• 1 遼寧醫(yī)學(xué)院附屬第一醫(yī)院骨科（遼寧錦州，121001）;;
  • 2 錦州市第二醫(yī)院骨科;

目的 氨基胍（aminoguanidine，AG）能顯著減輕腦外傷及中風(fēng)動(dòng)物模型腦水腫，提高神經(jīng)功能恢復(fù)程度。探討AG對(duì)大鼠急性脊髓損傷（spinal cord injury，SCI）后脊髓水腫的作用及相關(guān)機(jī)制。 方法 取成年雄性SD大鼠150只（體重230～255 g），分為對(duì)照組（A組，25只）、假損傷組（B組，25只）、SCI后未治療組（C組，25只）和SCI后AG治療組（75只）；AG治療組按給藥劑量分為AG 75 mg/kg組（D組，25只）、AG 150 mg/kg組（E組，25只）和AG 300 mg/kg組（F組，25只）。A組未行任何處理，B組僅行椎板切除術(shù)但不治療；C、D、E、F組制備靜壓型大鼠SCI模型后，C組腹腔注射5%DMSO，D、E、F組腹腔注射相應(yīng)劑量AG。于造模后0、12、24、48 h用干濕重法檢測(cè)受損脊髓組織含水量以篩選最佳劑量，進(jìn)一步用伊文思蘭（Evans blue，EB）法評(píng)測(cè)血-脊髓屏障功能，用RT-PCR檢測(cè)水通道蛋白4（aquaporins 4，AQP4）mRNA表達(dá)，Western blot和免疫組織化學(xué)染色檢測(cè)AQP4蛋白表達(dá)。 結(jié)果脊髓組織含水量檢測(cè)示，E組在造膜后12、24、48 h對(duì)SCI后脊髓組織水腫有明顯抑制作用（P  lt; 0.05），選擇該劑量組用于后續(xù)實(shí)驗(yàn)。造模后12、24、48 h，E組EB含量明顯低于C組（P  lt; 0.05），降低血-脊髓屏障通透性。RT-PCR檢測(cè)結(jié)果示造模后12、24、48 h，B、E組AQP4 mRNA表達(dá)明顯低于C組；Western blot檢測(cè)示造模后24、48 h，B、E組AQP4蛋白表達(dá)明顯低于C組；免疫組織化學(xué)染色示造模后48 h，B、E組AQP4蛋白表達(dá)明顯低于C組，差異均有統(tǒng)計(jì)學(xué)意義（P  lt; 0.05）；但各指標(biāo)各時(shí)間點(diǎn)B、E組間比較，差異均無統(tǒng)計(jì)學(xué)意義（P  gt; 0.05）。 結(jié)論急性SCI后大鼠經(jīng)150 mg/kg AG治療后，能降低AQP4表達(dá)，改善脊髓水腫，減輕損傷。

引用本文： 范仲凱,曹陽(yáng),張哲,王巖松,于德水,張明超,梅晰凡,呂剛. 氨基胍對(duì)大鼠急性脊髓損傷后脊髓水腫的作用機(jī)制研究. 中國(guó)修復(fù)重建外科雜志, 2012, 26(8): 984-988. doi: 復(fù)制

1. Yang YB, Piao YJ. Effects of resveratrol on secondary damages after acute spinal cord injury in rats. Acta Pharmacol Sin, 2003, 24(7): 703-710.
2. Verkman AS, Ratelade J, Rossi A, et al. Aquaporin-4: orthogonal array assembly, CNS functions, and role in neuromyelitis optica. Acta Pharmacol Sin, 2011, 32(6): 702-710.
3. Wang YF, Fan ZK, Cao Y, et al. 2-Methoxyestradiol inhibits the up-regulation of AQP4 and AQP1 expression after spinal cord injury. Brain Res, 2011, 1370: 220-226 .
4. Sun M, Zhao Y, Gu Y, et al. Neuroprotective actions of aminoguanidine involve reduced the activation of calpain and caspase-3 in a rat model of stroke. Neurochem Int, 2010, 56(4): 634-641.
5. Hao W, Wu XQ, Xu RT. The molecular mechanism of aminoguanidine-mediated reduction on the brain edema after surgical brain injury in rats. Brain Res, 2009, 1282: 156-161.
6. Xu WB, Lv G, Wang YF, et al. Combination of dexamethasone and aminoguanidine reduces secondary damage in compression spinal cord injury. Cell Mol Neurobiol, 2009, 29(5): 683-689.
7. Manley GT, Fujimura M, Ma T, et al. Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nat Med, 2000, 6(2): 159-163.
8. Marsala M, Hefferan MP, Kakinohana O, et al. Measurement of peripheral muscle resistance in rats with chronic ischemia-induced paraplegia or morphine-induced rigidity using a semi-automated computer-controlled muscle resistance meter. J Neurotrauma, 2005, 22(11): 1348-1361.
9. Huang WL, George KJ, Ibba V, et al. The characteristics of neuronal injury in a static compression model of spinal cord injury in adult rats. Eur J Neurosc, 2007, 25(2): 362-372.
10. Yu Y, Matsuyama Y, Nakashima S, et al. Effects of MPSS and a potent iNOS inhibitor on traumatic spinal cord injury. Neuroreport, 2004, 15(13): 2103-2107.
11. Di F, Yan-Ting G, Hui L, et al. Role of aminoguanidine in brain protection in surgical brain injury in rat. Neurosci Lett, 2008, 448(2): 204-207.
12. Xu M, Su W, Xu QP. Aquaporin-4 and traumatic brain edema. Chin J Traumatol, 2010, 13(2): 103-110.
13. Yang B, Zador Z, Verkman AS. Glial cell aquaporin-4 overexpression in transgenic mice accelerates cytotoxic brain swelling. J Biol Chem, 2008, 283(22): 15280-15286.
14. Papadopoulos MC, Verkman AS. Aquaporin-4 and brain edema. Pediatr Nephrol, 2007, 22(6): 778-784.
15. Nesic O, Lee J, Ye Z, et al. Acute and chronic changes in aquaporin 4 expression after spinal cord injury. Neuroscience, 2006, 143(3): 779-792.
16. Saadoun S, Bell BA, Verkman AS, et al. Greatly improved neurological outcome after spinal cord compression injury in AQP4-deficient mice. Brain, 2008, 131(Pt 4): 1087-1098.
17. Galea E, Regunathan S, Eliopoulos V, et al. Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine. Biochem J, 1996, 316(Pt 1): 247-249.
18. Zhu SM, Xiong XX, Zheng YY, et al. Propofol inhibits aquaporin 4 expression through a protein kinase C-dependent pathway in an astrocyte model of cerebral ischemia/reoxygenation. Anesth Analg, 2009, 109(5): 1493-1499.
19. Tang Y, Cai D, Chen Y. Thrombin inhibits aquaporin 4 expression through protein kinase C-dependent pathway in cultured astrocytes. J Mol Neurosci, 2007, 31(1): 83-93.
20. Gunnarson E, Zelenina M, Axehult G, et al. Identification of a molecular target for glutamate regulation of astrocyte water permeability. Glia, 2008, 56(6): 587-596.
  1. 1. Yang YB, Piao YJ. Effects of resveratrol on secondary damages after acute spinal cord injury in rats. Acta Pharmacol Sin, 2003, 24(7): 703-710.
  2. 2. Verkman AS, Ratelade J, Rossi A, et al. Aquaporin-4: orthogonal array assembly, CNS functions, and role in neuromyelitis optica. Acta Pharmacol Sin, 2011, 32(6): 702-710.
  3. 3. Wang YF, Fan ZK, Cao Y, et al. 2-Methoxyestradiol inhibits the up-regulation of AQP4 and AQP1 expression after spinal cord injury. Brain Res, 2011, 1370: 220-226 .
  4. 4. Sun M, Zhao Y, Gu Y, et al. Neuroprotective actions of aminoguanidine involve reduced the activation of calpain and caspase-3 in a rat model of stroke. Neurochem Int, 2010, 56(4): 634-641.
  5. 5. Hao W, Wu XQ, Xu RT. The molecular mechanism of aminoguanidine-mediated reduction on the brain edema after surgical brain injury in rats. Brain Res, 2009, 1282: 156-161.
  6. 6. Xu WB, Lv G, Wang YF, et al. Combination of dexamethasone and aminoguanidine reduces secondary damage in compression spinal cord injury. Cell Mol Neurobiol, 2009, 29(5): 683-689.
  7. 7. Manley GT, Fujimura M, Ma T, et al. Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke. Nat Med, 2000, 6(2): 159-163.
  8. 8. Marsala M, Hefferan MP, Kakinohana O, et al. Measurement of peripheral muscle resistance in rats with chronic ischemia-induced paraplegia or morphine-induced rigidity using a semi-automated computer-controlled muscle resistance meter. J Neurotrauma, 2005, 22(11): 1348-1361.
  9. 9. Huang WL, George KJ, Ibba V, et al. The characteristics of neuronal injury in a static compression model of spinal cord injury in adult rats. Eur J Neurosc, 2007, 25(2): 362-372.
  10. 10. Yu Y, Matsuyama Y, Nakashima S, et al. Effects of MPSS and a potent iNOS inhibitor on traumatic spinal cord injury. Neuroreport, 2004, 15(13): 2103-2107.
  11. 11. Di F, Yan-Ting G, Hui L, et al. Role of aminoguanidine in brain protection in surgical brain injury in rat. Neurosci Lett, 2008, 448(2): 204-207.
  12. 12. Xu M, Su W, Xu QP. Aquaporin-4 and traumatic brain edema. Chin J Traumatol, 2010, 13(2): 103-110.
  13. 13. Yang B, Zador Z, Verkman AS. Glial cell aquaporin-4 overexpression in transgenic mice accelerates cytotoxic brain swelling. J Biol Chem, 2008, 283(22): 15280-15286.
  14. 14. Papadopoulos MC, Verkman AS. Aquaporin-4 and brain edema. Pediatr Nephrol, 2007, 22(6): 778-784.
  15. 15. Nesic O, Lee J, Ye Z, et al. Acute and chronic changes in aquaporin 4 expression after spinal cord injury. Neuroscience, 2006, 143(3): 779-792.
  16. 16. Saadoun S, Bell BA, Verkman AS, et al. Greatly improved neurological outcome after spinal cord compression injury in AQP4-deficient mice. Brain, 2008, 131(Pt 4): 1087-1098.
  17. 17. Galea E, Regunathan S, Eliopoulos V, et al. Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine. Biochem J, 1996, 316(Pt 1): 247-249.
  18. 18. Zhu SM, Xiong XX, Zheng YY, et al. Propofol inhibits aquaporin 4 expression through a protein kinase C-dependent pathway in an astrocyte model of cerebral ischemia/reoxygenation. Anesth Analg, 2009, 109(5): 1493-1499.
  19. 19. Tang Y, Cai D, Chen Y. Thrombin inhibits aquaporin 4 expression through protein kinase C-dependent pathway in cultured astrocytes. J Mol Neurosci, 2007, 31(1): 83-93.
  20. 20. Gunnarson E, Zelenina M, Axehult G, et al. Identification of a molecular target for glutamate regulation of astrocyte water permeability. Glia, 2008, 56(6): 587-596.