氨基胍对大鼠急性脊髓损伤后脊髓水肿的影响
[Effect of aminoguanidine on spinal cord edema of acute spinal cord injury in rats].
作者信息
Fan Zhongkai, Cao Yang, Zhang Zhe, Wang Yansong, Yu Deshui, Zhang Mingchao, Mei Xifan, Lü Gang
机构信息
Department of Orthopedics, First Affiliated Hospital, Liaoning Medical College, Jinzhou Liaoning 121001, PR China.
出版信息
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2012 Aug;26(8):984-8.
OBJECTIVE
Aminoguanidine (AG) can reduce brain edema and increase the recovery of neuron functions in surgical brain injury and stroke. To investigate the effect of AG on spinal cord injury (SCI) in rats and its mechanism.
METHODS
A total of 150 adult male Sprague Dawley rats (weighing, 230-255 g) were divided into control group (group A, 25 rats without treatment), the sham-operated group (group B, 25 rats undergoing laminectomy), SCI group (group C, 25 SCI rats with injection of 5% DMSO), SCI + AG groups (groups D, E, and F, 25 SCI rats and AG injection of 75, 150, and 300 mg/kg, respectively). The optimal dosage of AG was screened by dry-wet weight method with the percentage of water content at 0, 12, 24, and 48 hours after injury. The blood-spinal cord barriar permeability was further detected by Evans blue (EB) method, aquaporins 4 (AQP4) mRNA expression by RT-PCR, AQP4 protein expression by immunohistochemistry and Western blot.
RESULTS
AG injection at dosage of 150 mg/kg can significantly reduce edema of spinal cords at 12, 24, and 48 hours after SCI (P < 0.05), so 150 mg/kg was the optimal dosage. The EB content in group E was significantly lower than that in group C at 12, 24, and 48 hours after SCI, and the permeability of blood-spinal cord barrier was significantly decreased compared with group C (P < 0.05). The AQP4 mRNA expressions in groups B and E were significantly lower than that in group C at 12, 24, and 48 hours after SCI (P < 0.05). AQP4 protein expressions in groups B and E were significantly lower than that in group C at 24 and 48 hours after SCI (P < 0.05) by Western blot. Immunohistochemical staining revealed that AQP4 protein expression in group C was significantly higher than that in groups B and E (P < 0.05) at 48 hours after SCI, but no significant difference was found between group B and group E (P > 0.05).
CONCLUSION
AG injection at dosage of 150 mg/kg can induce spinal cord edema and injury in rats, which could be correlated with the down-regulation of AQP4 expression.
目的
氨基胍（AG）可减轻脑损伤和中风手术中的脑水肿并促进神经元功能恢复。本研究旨在探讨AG对大鼠脊髓损伤（SCI）的影响及其机制。
方法
将150只成年雄性Sprague Dawley大鼠（体重230 - 255 g）分为对照组（A组，25只未处理）、假手术组（B组，25只接受椎板切除术）、SCI组（C组，25只SCI大鼠注射5%二甲基亚砜）、SCI + AG组（D、E、F组，25只SCI大鼠分别注射75、150和300 mg/kg的AG）。采用干湿重法，通过检测损伤后0、12、24和48小时的含水量百分比来筛选AG的最佳剂量。采用伊文思蓝（EB）法进一步检测血脊髓屏障通透性，采用逆转录聚合酶链反应（RT-PCR）检测水通道蛋白4（AQP4）mRNA表达，采用免疫组织化学和蛋白质免疫印迹法检测AQP4蛋白表达。
结果
注射150 mg/kg的AG可显著减轻SCI后12、24和48小时的脊髓水肿（P < 0.05），因此150 mg/kg为最佳剂量。SCI后12、24和48小时，E组的EB含量显著低于C组，血脊髓屏障通透性与C组相比显著降低（P < 0.05）。SCI后12、24和48小时，B组和E组的AQP4 mRNA表达显著低于C组（P < 0.05）。蛋白质免疫印迹法显示，SCI后24和48小时，B组和E组的AQP4蛋白表达显著低于C组（P < 0.05）。免疫组织化学染色显示，SCI后48小时，C组的AQP4蛋白表达显著高于B组和E组（P < 0.05），但B组和E组之间无显著差异（P > 0.05）。
结论
注射150 mg/kg的AG可减轻大鼠脊髓水肿和损伤，这可能与AQP4表达下调有关。
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