Effect of Aqueous Extract of Sukjiyanggeun-Tang(shudiyangjin-tang) on Functional Recovery and Expressions of Inflammatory Mediators after Sciatic Nerve Crushed Injury in Rat

숙지양근탕(熟地養筋湯) 추출물이 흰쥐 좌골신경 손상 후에 기능회복과 염증 매개 인자 발현에 미치는 영향

  • Jang, Gun ;
  • Song, Yun-Kyoung ;
  • Lim, Hyung-Ho
  • 장건 ;
  • 송윤경 ;
  • 임형호
  • Published : 2013.04.30


Objectives : Peripheral nerve injuries are commonly encountered clinical problems and often result in severe functional deficits. Sukjiyanggeun-Tang(shudiyangjin-tang), in oriental medicine, has been used to treat various musculoskeletal disorders. Methods : In the present study, the effects of aqueous extract of Sukjiyanggeun-Tang(shudiyangjin-tang) on functional recovery, severity of pain, and expressions of neurofilament, cycloxygenease-2(COX-2), inducible nitric oxide synthase(iNOS), and tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) following sciatic crushed nerve injury in rats were investigated. For this study, walking tract analysis, plantar test, western blot analysis for COX-2 iNOS, and TNF-${\alpha}$, and Immunofluorescence test for neurofilament were performed. Results : In the present results, sciatic functional index(SFI) in walking tract analysis was significantly decreased following sciatic crushed nerve injury, and pain severity in plantar test was significantly increased. COX-2, iNOS and TNF-${\alpha}$ expressions were increased whereas neurofilament expression was decreased by sciatic crushed nerve injury, In contrast, treatment with Sukjiyanggeun-Tang(shudiyangjin-tang) improved SFI in walking tract analysis and suppressed the pain severity in sciatic crushed nerve injury. Sukjiyanggeun-Tang(shudiyangjin-tang) treatment also suppressed COX-2, iNOS, and TNF-${\alpha}$ expressions and enhanced the neurofilament expression in sciatic crushed nerve injury. Conclusions : In the present study, we have shown that Sukjiyanggeun-Tang(shudiyangjin-tang) is the effective therapeutic modality to ameliorate the symptoms of sciatic crushed nerve injury.


Sukjiyanggeun-Tang(shudiyangjin-tang);Sciatic nerve injury;Axonal Regeneration;Sciatic functional index;COX-2;iNOS;TNF-${\alpha}$


  1. Molina-Holgado E, Ortiz S, Molina-Holgado F, Guaza C. Induction of COX-2 and PGE2 biosynthesis by IL-1${\beta}$ is mediated by PKC and mitogen-activated protein kinases in murine astrocytes. Br J Pharmacol. 2000;131(1):152-9. https://doi.org/10.1038/sj.bjp.0703557
  2. Hla T, Neilson K. Human cyclooxygenase-2 cDNA. Proc Natl Acad Sci USA. 1992;89(16):7384-8. https://doi.org/10.1073/pnas.89.16.7384
  3. Hirschberg DL, Yoles E, Belkin M, Schwartz M. Inflammation after axonal injury has conflicting consequences for recovery of function: rescue of spared axons is impaired but regeneration is supported. J Neuroimmunol. 1994;50(1):9-16. https://doi.org/10.1016/0165-5728(94)90209-7
  4. Richardson PM, Lu X. Inflammation and axonal regeneration. J Neurol. 1994;242(1 Suppl 1):57-60. https://doi.org/10.1007/BF00939244
  5. Takahashi M, Kawaguchi M, Shimada K, Konishi N, Furuya H, Nakashima T. Cyclooxygenase-2 expression in Schwann cells and macrophages in the sciatic nerve after single spinal nerve injury in rats. Neurosci Lett. 2004;363(3):203-6. https://doi.org/10.1016/j.neulet.2004.03.040
  6. Moalem G, Tracey DJ. Immune and inflammatory mechanisms in neuropathic pain.Brain Res Rev. 2006;51(2):240-64. https://doi.org/10.1016/j.brainresrev.2005.11.004
  7. Levy D, Höke A, Zochodne DW. Local expression of inducible nitric oxide synthase in an animal model of neuropathic pain. Neurosci Lett. 1999;260(3):207-9. https://doi.org/10.1016/S0304-3940(98)00982-3
  8. Yoon HJ, Moon ME, Park HS, Im SY, Lee JH, Kim YH. Effects of chitosanoligosaccharide on the Calbicans-induced Inflammatory effect in mice and RAW264.7 macrophage cells. J Chitin Chitosan. 2007;12:15-20.
  9. Li H, Lin X. Positive and negative signaling components involved in TNF alpha-induced NF-kappaB activation.Cytokine. 2008;41(1):1-8. https://doi.org/10.1016/j.cyto.2007.09.016
  10. Schafers M, Geis C, Brors D, Yaksh TL, Sommer C. Anterograde transport of tumor necrosis factor-alpha in the intact and injured rat sciatic nerve. J Neurosci. 2002;22(2):536-45.
  11. DuBois RN, Awad J, Morrow J, Roberts LJ 2nd, Bishop PR. Regulation of eicosanoid production and mitogenesis in rat intestinal epithelial cells by transforming growth factor-alpha and phorbol ester. J Clin Invest. 1994;93(2):493-8. https://doi.org/10.1172/JCI116998
  12. Masferrer JL, Zweifel BS, Manning PT, Hauser SD, Leahy KM, Smith WG, Isakson PC, Seibert K. Selective inhibition of inducible cyclooxygenase 2 in vivo is antiinflammatory and nonulcerogenic. Proc Natl Acad Sci USA. 1994;91(8):3228-32. https://doi.org/10.1073/pnas.91.8.3228
  13. Seibert K, Zhang Y, Leahy K, Hauser S, Masferrer J, Perkins W, Lee L, Isakson P. Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. Proc Natl Acad Sci USA. 1994;91(25):12013-7. https://doi.org/10.1073/pnas.91.25.12013
  14. Funakoshi H, Frisén J, Barbany G, Timmusk T, Zachrisson O, Verge VM, Persson H. Differential expression of mRNAs for neurotrophins and their receptors after axotomy of the sciatic nerve. J Cell Biol. 1993;123(2):455-65. https://doi.org/10.1083/jcb.123.2.455
  15. Hulsebosch CE. Recent advances in pathophysiology and treatment of spinal cord injury. Adv Physiol Educ. 2002;26(1-4):238-55. https://doi.org/10.1152/advan.00039.2002
  16. 김길훤 김완희. 운동부하후의 피로회복에 미치는 補中益氣湯 및 六味地黃湯의 효과. 동의생리학회지. 1987;2(1):1-13.
  17. Shenn JJ, Lin CJ, Huang JL, Hsieh KH, Kuo ML. The effect of liu-wei-di-huang wan on cytokine gene expression from human peripheral blood lymphocytes. Am J Chin Med. 2003;31(2):247-57. https://doi.org/10.1142/S0192415X03000886
  18. Koka R, Hadlock TA. Quantification of functional recovery following rat sciatic nerve transection. Exp Neurol. 2001;168(1):192-5. https://doi.org/10.1006/exnr.2000.7600
  19. 최명애, 안경주. DHEA 투여가 일측성 말초 신경 손상에 의해 유발된 신경병증성 통증 쥐의 환측과 정상측 뒷다리근에 미치는 영향. 대한간호학회지. 2009;39:632-40.
  20. Sato J, Perl ER. Adrenergic excitation of cutaneous pain receptors induced by peripheral nerve injury. Science. 1991;251(5001):1608-10. https://doi.org/10.1126/science.2011742
  21. Malin SA, Molliver DC, Hoerber BC, Cornuet BC, Fyre R, Albers KM, Davis BM. Glial cell line-derived neurotrophic factor family members sensitize nociceptors in vitro and produce thermal hyperalgesia in vivo. J Neurosci. 2006;26(33):8588-99. https://doi.org/10.1523/JNEUROSCI.1726-06.2006
  22. Fawcett JW. Peripheral nerve regeneration in Brain damage, Brain repair, edited by JW Fawcett, AE Rosser, SB Dunnett. NY:Oxford University Press. 2001:143-45.
  23. Akassoglou K, Yu WM, Akpinar P, Strickland S. Fibrin inhibits peripheral nerve regeneration by arresting Schwann cell differentiation. Neuron. 2002;33(6):861-75. https://doi.org/10.1016/S0896-6273(02)00617-7
  24. Zhang JY, Luo XG, Xian CJ, Liu ZH, Zhou XF. Endogenous BDNF is required for myelination and regeneration of injured sciatic nerve in rodents. Eur J Neurosci. 2000;12(12):4171-80.
  25. Scholz J, Woolf CJ. The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci. 2007;10(11):1361-8. https://doi.org/10.1038/nn1992
  26. Janeway CA Jr, Medzhitov R. Innate immune recognition. Annu Rev Immunol. 2002;20:197-216. https://doi.org/10.1146/annurev.immunol.20.083001.084359
  27. Hoffmann JA, Kafatos FC, Janeway CA, Ezekowitz RA. Phylogenetic perspectives in innate immunity. Science. 1999;284(5418):1313-8. https://doi.org/10.1126/science.284.5418.1313
  28. 박희제, 배기상, 김도윤, 서상완, 박경배, 김병진, 송제문, 이경용, 나철, 신병철, 박성주, 송호준, 황성연. LPS로 자극한 RAW264.7세포에서 강활 추출물의 염증성세포활성물질의 억제효과. 대한본초학회. 2008;23(3):127-34.
  29. 조재헌, 김건식, 차재덕, 이현삼, 최현, 정혁상, 손낙원, 손영주. 두충이 좌골신경손상 흰쥐의 후지 근육위축에 미치는 영향. 동의생리병리학회지. 2008;22(6):1454-61.
  30. 이수정, 김송백, 최창인, 이기상, 조한백, 최창민. 목과의 항염 및 면역반응에 대한 실험적 연구. 대한한방부인과학회지. 2008;21(4):36-48.
  31. 이금홍, 강신성, 안원근, 이영선, 권영규, 신상우. 補血 藥材인 당귀, 지황, 백작약, 하수오의 면역 촉진 효과 비교 분석. 동의생리병리학회지. 2006;20(6):1507-15.
  32. 배항, 명유진, 강희, 심범상, 김성훈, 최승훈, 안규석. 보기약물인 인삼, 황기, 백출, 감초의 물 추출액이 생쥐 면역세포의 Cytokine분비에 미치는 영향. 동의생리병리학회지. 2005;19(1):69-74.
  33. Dellon AL, Mackinnon SE. Sciatic nerve regeneration in the rat. Validity of walking track assessment in the presence of chronic contractures. Microsurgery. 1989;10(3):220-5. https://doi.org/10.1002/micr.1920100316
  34. Hargreaves K, Dubner R, Brown F, Flores C, Joris J. A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain. 1988;32(1):77-88. https://doi.org/10.1016/0304-3959(88)90026-7
  35. Warner MA, Warner DO, Harper CM, Schroeder DR, Maxson PM. Lower extremity neuropathies associated with lithotomy positions. Anesthesiology. 2000;93(4):938-42. https://doi.org/10.1097/00000542-200010000-00010
  36. Poppi M, Giuliani G, Gambari PI, Acciarri N, Gaist G, Calbucci F. A hazard of craniotomy in the sitting position: the posterior compartment syndrome of the thigh. J Neurosurg. 1989;71(4):618-9. https://doi.org/10.3171/jns.1989.71.4.0618
  37. 대한침구학회 교재편찬위원회. 침구학 下. 서울:집문당. 2008:176-8.
  38. Fawcett JW, Keynes RJ. Peripheral nerve regeneration. Annu Rev Neurosci. 1990;13:43-60. https://doi.org/10.1146/annurev.ne.13.030190.000355
  39. Stoll G, Müller HW. Nerve injury, axonal degeneration and neural regeneration: basic insights. Brain Pathol. 1999;9(2):313-25.
  40. 안혜림, 양미성, 신미숙, 최진봉, 김선종. 좌골 신경 압좌 손상 후 전침 및 녹용 약침의 통증 감소와 신경 재생에 관한 실험적 연구. 한방재활의학과학회지. 2009;19(1):39-55.
  41. 양미성, 신미숙, 안혜림. 흰쥐 좌골신경 압좌 손상 후 오약순기산 및 전침이 신경손상의 회복에 미치는 영향. 한방재활의학과학회지. 2008;18(4):25-37.
  42. 송정섭, 나철, 신병철, 이수경, 권영달, 송용선. 흰쥐 좌골신경 압좌 손상 후 독활탕 및 중성어혈약침이 통증 억제와 신경 재생에 미치는 효과. 한방재활의학과학회지. 2008;18(2):61-79.
  43. 강준혁, 오민석. 흰쥐의 좌골신경축삭 압좌 손상 후 시호 추출물에 의한 재생반응성 개선효과. 대한한의학회지. 2010;31(1):93-111.
  44. 이마성, 송윤경, 임형호. 우슬 추출물이 흰쥐 좌골신경 손상 후 좌골신경의 기능회복에 미치는 영향. 한방재활의학과학회지. 2011;21(2):143-58.
  45. 조재헌, 김건식, 차재덕, 이현삼, 최현, 정혁상, 손낙원, 손영주. 두충이 좌골신경손상 흰쥐의 후지 근육위축에 미치는 영향. 동의생리병리학회지. 2008;22(6):1454-61.
  46. 장승욱, 김연섭. 갈근이 좌골신경 손상 흰쥐의 후지 근육 위축에 미치는 영향. 동의생리병리학회지. 2009;23(2).405-11.
  47. Cho HC, Song YK, Lim HH. Effects of Gentianae Macrophyllae Radix on the functional recovery and expression of BDNF and c-FOS after sciatic crushed nerve injury in rats. The Journal of Korean Oriental Medicine. 2009;30(3):28-38.
  48. Cho TY, Song YK, Lim HH. The effects of aqueous extracts of Aconiti ciliare tuber on functional recovery after sciatic crushed nerve injury in rats. The Journal of Korean Oriental Medicine. 2009;30(3):39-50.
  49. Kim JH, Seol IC, Ryu HR, Jo HK, An JJ, Namgung U, Kim YS. Facilitated Axonal Regeneration of Injured Sciatic Nerves by Yukmijihwang-tang Treatment. Korean J. Oriental Physiology & Pathology. 2008;22(4):896-902.
  50. 윤성식, 김철중, 조충식. 사물제통탕이 Taxol 처리 및 좌골신경 압좌 손상 후 신경조직 변 화에 미치는 영향. 대한한방내과학회지. 2012;33(2):126-44.
  51. 은영준, 송윤경, 임형호. 해인탕 추출물이 흰쥐 좌골신경 손상 모델에서 기능회복과 뇌의 c-Fos 발현에 미치는 영향. 한방재활의학과학회지. 2011;21(2):125-42.
  52. Choi SP, Song YK, Lim HH. Effects of bee venom and sweet bee venom acupuncture on functional recovery and c-Fos expression in the brain after sciatic crushed nerve injury in rats. The Journal of Korean Oriental Medicine. 2010;31(3):79-97.
  53. Lee MK, Song YK, Lim HH. Effects of acupuncture at GB30, GB34 and BL40 on functional recovery after sciatic crushed nerve injury in rats. The Journal of Korean Oriental Medicine. 2010;31(3):66-78.
  54. 홍순성, 오민석. 당귀가 rat의 손상된 좌골신경 재생에 미치는 영향. 대한한의학회지. 2008;29(2):133-50.
  55. 김형석, 노정두. 육계약침액이 LPS로 유도된 대식세포의 염증반응에 미치는 영향. 대한침구학회지. 2012;29(1):15-24.
  56. 정선희, 박동석. 附子藥鍼이 鎭痛 및 消炎作用에 미치는 影響. 대한침구학회지. 1997;14(1):334-46.
  57. 최원주, 김기봉, 김경호, 김장현. 급성통증 유발 흰쥐에 대한 威靈仙藥鍼의 통증 억제효과. 대한침구학회지. 2009;26(6):91-100.
  58. Lee YS, Lee GH, Kwon YK, Lee IK, Xue CC, Li CG, Lee SY, Shin SW. Anti-inflammatory and Anti-allergic Effects of Lycii Fructurs Extract. Korean J. Oriental Physiology & Pathology. 2005;19(5):1386-90.
  59. 김태한, 이병렬, 이현, 임윤경. 足三里 白芷藥鍼이 collagen-induced arthritis에 미치는 영향. 경락경혈학회지. 2007;24(3):179-204.
  60. Dahlin LB. The biology of nerve injury and repair. J Am Soc Surg Hand 2004;4(3):143-55. https://doi.org/10.1016/j.jassh.2004.06.006
  61. 김진일, 최명애. 일측성 좌골신경손상이 쥐의 정상측 뒷다리근에 미치는 영향. 대한간호학회지. 2009;39(3):393-400.
  62. Hyun JK, Lee SJ, Yoo DS, Park HG, Kwon BS. The electrodiagnostic findings of sciatic nerve injury according to the locations and etiologies. J Korean Acad Rehabil Med. 2004;28(1):54-8.
  63. Park KC, Kim KW, Kim YH. Combined femoral and sciatic nerve palsy associated with acetabular fracture and dislocation-A case report. J Kor Fracture Soc. 2005;18:341-4. https://doi.org/10.12671/jkfs.2005.18.3.341
  64. Mu MM, Chakravortty D, Sugiyama T, Koide N, Takahashi K, Mori I, Yoshida T, Yokochi T. The inhibitory action of quercetin on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophage cells. J Endotoxin Res. 2001;7(6):431-8. https://doi.org/10.1179/096805101101533034
  65. Ryu JH, Ahn H, Kim JY, Kim YK. Inhibitory activity of plant extracts on nitric oxide synthesis in LPS-activated macrophage. Phytother Res. 2003;17(5):485-9. https://doi.org/10.1002/ptr.1180
  66. Rodríguez FJ, Cabré AV, Navarro X. Regeneration and functional recovery following peripheral nerve injury. Drug Discov Today: Disease Models. 2004;1(2):177-85. https://doi.org/10.1016/j.ddmod.2004.09.008
  67. 박혜상, 박준선. 흰쥐의 좌골신경 압좌손상 후 저강도 레이저 치료가 이질통에 미치는 영향. 체육과학연구. 2009;20:29-36.
  68. Lee SK, Wolfe SW. Peripheral nerve injury and repair. J Am Acad Orthop Surg. 2000;8(4):243-52. https://doi.org/10.5435/00124635-200007000-00005