Effects of Scutellariae Radix on Neuronal Apoptosis of Spinal Cord Contusion Injury in Rats

황금(黃芩)이 척수압박손상 흰쥐의 척수신경세포 자연사에 미치는 영향

  • Bahn, Hyo-Jung (Dept. of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung-Hee University) ;
  • Jo, Jong-Jin (Dept. of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung-Hee University) ;
  • Kim, Bum-Hoi (Dept. of Anatomy, College of Oriental Medicine, Dong-Eui University) ;
  • Park, Seong-Ha (Dept. of Internal Medicine, School of Korean Medicine, Pusan National University) ;
  • Shin, Jung-Won (Dept. of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung-Hee University) ;
  • Kim, Seong-Joon (Dept. of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung-Hee University) ;
  • Sohn, Nak-Won (Dept. of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung-Hee University)
  • 반효정 (경희대학교 동서의학대학원 한의과학전공) ;
  • 조종진 (경희대학교 동서의학대학원 한의과학전공) ;
  • 김범회 (동의대학교 한의과대학 해부학교실) ;
  • 박성하 (부산대학교 한의학전문대학원 한방내과학교실) ;
  • 신정원 (경희대학교 동서의학대학원 한의과학전공) ;
  • 김성준 (경희대학교 동서의학대학원 한의과학전공) ;
  • 손낙원 (경희대학교 동서의학대학원 한의과학전공)
  • Received : 2011.05.04
  • Accepted : 2011.09.23
  • Published : 2011.10.30

Abstract

Objectives : This Study was performed to evaluate the effects of Scutellariae Radix(SR) water-extract on the tissue and neuronal apoptosis of the spinal cord injury(SCI). Methods: SCI was induced by mechanical contusion following laminectomy of 10th thoracic vertebra in Sprague-Dawley rats. SR was orally given once a day for 7 days after SCI. Neuronal apoptosis was examined with terminal deoxynucleotidyl transferase-mediated dUTPnick-end labeling(TUNEL) assay. Bax (Bcl-2-asociated X protein), Bcl-2(B-cell blastoma 2), c-Fos(FBJ osteosarcoma oncogene) expressions were examined using immuno-histochemistry. Individual TUNEL and immuno-labeled cells expressing Bax, Bcl-2 and c-Fos were counted on the same level in peri-damaged region and in ventral horn. Results: 1. SR significantly reduced number of TUNEL labeled apoptotic cells induced by the spinal cord contusion injury. 2. SR significantly reduced Bax positive cells expression on the motor neuron in the ventral horn induced by the spinal cord contusion injury. 3. SR strengthened Bcl-2 expression on the motor neuron in the ventral horn induced by the spinal cord contusion injury. 4. SR reduced c-Fos expression on the motor neuron in the ventral horn induced by the spinal cord contusion injury. Conclusions : These results suggest that SR plays an inhibitory role against neuronal apoptosis and has significant effects for locomotor disfunction induced by SCI.

References

  1. 대한정형외과학회. 정형외과학. 서울:최신의학사. 2004:675-8.
  2. 대한척추신경외과학회. 척추학. 서울:군자출판사. 2008:553-63.
  3. 강원기. 척수압박. 대한내과학회지. 1998;55(4):557-62.
  4. 이현삼, 정혁상, 강철훈, 손낙원. 廣豆根이 백서 중대뇌동맥 폐쇄에 의한 국소뇌허혈 손상에 미치는 영향. 대한한의학회지. 2000;20(2):68-78.
  5. 김경훈, 박동완, 정승현, 신길조, 손낙원, 이원철. 청열도담당이 Mongolian Gerbil의 가역성 전뇌허혈 모델에 미치는 영향. 한방성인병학회지. 2001;7(1):41-52.
  6. 이민영, 구자승, 김성훈, 김윤범, 김선여, 최현, 손영주, 정혁상, 손낙원. 淸肺潟肝湯이 뇌해마 조직배양의 신경세포 자연사에 미치는 영향. 동의생리병리학회지. 2008;22(4):771-7.
  7. 박은경, 심은섭, 정혁상, 손낙원, 손영주. 총명탕, 원지, 석창포가 베타아밀로이드로 유발된 학습과 기억장애에 미치는 영향. 대한한방내과학회지. 2008;29(3):608-20.
  8. 이주용, 구자승, 이동은, 신정원, 김성준, 손낙원. 天麻가 뇌조직출현 흰쥐의 뇌부종과 Aquaporins 발현에 미치는 영향. 대한본초학회지. 2010;25(4):85-93.
  9. 한영수, 오민석. 흰쥐의 척수손상 후 천궁처리에 의한 피질척수로 축삭재생반응시 Glial cells의 역할. 한방재활의학과학회지. 2008;18(3):19-39.
  10. 박원상, 김은석, 신정원, 김범회, 김성준, 강희, 손낙윈. 狗脊이 흰쥐의 척수압박에 의한 신경세포 손상에 미치는 영향. 한방재활의학과학회지. 2010;20(2):1-15.
  11. 성주원, 김기역, 반효정, 신정원, 강희, 김성준, 손낙원. 황련해독탕이 척수 압박손상 흰쥐의 운동기능 장애에 미치는 영향. 항방재활의학과학회지. 2010;20(4):1-15.
  12. 김호철. 한약약리학. 서울:집문당. 2001:129-33.
  13. 김석창, 안건석, 박채규, 전병선, 이종태, 박원종. 황금으로부터 항산화 활성 성분의 분리. 한국약용작물학회지. 2006;14(4):212-6.
  14. 이병철, 임강현, 김영옥, 김선려, 안덕규, 박호군, 김호철. 황금의 4-VO로 유발한 흰쥐 뇌허혈에 대한 신경방어효과. 대한본초학회지. 1999;14(2):89-96.
  15. 김완식, 정승현, 신길조, 문일수, 이원철. 흰쥐 대뇌세포의 저산소증 모델에서 黃芩에 의한 신경세포사 저해 효과. 생명과학회지. 2007;17(1):143-9.
  16. Liu C, Wu J, Xu K, Cai F, Gu J, Ma L, Chen J. Neuroprotection by baicalein in ischemic brain injury involves PTEN/AKT pathway. J Neurochem. 2010;112(6):1500-12. https://doi.org/10.1111/j.1471-4159.2009.06561.x
  17. Tu XK, Yang WZ, Shi SS, Wang CH, Chen CM. Neuroprotective effect of baicalin in a rat model of permanent focal cerebral ischemia. Neurochem Res. 2009;34(9):1626-34. https://doi.org/10.1007/s11064-009-9953-4
  18. Piao HZ, Jin SA, Chun HS, Lee JC, Kim WK. Neuroprotective effect of wogonin: potential roles of inflammatory cytokines. Arch Pharm Res. 2004;27(9):930-6. https://doi.org/10.1007/BF02975846
  19. Young W. Spinal cord contusion models. Prog Brain Res. 2002;137:231-55.
  20. 孫星衍. 神農本草經. 臺北:文光圖書有限公司. 1982:149-50.
  21. 김동찬, 노승현, 이상인, 이영종, 주영승. 방제학. 서울:영림사. 1990:111-3, 263-4.
  22. 國家中醫藥管理局. 中華本草. 上海:上海科學技術出版社. 1998:1682-94.
  23. Kim YO, Leem K, Park J, Lee P, Ahn DK, Lee BC, Park HK, Suk K, Kim SY, Kim H. Cytoprotective effect of Scutellaria baicalensis in CA1 hippocampal neurons of rats after global cerebral ischemia. J Ethnopharmacol. 2001;77(2-3):183-8. https://doi.org/10.1016/S0378-8741(01)00283-5
  24. Heo H, Shin Y, Cho W, Choi Y, Kim H, Kwon YK. Memory improvement in ibotenic acid induced model rats by extracts of Scutellaria baicalensis. J Ethnopharmacol. 2009;122(1):20-7. https://doi.org/10.1016/j.jep.2008.11.026
  25. Kim DS, Kim JY, Han YS. Alzheimer's disease drug discovery from herbs: neuroprotectivity from beta-amyloid (1-42) insult. J Altern Complement Med. 2007;13(3):333-40. https://doi.org/10.1089/acm.2006.6107
  26. Schwab JM, Brechtel K, Mueller CA, FailliV, Kaps HP, Tuli SK et al. Experimental strategies to promote spinal cord regeneration-an integrative perspective. Prog Neurobiol. 2006;78:91-116. https://doi.org/10.1016/j.pneurobio.2005.12.004
  27. Tator CH. Biology of neurological recovery and functional restoration after spinal cord injury. Neurosurgery. 1998;42:696-707. https://doi.org/10.1097/00006123-199804000-00007
  28. Nicholson DW. Mechanisms of apoptotic control. Nature. 2000;407:810-6. https://doi.org/10.1038/35037747
  29. Love S, Hilton DA. Comparison of methods for the detection of cells indifferent stages of apoptosis. Neuropathol Appl Neurobiol. 1996;22:161-2.
  30. Chen J, Zhu RL, Nakayama M. Expression of the apoptosis-effector gene, BAX is upregulated in vulnerable hippocampal CA1 neurons following global ischemia. J Neurochem. 1996;67:64-71.
  31. Gillardon F, Wickert H, Zimmermann M. Up-regulation of Bax and down-regulation of Bcl-2 is associated with kainate-induced apoptosis in mouse brain. Neurosci Lett. 1995;192:85-8. https://doi.org/10.1016/0304-3940(95)11619-8
  32. Hara A, Iwai T, Niwa, M. Immunohistochcmical detection of BAX and BCI-2 proteins in gerbil hippocampus following transient forebrain ischemia. Brain Res. 1996;711:249-53. https://doi.org/10.1016/0006-8993(95)01436-5
  33. Kinouchi H, Sharp FR, Chen PH, Koistinaho J, Sagar SM, Yoshimoto T: induction of c-fos, junB, c-jun, and hsp70 mRNA in cortex, thalamus, basal ganglia, and hippocampus following middle cerebral artery occlusion. J Cereb Blood Flow Metab. 1994;14:808-17. https://doi.org/10.1038/jcbfm.1994.101
  34. Menetrey D, Gannon A, Levine JD, Basbaum AI. Expression of c-fos protein in interneurons and projection neurons of the rat spinal cord in response to noxious somatic, articular, and visceral stimulation. J Comp Neurol. 1989;285:177-95. https://doi.org/10.1002/cne.902850203