동의신경정신과학회지 (Journal of Oriental Neuropsychiatry)

  • 제20권1호
  • /
  • Pages.177-197
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  • 2009
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  • 1226-6396(pISSN)
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  • 2234-4942(eISSN)
대한한방신경정신과학회 (The Korean Society of Oriental Neuropsychiatry)
권호 표지

인삼(人蔘)이 허혈성 중추신경 손상으로 발현 증가된 CD81 및 GFAP에 미치는 영향

The Effect of the Radix Ginseng on Expression of CDSI and GFAP Following Hypoxic Injury on Central Nervous System

  • 서중훈 (원광대학교 한의학전문대학원 한약자원개발학과) ;
  • 송봉근 (원광대학교 한의과대학 내과학교실) ;
  • 류영수 (원광대학교 한의과대학 신경정신과 교실) ;
  • 강형원 (원광대학교 한의과대학 신경정신과 교실) ;
  • 김태헌 (원광대학교 한의과대학 신경정신과 교실)
  • Seo, Jong-Hoon (Professional Graduate School of Oriental Medicine, Wonkwang University) ;
  • Song, Bong-Gun (Department of Internal Medicine, Wonkwang University Oriental Medical School) ;
  • Lyu, Yeoung-Su (Dept. of Neoropsychiatry, College of Oriental Medicine, Wonkwang University) ;
  • Kang, Hyung-Won (Dept. of Neoropsychiatry, College of Oriental Medicine, Wonkwang University) ;
  • Kim, Tae-Heon (Dept. of Neoropsychiatry, College of Oriental Medicine, Wonkwang University)
  • 발행 : 2009.03.30
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초록

Objectives : Gliosis disturbs recovery of damaged astrocytes following central nervous system(CNS) injury. Gliosis relates to up-regulation of CD81 and GFAP. In glial cells at injured CNS, the expression of CD81 and GFAP is increased. It is possible that when the gliosis formation is suppressed, regeneration of oxons can occur. According to the recent study, the treatment with anti CD81 antibodies enhanced functional recovery in rats with spinal injury. So, the author studies the effect of water extract of Radix Ginseng on regulation of CD81 and GFAP with CNS injury. Methods : In the cell study, hypoxic damage was induced by CoC12. And according to Longa et al, cerebral ischemia was made by middle cerebral artery occlusion in the rat. Cross sections of rat brain were examined under microscope. MTT analysis was performed to examine cell viability, cell based ELISA, Western Blot and PCR were used to detect the expression of CD81 and GFAP. Results : The following results were obtained. 1. We found that CD81 and GFAP were decreased in hypoxic injured cells following Radix Ginseng administration. 2. We injected the extract of Radix Ginseng to the middle cerebral artery occlusion in rats, and the immunohistochemistry analysis showed that CDS1 and GFAP were decreased. Conclusions : These results show that the extract of Radix Ginseng could suppress the gliosis formation and prevent cell death, by controlling the expression of CDS1 and GFAP. Therefore, Radix Ginseng could be a useful to regenerate CNS injury.

키워드

참고문헌

  1. 대한노인병학회 저. 노인병학. 서울: 도서출판 의학출판사. 2002:67-71.
  2. 이원택, 박경아. 의학신경해부학. 서울: 고려의학. 1996:118-22, 673-7.
  3. Fawcett JW, Asher RA. The glial scar and CNS repair. Brain Res Bull. 1999;9(6):377-91.
  4. Pekny M, Nilsson M. Astrocyte activation and reactive gliosis. GLIA. 2005;50:427-34. https://doi.org/10.1002/glia.20207
  5. Dijkstra S, Geisert EE Jr, Gipsen WH, Bar PR, Joosten EAJ. Up-regulation of CD81(target of the antiproliferative antibody; TAPA) by reactive microglia and astrocytes after spinal cord injury in the rat. J Comp Neurol. 2004;428:266-77.
  6. Geisert EE Jr, Yang L, Irwin MH. Astrocyte growth, reactivity, and the target of the antiproliferative antibody, TAPA. J Neurosci. 1996;16(17):5478-87.
  7. Geisert EE Jr, Abel HJ, Fan L, Geisert GR. Retinal pigment Epithelium of the rat express CD81, the target of the antiproliferative antibody(TAPA). Invest Ophthalmol & Vis Sci. 2002;43(1):274-80.
  8. Song BK, Geisert GR, Vazquez-Chona F, Giesert EE Jr. Temporal regulation of CD81 followng retinal injury in the rat. Neurosci Lett. 2003;338(1):29-32. https://doi.org/10.1016/S0304-3940(02)01364-2
  9. Dijkstra S, Duis S, Pans IM, Lankhorst AJ, Hamers FPT, Veldman H, Bar PR, ispen WH, Joosten EA, Geisert EE Jr. Intraspinal administration of an antibody against CD81 enhances functional recovery and tissue sparing after experimental spinal cord injury. Exp Neurol. 2006;202(1):57-66. https://doi.org/10.1016/j.expneurol.2006.05.011
  10. Geisert EE Jr, Williams RW, Geisert GR, Fan L, Asbury AM, Maecker HT, Deng J, Levy S. Increased brain size and glial cell number in CD81-null mice. J Comp Neurol 2002;453:22-32. https://doi.org/10.1002/cne.10364
  11. Menet V, Gimenez Y Ribotta M, Sandillon F, Privat A. GFAP null astrocytes are a favorable substrate for neuronal survival and neurite growth. Glia. 2000;31(3):267-72. https://doi.org/10.1002/1098-1136(200009)31:3<267::AID-GLIA80>3.0.CO;2-N
  12. Pekny M, Johansson CB, Eliasson C, Stakeberg J, Wallen A, Perlmann T, Lendahl U, Betsholtz C, Berthold CH, Frisen J.Abnormal reaction to central nervous system injury in mice lacking glial fibrilary acidic protein and vimentin. J Cell Biol. 1999;145:503-14. https://doi.org/10.1083/jcb.145.3.503
  13. 李時珍. 本草綱目. 北京:人民衛生出版社. 1982:699.
  14. 孫星衍. 神農本草經. 臺北:문광도서유한공사. 1979:40-1.
  15. 한정희. 허혈성기억장애 흰쥐모델에서 인삼사포닌이 학습과 기억에 미치는 영향. 동국대학교 석사학위논문. 2005
  16. Zhang G, Liu A, Zhou Y, San X, Jin T, Jin Y. Panax ginseng ginsenoside - Rg2 protects memory impairment via anti - apoptosis in a rat model with vascular dementia. J. Ethnopharmacology. 2008;115:441-8. https://doi.org/10.1016/j.jep.2007.10.026
  17. 김질수. 환경호르몬 PCB 52의 신경세포에 대한 세포 독성기전 및 人蔘의 방어효과, 원광대학교 박사학위 논문. 2001.
  18. Park JK et al. Calcium-independent CaMKII activity is involved in ginsenoside Rb1-mediated neuronal recovery after hypoxic damage. Life Sciences 2005;76:1013-25. https://doi.org/10.1016/j.lfs.2004.10.011
  19. Zhang YG et al. Influences of ginsenosides Rb1 and Rg1 on reversible focal brain ischemia in rats. Acta Pharmacologica Sinica. 1996;17(1):44-8.
  20. 이진구. 중추신경계 손상시 CD81, GFAP 그리고 MAG의 발현에 대한 조구등의 영향. 원광대학교 대학원 박사학위 논문. 2006.
  21. 문성진. 목단피가 손상된 성상신경세포의 CD81 및 GFAP의 발현에 미치는 영향. 원광대학교 대학원 석사학위 논문. 2007.
  22. Zea Longa E, Weinstein PR, Carlson S, Cummins R. Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 1989;20:84-91. https://doi.org/10.1161/01.STR.20.1.84
  23. McKerracher L, David S, Jackson DL, Kottis V, Dunn RJ, Braun PE. Identification of myelin-associated glycoprotein as a major myelin-derived inhibitor of neurite growth. Neuron. 1994;13:805-11. https://doi.org/10.1016/0896-6273(94)90247-X
  24. Ludwin SK, Kosek JC, Eng LF. The topographical distribution of S-100 and GFA proteins in the adu1t rat brain: an immunohistochemica1 study using horseradish peroxidase-labened antibodies. J Comp Neurol. 1976;165(2):197-207. https://doi.org/10.1002/cne.901650206
  25. 김규원, 박정애, 전형오. 성상세포의 새로운 역할. 서울대학교 약학대학, BRIC BioWave. 2004;6(12).
  26. 권오규. 척수 손상 후 운동기능의 회복 및 아교섬유성 산단백질의 변화. 건국대학교 대학원 석사학위 논문. 2003.
  27. Eddelstone M, Mucke L. Molecu1ar profi1es of reactive astrocytes-implication for their role neurologic disease. Neurosci. 1993;54(3):1536.
  28. Fukuyama R, Izumoto T, Fushiki S. The cerebrospinal fluid level of glialfibrillary acidic protein is increased in cerebrospinal fluid from Alzheimer’s disease patients and correlates with severity of dementia. Eur Neurol. 2001;46(1):35-8. https://doi.org/10.1159/000050753
  29. Zhang L, Zhao W, Bing-sheng L, AIkon DL, Barker JL, Chang YH, Wu M, Rubinow DR. TNF-alpha induced over-expression of GFAP is associated with MAPKs. Neuroreport. 2000;11(2):409-12. https://doi.org/10.1097/00001756-200002070-00037
  30. Eng LF, Vanderhaeghen JJ, Bignami A, Gerstl B. An acidic protein isolated from fibrous astrocytes. Brain Res. 1971;28(2):351-4. https://doi.org/10.1016/0006-8993(71)90668-8
  31. Eng LF, Ghirnikar RS, Lee YL. Glial fibrillary acidic protein : FAP - thirty - one - years (1969-2000). Neurochemical Research. 2000;25:1439-51. https://doi.org/10.1023/A:1007677003387
  32. Brook GA, Plate D, Franzen R, Martin D, Moonen G, Schoenen J, Schmitt AB, Noth J, Nacimiento W. Spontaneous longitudinally orientated axonal regeneration is associated with the Schwann cell framework within the lesion site following spinal cord compression injury of the rat. J Neurosci Res. 1998;53:51-65. https://doi.org/10.1002/(SICI)1097-4547(19980701)53:1<51::AID-JNR6>3.0.CO;2-I
  33. Oren R, Takahashi S, Doss C, Levy R, Levy S. TAPA-1, the target of an antiproliferative antibody, defines a new family of transmembrane proteins. Mol Cell Biol. 1990;10:4007-15.
  34. Levy S, Todd SC, Maecker HT. CD81 (TAPA-1): a molecule involved in signal transduction and cell adhesion in the immune system. Annu. Rev. Immunol. 1998;16:89-109. https://doi.org/10.1146/annurev.immunol.16.1.89
  35. Berditchevski F, Tolias KF, Wong K, Carpenter CL, Hemler ME. A novel link between integrins, transmembrane-4 superfamily proteins (CD63 and CD81), and phosphatidylinositol 4-kinase. J Biol Chem. 1997;272(5):2595-8. https://doi.org/10.1074/jbc.272.5.2595
  36. Moon LD, Brecknell JE, Franklin RJM, Dunnett SB, Fawcett JW. Robust regeneration of CNS axons through a track depleted of CNS glia. Exp. Neurol. 2000;161:49-66. https://doi.org/10.1006/exnr.1999.7230
  37. Zhang SX, Geddes JW, Owens JL, Holmberg EG. X-irradiation reduces lesion scarring at the contusion site of adult rat spinal cord. Histol Histopathol. 2005;20(2):519-30.
  38. Bethea JR, Nagashima H, Acosta MC, Briceno C, Gomez F, Marcillo AE, Loor K, Green J, Dietrich WD. Systemically administered interleukin-10 reduces tumor necrosis factor-alpha production and significantly improves functional recovery following traumatic spinal cord injury in rats. J Neurotrauma. 1999;16(10):851-63. https://doi.org/10.1089/neu.1999.16.851
  39. Lee IW. Stem cells and Neurosurgery. J korean neurosurgery Soc. 2003;33:1-12.
  40. Guth L, Albuquerque EX, Deshpande SS, Barrett CP, Donati EJ, Warnick JE. Ineffectiveness of enzyme therapy on regeneration in the transected spinal cord of the rat. J Neurosurg. 1980;52(1):73-86. https://doi.org/10.3171/jns.1980.52.1.0073
  41. Puchala E, Windle WF. The possibility of structural and functional restitution after spinal cord injury. A review. Exp Neurol. 1977;55(1):1-42.
  42. Gimenez Y, Ribotta M, Rajaofetra N, Morin-Richaud C, et al. Oxysterol (7beta-hydroxycholesteryl-3-oleate) promotes serotonergic reinnervation in the lesioned rat spinal cord by reducing glial reaction. J Neurosci Res. 1995;41(1):79-95. https://doi.org/10.1002/jnr.490410110
  43. Brekhman II. Gosudarst lsdat et Med. Lit Leningrad. 1957:118.
  44. 강소신의학원 編, 김창민 外 譯. 중약대사전. 서울:정담. 1998:4481.
  45. 문형철, 김윤욱, 송봉근. 인삼이 중추신경계 손상 동물 모델의 재생에 미치는 영향. 대한침구학회지. 2007;24(6):137-48.
  46. Shieh PC, Taso CW, Li JS, Wu HT, Wen YJ, Kou DH, Cheng JT. Role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the action of ginsenoside Rh2 against beta-amyloid-induced inhibition of rat brain astrocytes. Neuroscience Letters. 2008;434:1-5. https://doi.org/10.1016/j.neulet.2007.12.032
  47. Naval MV, Gomez-Serranillos MP, Carretero ME, Villar AM. Neuroprotective effect of a ginseng(Panax ginseng) root extract on astrocytes primary culture. J. Ethnopharmacology. 2007;112:262-70. https://doi.org/10.1016/j.jep.2007.03.010
  48. 심하나. 단삼이 손상된 뇌신경세포에 미치는 영향. 원광대학교 대학원 석사학위 논문. 2006
  49. 이재원. 도인이 중추신경 재생 촉진에 미치는 영향. 원광대학교 대학원 석사학위 논문. 2006
  50. 이승희. 당귀가 저산소로 손상된 성상세포의 gliosis 억제에 미치는 영향. 원광대학교대학원 석사학위 논문. 2007
  51. Goldberg MA, Dunning SP, Bunn HF. Regulation of the erythropoietin gene : evidence that the oxygen sensor is a heme protein. Science. 1988;242(4884):1412-15. https://doi.org/10.1126/science.2849206
  52. Tomaro ML, Frydman J, Frydman RB. Heme oxygenase induction by $CoCl_{2}$, Co-protoporphyrin IX, phenylhydrazine, and diamide: evidence for oxidative stress involvement. Arch. Biochem. Biophys. 1991:610-17.
  53. Wang G, Hazra TK, Mitra S, Lee HM, Englander EW. Mitochondrial DNA damage and a hypoxic response are induced by $CoCl_{2}$ in rat neuronal PC12 cells. Nucleic Acids Res. 2000;28:2135-40. https://doi.org/10.1093/nar/28.10.2135
  54. Zou W, Zeng J, Zhuo M, Xu W, Sun L, Wang J, Liu X. Involvement of caspase 3 and p38 mitogen activated protein kinase in cobalt chloride induced apoptosis in PC12 cells. J neurosci Res. 2002;28:2135-40.
  55. Pulido MD, Parrish AR. Review Metal-induced apoptosis: mechanisms Mutat Res. Dec. 2003;533(1-2):227-41. https://doi.org/10.1016/j.mrfmmm.2003.07.015
  56. Matsumoto M, Makino Y, Tanaka T, Tanaka H, Ishizaka N, Noiri E, Fujita T, Nangaku M. Induction of renoprotective gene expression by cobalt ameliorates ischemic injury of the kidney in rats. J Am Soc Nephrol. 200314:1825-32. https://doi.org/10.1097/01.ASN.0000074239.22357.06
  57. Park BC, Huh MH, Seo JH. Differential expression of transforming growth factor alpha and insulin like growth factor 2 in chronic active hepatitis B, cirrhosis and hepatocellular carcinoma. J Hepatol. 1995;22:286-94. https://doi.org/10.1016/0168-8278(95)80281-9
  58. Wiesener MS, Maxwell PH. HIF and oxygen sensing; as important to life as the air we breathe. Ann Med. 2003;35:183-90. https://doi.org/10.1080/0785389031000458233
  59. 김인세, 박두진, 권재영, 김해규, 신상욱. 백서의 중대뇌동맥 폐쇄에 의한 허혈성 뇌 손상 모델에서 Dexamethasone과 MK-801이 뇌부종 형성에 미치는 영향. 대한마취과학회지. 1999;37:327-33.
  60. Buchan A, Pulsinelli WA. Hypothermia but not the N-methyl-D-aspartate receptor antagonist, MK-801, attenuates neuronal damage in gerbils subjected to transient global ischemia. J Neurosci. 1990;10(1):311-6.
  61. Petito CK, Feldmann E, Pulsinelli WA, Plum F. Delayed hippocampal damage in humans following cardiorespiratory arrest. Neurology. 1987;37(8):1281-6. https://doi.org/10.1212/WNL.37.8.1281
  62. Johnston M, Mckinney M, Coyle J. Evidence for a cholinergic projection to neocortex form neurons in basal forebrain. Proceedings of the National Academy of Science. 1979;76:5392-6. https://doi.org/10.1073/pnas.76.10.5392
  63. Sutherland RJ, Rodriguez AJ. The role of the fomix/fimbria and some related subcortical structures in place learning and memory. Behavioral Brain Research. 1989;32:265-77. https://doi.org/10.1016/S0166-4328(89)80059-2