氨基胍對大鼠急性脊髓損傷后脊髓水腫的作用機制研究_《中國修復重建外科雜志》

作者：

范仲凱 ¹ , 曹陽 ¹ , 張哲 ² , 王巖松 ¹ , 于德水 ¹ , 張明超 ¹ , 梅晰凡 ¹ , 呂剛 ¹

1 遼寧醫學院附屬第一醫院骨科（遼寧錦州，121001）;;
2 錦州市第二醫院骨科;

關鍵詞：

急性脊髓損傷脊髓水腫氨基胍水通道蛋白4 大鼠

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目的氨基胍（aminoguanidine，AG）能顯著減輕腦外傷及中風動物模型腦水腫，提高神經功能恢復程度。探討AG對大鼠急性脊髓損傷（spinal cord injury，SCI）后脊髓水腫的作用及相關機制。方法取成年雄性SD大鼠150只（體重230～255 g），分為對照組（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組腹腔注射相應劑量AG。于造模后0、12、24、48 h用干濕重法檢測受損脊髓組織含水量以篩選最佳劑量，進一步用伊文思蘭（Evans blue，EB）法評測血-脊髓屏障功能，用RT-PCR檢測水通道蛋白4（aquaporins 4，AQP4）mRNA表達，Western blot和免疫組織化學染色檢測AQP4蛋白表達。結果脊髓組織含水量檢測示，E組在造膜后12、24、48 h對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實驗。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檢測結果示造模后12、24、48 h，B、E組AQP4 mRNA表達明顯低于C組；Western blot檢測示造模后24、48 h，B、E組AQP4蛋白表達明顯低于C組；免疫組織化學染色示造模后48 h，B、E組AQP4蛋白表達明顯低于C組，差異均有統計學意義（P lt; 0.05）；但各指標各時間點B、E組間比較，差異均無統計學意義（P gt; 0.05）。結論急性SCI后大鼠經150 mg/kg AG治療后，能降低AQP4表達，改善脊髓水腫，減輕損傷。

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

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. 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.

《中國修復重建外科雜志》

氨基胍對大鼠急性脊髓損傷后脊髓水腫的作用機制研究

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《中國修復重建外科雜志》

氨基胍對大鼠急性脊髓損傷后脊髓水腫的作用機制研究

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

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