mEq/L，低于人体治疗水平（0.8-1.2 mEq/L）。结论锂通过NO依赖性机制保护脊髓损伤。
Abstract Objective Lithium improves locomotor scores after spinal cord injury (SCI) in rats. However, the underlying mechanisms are unknown. Herein, we assess the role of nitric oxide (NO) in this action. Methods The first set of experiments were performed to determine a dose of lithium that effectively improves locomotor scores in rats with SCI. Therefore, rats received different doses of lithium chloride (1, 4, 10, and 20 mg/kg intraperitoneally) or saline 1 hour before SCI. In the next step, the role of NO in the effect of lithium on SCI was investigated. For this purpose, rats were co-treated with an effective dose of lithium (20 mg/kg 1 hour before SCI) and a noneffective dose of Nω-nitro-L-arginine methyl ester (L-NAME, a nonselective NO synthase inhibitor; 15 mg/kg intraperitoneally 30 minutes before SCI). SCI was induced by compressing the T9 spinal segment with an aneurysmal clip for 60 seconds in anesthetized rats. Locomotor scores were determined at 1, 3, 5, 7, 14, 21, and 28 days after SCI. Plasma lithium levels were measured 12 hours after SCI. Spinal histopathologies were examined 30 days after SCI. Results Lithium (20 mg/kg) significantly improved locomotor scores and decreased histopathologic spinal damage. l-NAME (15 mg/kg) reversed the beneficial effects of lithium. The 20-mg/kg dose of lithium resulted in a 0.68 ± 0.02 mEq/L plasma lithium concentration, which is lower than the therapeutic level in humans (0.8–1.2 mEq/L). Conclusion Lithium protects against SCI through an NO-dependent mechanism.