Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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The Effect of Swimming and Minocycline on Motor Function and Expression of Bcl-2 after Spinal Cord Injury in the Rats

미노싸이클린과 수영훈련이 척수손상 흰쥐의 운동기능 및 Bcl-2발현에 미치는 영향

  • Ha, Mi-Sook (Department of Physical Therapy, Msan University) ;
  • Ha, Bae-Jin (Department of Pharmaceutical Eingineering, Silla University)
  • Published : 2009.10.30
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Abstract

This study was designed to investigate the effects of swimming and minocycline on motor function recovery and Bcl-2 expression after spinal cord injury (SCI) in rats. After operation, neurological motor behavior test (BBB scale) on days 1, 4, 7, 10, and 14 were tested. Western blot and immunohistochemical assessment (Bcl-2) were performed on day 14. BBB scale started to show a statistically significant difference on day 7 (p<0.05). On day 14, it showed the most significant (p<0.05) difference. Expression of Bcl-2 increased in all the experimental groups. In particular, the highest expression of Bcl-2 appeared in the swimming and minocycline groups. Based on these results, minocycline and swimming were the most effective factors in the motor behavior function and immunohistochemical assessment of SCI rats.

본 연구는 척수 앞뿔의 세포손상을 준 흰쥐를 대상으로 수영운동과 미노싸이클린의 치료적 중재를 통해 운동기능과 신경계의 회복을 알아보고 운동에 의한 척수손상의 신경학적 회복기전을 밝히는 것의 목적이 있다. 본 연구의 진행은 Sprague-Dawley계 흰쥐 28마리의 허리뼈 1-2번 사이에 6-OHDA로 척수손상을 일으킨 다음 3일 후에 치료를 시작하였다. 수영은 주 5회 15분간 운동을 실시하고 미노싸이클린은 척수손상을 유발한 후 12시간마다 복강내 주입하였다. 척수손상을 유발한 후 치료를 시작하기 전에 운동기능의 평가를 시행하며 2주 동안 4번의 검사가 이루어졌으며, Bcl-2 발현에 관한 측정은 2주간 치료 후 검사하였다. BBB 척도에서 대조군에 비해 실험군에서 7일에 차이가 있었으며, 14일에는 II, III군에 비해 실험군 Ⅳ군에서 증가하였다. Bcl-2의 면역학적 소견에서 실험군 모두 대조군에 비해 척수 앞뿔에서 Bcl-2의 발현이 증가되었으며, 실험군 Ⅳ에서 가장 많은 Bcl-2의 발현이 관찰되었다. 척수손상 후 미노싸이클린과 수영은 행동학적, 면역학적 소견을 긍정적으로 개선시키는 것으로 나타났으며, 수영과 미노싸이클린을 함께 실시한 경우 세포사멸의 감소와 운동기능의 회복에 효과가 있음을 알 수 있었다.

Keywords

References

  1. Andoniou, C. E., D. M. Andrews, M. Manzur, P. Ricciardi-Castagnoli, and M. A. Degli-Esposti. 2004. A novel checkpoint in the Bel-2-regulated apoptotic pathway revealed by murine cytomegalovirus infection of dendritic cells. J. Cell BioI. 166, 827-837 https://doi.org/10.1083/jcb.200403010
  2. Antonsson, B. and J. C. Martinou. 2000. The Bcl-2 protein family. Exp. Cell Res. 256, 50-57 https://doi.org/10.1006/excr.2000.4839
  3. Arvin, K. L., B. H. Han, Y. Du, S. Z. Lin, S. M. PauL and D. M. Holtzman. 2002. Minocyeline markedly protects the neonatal brain against hypoxic-ischemic injury. Ann. Neural. 52, 54-61 https://doi.org/10.1002/ana.10242
  4. Bracken, M. B. and T. R. Holford. 2002. Neurological and functional status 1 year after acute spinal cord injury: Estimates of functional recovery in National Acute Spinal Cord Injury Study II from results modeled National Acute Spinal Cord Injury Study III. J. Neurasurg. 96, 259-266
  5. Buchholz, A. C. and P. B. Pencharz. 2004. Energy expenditure in chronic spinal cord injury. Curro Opin. Clin. Natr. Metab. Care. 7, 635-639 https://doi.org/10.1097/00075197-200411000-00008
  6. Chen, M., V. O. Ona, M. Li, R J. Rerrante, K. B. Fink, S. Zuh, J. Bian, L. Guo, L. A. Farrell, S. M. Hersch, W. Hobbs, J. P. Vonsattet J. H. Cha, and R M. Friedlander. 2000. Minocycline inhibits caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat. Med. 6, 797-801 https://doi.org/10.1038/77528
  7. DeVries, A. C., H. D. Joh, O. Bernard, K. Hattori, P. D. Hum, R J. Traystman, and N. J. Alkayed. 2001. Social stress exacerbates stroke outcome by suppressing Bcl-2 expression. Proc. Natl. Acad. Sci. USA 98, 11824-11828 https://doi.org/10.1073/pnas.201215298
  8. Donovan, M. and T. G. Cotter. 2004. Control of mitochondrial integrity by Bcl-2 family members and caspase independent cell death. Biochim. Biophys. Acta. 1644, 133-147 https://doi.org/10.1016/j.bbamcr.2003.08.011
  9. Engesser-Cesar, C., A. J. Anderson, D. M. Basso, V. R. Edgerton, and C. W. Cotman. 2005. Voluntary wheel running improves recovery from a moderate spinal cord injury. J. Neurotrauma. 22, 157-171 https://doi.org/10.1089/neu.2005.22.157
  10. Gupta, S. 2001. Molecular steps of death receptor and mitochondrial pathways of apoptosis. Life Sci. 69, 2957-2964 https://doi.org/10.1016/S0024-3205(01)01404-7
  11. Hattori, R, T. E. Hemande, L. Zhu, N. Maulik, H. Otani, and Y. Kaneda. 2001. An essential role of the antioxidant gen Bcl-2 in myocardial adaptation to ischemia: an insight with antisense Bcl-2 therapy. Anioxid Redox Signal. 3, 403-413 https://doi.org/10.1089/15230860152409059
  12. He, Y., S. Appet and W. Le. 2001. Minocycline inhibits microglial activation and protects nigral cells after 6-hydroxydopamine injection into mouse striatum. Brain Res. 909, 187-193 https://doi.org/10.1016/S0006-8993(01)02681-6
  13. Kakulas, B. A. 2004. Neuropathology: the foundation for new treatments in spinal cord injury. J. Spinal Cord Med. 42, 549 https://doi.org/10.1038/sj.sc.3101670
  14. Kim, C. K. and H. S. Lee. 2003. Effect of rehabilitation sports program on self-efficacy, Sport understanding and sport participation in spinal cord injury persons. Journal of Sport and Leisure Studies. 20, 773-781
  15. Kim, C. S., D. Nkajima, C. Y. Yang, T. W. Oh, S. Igawa, M. Miyazaki, H. Fukuoka, and F. Ohta. 2000. Prolonged swimming exercise training induce hypophosphatemic osteopenia in stroke-prone spontaneously htpertensive rats(SH R S P). J. Physio. Anthropol. Appl. Human Sci. 19, 271-277 https://doi.org/10.2114/jpa.19.271
  16. Kim, D. J. 2008. The effect of aquatic rehabilitation exercise program on serum lipids and atherogenic indices in the disabiled people with spinal cord injury. J. Life Sci. 18, 724-730
  17. Lee, S. M., T. Y. Yune, S. J. Kim, D. W. Park Y. K. Lee, Y. C. Kim, Y. J. Oh, G. J. Markelonis, and T. H. Oh. 2003. Minocycline reduces cell death and improves functional recovery after traumatic spinal cord injury in the rat. J. Neurotrauma. 2, 1017-1027
  18. Molteni, R, Z. Ying, and F. Gomez-Pirilla. 2002. Differential effects of acute and chronic exercise on plasticity-related genes in the rat hippocampus revealed by microarray. European J. Neuroscience 16, 1107-1116 https://doi.org/10.1046/j.1460-9568.2002.02158.x
  19. Raghavendra, V., F. Tanga, and J. A. DeLeo. 2003. Inhibition of microglial activa-tion attenuates the development but not existing hypersensitivity in a rat model of neuropathy. J. Pharmacol. Exp. Ther. 306, 624-630 https://doi.org/10.1124/jpet.103.052407
  20. Sanchez Mejia R, O., V. O. Ona, M. Li, and R. M. Friedlander. 2001. Minocycline reduces traumatic brain injury-mediated caspase-1 actvation, tissue damage, and neurological dysfunction. Neurosurgery 48, 1393-1399 https://doi.org/10.1097/00006123-200106000-00051
  21. Scheff, S. W., D. A. Saucier, and M. E. Cain. 2002. A statistical method for analyzing rating scale data: the BBB locomotor score. J. Neurotrauma. 19, 1251-1260 https://doi.org/10.1089/08977150260338038
  22. Stirling, D. P., K. Khodarahmi, J. Liu, L. T. McPhail, C. B. McBride, J. D. Steeves, M. S. Ramer, and W. Tetzlaff. 2004. Minocycline treatment reduces delayed oligodendr ocyte death, attenuates axonal die-back, and improves functional outcome after spinal cord injury. J. Neurosci. 24, 2182-2190 https://doi.org/10.1523/JNEUROSCI.5275-03.2004
  23. Teng,. Y. D., H. Choi, R. C. Onario, S. Zhu, F. C. Desilets, S. Lan, E. J. Woodard, E. Y. Snyder, M. E. Eichler, and R. M. Friedlander. 2004. Minocycline inhibits contusion triggered mitochondrial cytochrome c release and mitigatesfunctional deficits after spinal cord injury. Proc. Natl. A cad. Sci. USA 101, 3071-3076 https://doi.org/10.1073/pnas.0306239101
  24. Vegran, F., R Boidot, C. Oudin, J. M. Riedinger, and S. Lizard-Nacol. 2005. Implication of alternative splice transcripts of caspase-3 and survivin in chemoresistance. Bull. Canser 92, 219-226 https://doi.org/10.1038/sj.bjc.6600153
  25. Woo, H. J., H. J. Kim, S. H. Hong, S. H. Hong, B. T. Choi, Y. T. Lee, D. I. Park, and Y. H. Choi. 2007. Induction of apoptosis by bee venom in A549 human lung epithelial cancer cells through modulation of Bcl-2 and activation of caspases. J. Life Sci. 17, 1596-1600
  26. Yang, Y. R. and P. S. Wang. 2003. Early and late treadmill training after focal brain ischemia in rats. Neurosic. Lett. 339, 91-94 https://doi.org/10.1016/S0304-3940(03)00010-7
  27. Zurita, M., J. Vaquero, S. Oya, and C. Morales. 2002. Effects of dexamethasone on apoptosis-related cell death after spinal cord injury. J. Neurosurg. 96, 83-89