참고문헌김종오, 남궁욱, 서태범, 오명진, 윤진환.(2009). 척수좌상후트레드밀운동이피질척수로의재생및신경생리학적기능회복에미치는영향. 한국생활환경학회지, 16(2): 윤진환, 서태범, 진낙식, 김종오, 지용석, 임은미, 최승오, 이희혁 (2008). 유

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1 트레드밀운동에의한 MAPK 관련전사인자활성화가축삭재생과탈신경된가자미근의비대에 미치는효과 윤진환. 정일규. 김연희 한남대학교 Abstract 초 록 Yoon, J.H., Jeong, I.G., Kim, Y.H. Effects of axonal regeneration and hypertrophy in denervated soleus muscle on MAPK-regulated transcription factors activated by treadmill exercise. Exercise Science, 00(0):00-00, The main objective of this study was to investigate the effect of exercise-activated ErK1/2 and c-jun pathway on axonal regeneration and hypertrophy of denervated soleus muscle. Rats were randomly divided into three groups: control group (n=60), sedentary group after sciatic nerve injury (n=60, sedentary group 1, 3, 7, 14, 21 and 28 after injury) and treadmill exercise group after sciatic nerve injury (n=60, exercise group 1, 3, 7, 14, 21 and 28 after injury. Two days after injury, animals in the exercise group were forced to run on treadmill for 30 min once a day for 5 consecutive days. present result demonstrated that treadmill exercise further increased axonal regrowth in the region 10 mm distal to the injury site from 14 days post injury and upregulated GAP-43 induction levels than those in the sedentary group 28 days after injury. expression levels of p-erk1/2 and p-c-jun were significantly increased in treadmill training compared to the sedentary group 3 and 7 days after injury. Treadmill exercise after sciatic nerve injury not only prevented atrophy of the soleus muscle but also significantly increased cross-sectional area of the skeletal muscle at 21 and 28 days. The present data suggest that increased p-erk1/2 and p-c-jun by treadmill exercise may play an important role in the axonal regeneration and skeletal muscle hypertrophy after sciatic nerve injury. 본연구의목적은운동에의한 Erk1/2와 c-jun 경로의활성화가축삭재생과탈신경된가자미근의비대에미치는영향을분석하는것이다. 총 180마리의 S.D계쥐들을무작위로 3개의그룹으로나누었다. 통제그룹 (n=60), 좌골신경손상후비운동그룹 (n=60, 좌골신경손상 1, 3, 7, 14, 21 그리고 28일후비운동그룹 ) 그리고좌골신경손상후트레드밀운동그룹 (n=60, 좌골신경손상 1, 3, 7, 14, 21 그리고 28일후운동그룹 ) 이다. 손상 2일후운동그룹에쥐들은하루에 30분씩하루에한번주 5일동안트레드밀달리기를수행하였다. 본연구는트레드밀운동이비운동그룹보다손상 14일후부터 10 mm 원위부에서의축삭재생이증가하였고, 손상 28일에는 GAP-43 단백질의발현이촉진되었다. p-erk1/2 and p-c-jun의발현수준은손상 3 그리고 7일후비운동그룹에비해운동그룹에서통계적으로유의하게증가하였다. 좌골신경손상 21 그리고 28일후트레드밀운동은가자미근의위축을억제할뿐만아니라골격근의횡단면적을통계적으로유의하게증가시켰다. 결론적으로, 트레드밀운동에의해증가된 p-erk1/2 and p-c-jun은좌골신경손상후축삭의재생과골격근의비대를조절하는중요한역할을수행할것이다. Key words : soleus, devervation. MAPK, Erk1/2, c-jun, sciatic, treadmill, 주요어 : 트레드밀운동, 축삭재생, 좌골신경손상, 가자미근 비대 이논문은 2009 년도국민체육진흥공단체육과학연구원의체육학술진흥사업비에의하여연구되었음 (06/KISS-09-A06006)

2 참고문헌김종오, 남궁욱, 서태범, 오명진, 윤진환.(2009). 척수좌상후트레드밀운동이피질척수로의재생및신경생리학적기능회복에미치는영향. 한국생활환경학회지, 16(2): 윤진환, 서태범, 진낙식, 김종오, 지용석, 임은미, 최승오, 이희혁 (2008). 유산소성운동이쥐의좌골신경손상후슈완세포의기능적활동성에관한생체내. 외연구. 한국체육학회지, 47: Abe, J.I., Kusuhara, M., Ulevitch, R.J., Berk, B.C., & Lee, J.D. (1996). Big mitogen-activated protein kinase 1(BMK1) is a redox-sensitive kinase. Journal of Biological Chemistry. 271: Aronson, D., Dufresne, S.D., & Goodyear, L.J. (1997). Contractile activity stimulates the c-jun NH2-terminal kinase pathway in rat skeletal muscle. Journal of Biological Chemistry. 272: Cotman, C. W., & Berchtold, N.C. (2002). Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci., 25: Deak, M., Clifton, A., Lucocq, L., & Alessi, D. (1998). Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB. EMBO Journal. 15: Dock, W. (1994). The evil sequlae of complete bed rest. J. A. M. A., 125: Fawcett, J.W. (2001). Peripheral nerve regeneration, in: Brain Damage, Brain Repair. J.W. Fawcett, A.E. Rosser, and S.B. Dunnett (eds), Oxford University Press: New York, Gigo-Benato, D., Geuna, S., de Castro Rodrigues, A.l. (2004). Lowpower laser biostimulation enhances nerve repair after end-toside neurorrhaphy: a double-blind randomized study in the rat median nerve model. Lasers Med Sci., 19: Han, I.S., Seo, T.B., Kim, K.H., Yoon, J.H., Yoon, S.J., & Namgung, U. (2007). Cdc2-mediated Schwann cell migration during peripheral nerve regeneration.j Cell Sci., 15: Herdegen, T., Skene, P., & Bähr, M. (1997). The c-jun transcription factor--bipotential mediator of neuronal death, survival and regeneration. Trends Neurosci., 20(5): Ilha, J., Araujo, R.T., Malysz, T., Hermel, E.E., Rigon, P., Xavier, L.L., & Achaval, M. (2008). Endurance and resistance exercise training programs elicit specific effects on sciatic nerve regeneration after experimental traumatic lesion in rats. Neurorehabil Neural Repair., 22(4): Irintchev, A., Carmody, J., & Wernig, A. (1991). Effects on recovery of soleus and extensor digitorum longus muscle of prolonged wheel running during a period of repeated nerve damage. Neuroscience. 44: Jaweed, M.M., Herbison, G.J., & Diturnno, J.F. (1974). Effect of swimming on compensatory hypertrophy of reinnernernng soleus and plantarjf.muscle. Am J Phys Med., 53: : Johnson, G.L. & Lapadat, R. (2002). Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science. 298: Kasper, C. T. & Maxwell, W.L. (1990). Running during recovery from hindlimb suspension induces muscular injury. J. Appl. Physiol., 68(2): Long, Y.C., Widegren, U., & Zierath, JR. (2004). Exercise-induced mitogen-activated protein kinase signalling in skeletal muscle. Proc Nutr Soc., 63: Matsuura, T., Ikata, T., & Takata, S. (2001). Effect of weight bearing on recovery from nerve injury in skeletal muscle. J Appl Physiol., 91: Mendonça, A.C., Barbieri, C.H., & Mazzer, N. (2003). Directly applied low intensity direct electric current

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4 and muscle contraction. Acta Physiologica Scandinavica. 172: Widegren, U., Wretman, C., Lionikas, A., Westerblad, H. & Henriksson, J. (2000). Influence of exercise intensity on ERK/MAP kinase signalling in human skeletal muscle. Pflugers Archives European Journal of Physiology, 441: Wretman, C., Lionikas, A., Widegren, U., Lannergren, J., Westerblad, H., & Henriksson, J. (2001). Effects of concentric and eccentric contractions on phosphorylation of MAPKerk1/2 and MAPKp38 in isolated rat skeletal muscle. Journal of Physiology (London), 535: Yu, M., Stepto, N.K., Chibalin, A.V., Fryer, L.G.D., Carling, D., Krook, A., Hawley, J.A., & Zierath, J.R. (2003). Metabolic and mitogenic signal transduction in human skeletal muscle after intense cycling exercise. Journal of Physiology (London), 546: 그림. 1. 좌골신경손상후지속적인트레드밀운동은원위부에서의축삭재생을촉진시킨다. (a) 10 mm 원위부에서 neurofilament-200 항체에염색된재성장하는축삭. 3일까지는모든그룹에서재성장하는축삭을확인할수없었다. 14일후부터트레드밀운동그룹에서재성장하는축삭의양이증가하였다. (b) 축삭의재생이가장활발한 28일에서재생의지표인 GAP-43 단백질의발현확인. 트레드밀운동그룹에서 GAP-43 단백질의발현이증가하였다. dpc, days post crush; seden, sedentary; GAP-43, growth-assocaited protein 43.

p-erk1/2, phosphorylated-erk1/2; seden, sedentary; TMT, treadmill training; DPC, days post crush. 그림. 3.

5 그림. 2. 트레드밀운동에의한 Erk1/2 단백질인산화촉진. 손상된좌골신경에서단백질을추출한후 western blot 을 수행하였다. p-erk1/2 의발현량은손상 3 그리고 7 일후트레드밀운동그룹에서통계적으로유의하게증가하 였다. p-erk1/2, phosphorylated-erk1/2; seden, sedentary; TMT, treadmill training; DPC, days post crush. 그림. 3. 트레드밀운동에의한 c-jun 단백질인산화촉진. 손상된좌골신경에서단백질을추출한후 western blot 을수 행하였다. p-c-jun 단백질은손상후 3, 7 일에만유일하게발현되었다. p-c-jun 의발현량은손상 3 그리고 7 일 후트레드밀운동그룹에서통계적으로유의하게증가하였다. p-c-jun, phosphorylated-c-jun.

6 그림. 4. 트레드밀운동에의한골격근섬유비대. 좌골신경손상후적출된가자미근을횡단면으로절편한후 eosin 염색을수행하였다. 좌골신경손상 21 일과 28 일후트레드밀운동그룹에서가자미근섬유의크기가통계적으 로유의하게증가하였다.

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경락경혈학회지 Vol.27, No.1, pp.87 106, 2010 Journal of Meridian & Acupoint Dept. of 1 Meridian & Acupoint, 3 Acupuncture & Moxibustion, College of Oriental Medicine, Daejeon University 2 Division of Clinical