Journal of Acupuncture Research

Korean Acupuncture & Moxibustion Medicine Society (대한침구의학회)
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Anti-inflammatory Effect of Bee Venom Acupuncture at Sinsu($BL_{23}$) in a MPTP Mouse Model of Parkinson Disease

MPTP 유발 파킨슨 병 동물 모델에서의 신수혈($BL_{23}$) 봉독약침의 항염증 효과

  • Kim, Chan-Young (Dept. of Acupuncture & Moxibustion, College of Oriental Medicine, Kyung Hee University) ;
  • Lee, Jae-Dong (Dept. of Acupuncture & Moxibustion, College of Oriental Medicine, Kyung Hee University) ;
  • Lee, Sang-Hoon (Dept. of Acupuncture & Moxibustion, College of Oriental Medicine, Kyung Hee University) ;
  • Koh, Hyung-Kyun (Dept. of Acupuncture & Moxibustion, College of Oriental Medicine, Kyung Hee University)
  • 김찬영 (경희대학교 한의과대학 침구학교실) ;
  • 이재동 (경희대학교 한의과대학 침구학교실) ;
  • 이상훈 (경희대학교 한의과대학 침구학교실) ;
  • 고형균 (경희대학교 한의과대학 침구학교실)
  • Received : 2009.07.07
  • Accepted : 2009.07.28
  • Published : 2009.08.20
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Abstract

목적 : 파킨슨 병은 기저핵 흑질의 치밀부에서 도파민성 신경세포의 퇴행으로 인하여 발생하는 질병으로 신경 염증이 주요 병인으로 밝혀져 있다. 이 연구는 MPTP 유발 파킨슨 병 동물 모델에서 신수혈($BL_{23}$)에 대한 봉독 약침의 항염증 효과 및 그 기전을 확인하기 위해 시행되었다. 방법 : $C57_{BL}$/6쥐를 무처치군, MPTP+saline군, MPTP+BVA(0.06mg/kg)군, MPTP+BVA(0.6mg/kg)군의 4군으로 나눈 뒤 무처치군을 제외한 모든 그룹에 총 8시간 동안 2시간 간격으로 MPTP-HCl(20mg/kg per dose$\times$4)을 복강내로 주입하였다. MPTP+BVA 군에서 봉독약침은 마지막 MPTP 주입 2시간 후부터 48시간 간격으로 신수혈($BL_{23}$)에 양측으로 각 20${\mu}\ell$씩 주입하였고 MPTP+saline군에서는 봉독약침 대신 Saline을 주입하였다. 마지막 MPTP 주입 후 7일째에 쥐의 뇌를 적출한 후 면역조직화학법을 시행하였다. 결과 : MPTP 유발 파킨슨 병 동물 모델에서 신수혈에 대한 봉독약침은 농도 의존적으로 TH-Immunoreactivity neuron의 감소와 microglial activation을 억제하였다. HSP70-IR neuron은 모든 군에서 나타나지 않았다. 결론 : 봉독약침이 용량의존적으로 microglial activation을 억제하는 효과를 통해 도파민성 신경세포의 파괴를 억제함으로써 항염 효과를 나타냄을 알 수 있었다. 이 결과는 봉독약침이 microglial activation 억제를 통해 임상적으로 파킨슨 병과 같은 신경 퇴행성 질병에 있어 유용한 치료수단이 될 수 있음을 시사한다.

Keywords

References

  1. Eric RK, James HS, Thomas MJ. Principles of Neural Science. Fourth edition. International edition. The McGraw-Hill Companies, Inc. 2000 : 862.
  2. Teismann P, Schulz JB. Cellular pathology of Parkinson's disease: astrocytes, microglia and inflammation. Cell Tissue Res. 2004 ; 318(1) : 149-61. https://doi.org/10.1007/s00441-004-0944-0
  3. Aloisi F. Immune function of microglia. Glia. 2001 ; 36(2) : 165-79. https://doi.org/10.1002/glia.1106
  4. Nakajima K, Kohsaka S. Microglia: activation and their significance in the central nervous system. J Biochem. 2001 ; 130(2) : 169-75. https://doi.org/10.1093/oxfordjournals.jbchem.a002969
  5. Kohutnicka M, Lewandowska E, Kurkowska-Jastrzebska I, Czlonkowski A, Czlonkowska A. Microglial and astrocytic involvement in a murine model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Immunopharmacology. 1998 ; 39(3) : 167-80. https://doi.org/10.1016/S0162-3109(98)00022-8
  6. Eiseman JL, von Bredow J, Alvares AP. Effect of honeybee (Apis mellifera) venom on the course of adjuvant-induced arthritis and depression of drug metabolism in the rat. Biochem Pharmacol. 1982 ; 31(6) : 1139-46. https://doi.org/10.1016/0006-2952(82)90354-9
  7. Kwon YB, Lee HJ, Han HJ, Mar WC, Kang SK, Yoon OB, Beitz AJ, Lee JH. The watersoluble fraction of bee venom produces antinociceptive and anti-inflammatory effects on rheumatoid arthritis in rats. Life Sci. 2002 ; 71(2) : 191-204. https://doi.org/10.1016/S0024-3205(02)01617-X
  8. Schmidt JO. Biochemistry of insect venoms. Annu Rev Entomol. 1982 ; 27 : 339-68. https://doi.org/10.1146/annurev.en.27.010182.002011
  9. Lariviere WR, Melzack R. The bee venom test: a new tonic-pain test. Pain. 1996 ; 66(2-3) : 271-7. https://doi.org/10.1016/0304-3959(96)03075-8
  10. Lee JH, Kwon YB, Han HJ, Mar WC, Lee HJ, Yang IS, Beitz AJ, Kang SK. Bee venom pretreatment has both an antinociceptive and anti-inflammatory effect on carrageenan-induced inflammation. J Vet Med Sci. 2001 ; 63(3) : 251-9. https://doi.org/10.1292/jvms.63.251
  11. Castro HJ, Mendez-Lnocencio JI, Omidvar B, Omidvar J, Santilli J, Nielsen HS Jr, Pavot AP, Richert JR, Bellanti JA. A phase I study of the safety of honeybee venom extract as a possible treatment for patients with progressive forms of multiple sclerosis. Allergy Asthma Proc. 2005 ; 26(6) : 470-6.
  12. Mirshafiey A. Venom therapy in multiple sclerosis. Neuropharmacology. 2007 ; 53(3) : 353-61. https://doi.org/10.1016/j.neuropharm.2007.05.002
  13. Han S, Lee K, Yeo J, Kweon H, Woo S, Lee M, Baek H, Kim S, Park K. Effect of honey bee venom on microglial cells nitric oxide and tumor necrosis factor-alpha production stimulated by LPS. J Ethnopharmacol. 2007 ; 111(1) : 176-81. https://doi.org/10.1016/j.jep.2006.11.008
  14. Moon DO, Park SY, Lee KJ, Heo MS, Kim KC, Kim MO, Lee JD, Choi YH, Kim GY. Bee venom and melittin reduce proinflammatory mediators in lipopolysaccharide-stimulated BV2 microglia. Int Immunopharmacol. 2007 ; 7(8) : 1092-101. https://doi.org/10.1016/j.intimp.2007.04.005
  15. Dauer W, Przedborski S. Parkinson's disease: mechanisms and models. Neuron. 2003 ; 39(6) : 889-909. https://doi.org/10.1016/S0896-6273(03)00568-3
  16. Tissieres A, Mitchell HK, Tracy UM. Protein synthesis in salivary glands of Drosophila melanogaster: relation to chromosome puffs. J Mol Biol. 1974 ; 84(3) : 389-98. https://doi.org/10.1016/0022-2836(74)90447-1
  17. Wu C. Heat shock transcription factors: structure and regulation. Annu Rev Cell Dev Biol. 1995 ; 11 : 441-69. https://doi.org/10.1146/annurev.cb.11.110195.002301
  18. Wegele H, Muller L, Buchner J. Hsp70 and Hsp90--a relay team for protein folding. Rev Physiol Biochem Pharmacol. 2004 ; 151 : 1-44. https://doi.org/10.1007/s10254-003-0021-1
  19. Morimoto RI, Santoro MG. Stress-inducible responses and heat shock proteins: new pharmacologic targets for cytoprotection. Nat Biotechnol. 1998 ; 16(9) : 833-8. https://doi.org/10.1038/nbt0998-833
  20. Klucken J, Shin Y, Masliah E, Hyman BT, McLean PJ. Hsp70 Reduces alpha-Synuclein Aggregation and Toxicity. J Biol Chem. 2004 ; 279(24) : 25497-502. https://doi.org/10.1074/jbc.M400255200
  21. Auluck PK, Meulener MC, Bonini NM. Mechanisms of Suppression of {alpha}-Synuclein Neurotoxicity by Geldanamycin in Drosophila. J Biol Chem. 2005 ; 280(4) : 2873-8. https://doi.org/10.1074/jbc.M412106200
  22. Freyaldenhoven TE, Ali SF. Role of heat shock proteins in MPTP-induced neurotoxicity. Ann N Y Acad Sci. 1997 ; 825 : 167-78. https://doi.org/10.1111/j.1749-6632.1997.tb48427.x
  23. Shen HY, He JC, Wang Y, Huang QY, Chen JF. Geldanamycin induces heat shock protein 70 and protects against MPTP-induced dopaminergic neurotoxicity in mice. J Biol Chem. 2005 ; 280(48) : 39962-9. https://doi.org/10.1074/jbc.M505524200
  24. Jackson-Lewis V, Przedborski S. Protocol for the MPTP mouse model of Parkinson's disease. Nat Protoc. 2007 ; 2(1) : 141-51. https://doi.org/10.1038/nprot.2006.342
  25. Yin CS, Jeong HS, Park HJ, Baik YS, Yoon MH, Choi CB, Koh HG. A proposed transpositional acupoint system in a mouse and rat model. Res Vet Sci. 2008 ; 84(2) : 159-65. https://doi.org/10.1016/j.rvsc.2007.04.004
  26. Yoshimoto K, Fukuda F, Hori M, Kato B, Kato H, Hattori H, Tokuda N, Kuriyama K, Yano T, Yasuhara M. Acupuncture stimulates the release of serotonin, but not dopamine, in the rat nucleus accumbens. Tohoku J Exp Med. 2006 ; 208(4) : 321-6. https://doi.org/10.1620/tjem.208.321
  27. Franklin KBJ, Paxinos G. The mouse brain in stereotaxic coordinates. First edition. Sydney : Academic Press. 1996.
  28. Burke RE, Cadet JL, Kent JD, Karanas AL, Jackson-Lewis V. An assessment of the validity of densitometric measures of striatal tyrosine hydroxylase-positive fibers: relationship to apomorphine-induced rotations in 6-hydroxydopamine lesioned rats. J Neurosci Methods. 1990 ; 35(1) : 63-73. https://doi.org/10.1016/0165-0270(90)90095-W
  29. Lawson LJ, Perry VH, Dri P, Gordon S. Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience. 1990 ; 39(1) : 151-70. https://doi.org/10.1016/0306-4522(90)90229-W
  30. Kim WG, Mohney RP, Wilson B, Jeohn GH, Liu B, Hong JS. Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: role of microglia. J Neurosci. 2000 ; 20(16) : 6309-16.
  31. Lang AE, Lozano AM. Parkinson's disease. First of two parts. N Engl J Med. 1998 ; 339(15) : 1044-53. https://doi.org/10.1056/NEJM199810083391506
  32. Deumens R, Blokland A, Prickaerts J. Modeling Parkinson's disease in rats: an evaluation of 6-OHDA lesions of the nigrostriatal pathway. Exp Neurol. 2002 ; 175(2) : 303-17. https://doi.org/10.1006/exnr.2002.7891
  33. Schapira AH. Evidence for mitochondrial dysfunction in Parkinson's disease-a critical appraisal. Mov Disord. 1994 ; 9(2) : 125-38. https://doi.org/10.1002/mds.870090202
  34. Ben-Shachar D, Zuk R, Glinka Y. Dopamine neurotoxicity: inhibition of mitochondrial respiration. J Neurochem. 1995 ; 64(2) : 718-23. https://doi.org/10.1046/j.1471-4159.1995.64020718.x
  35. Hoehn MM, Yahr MD. Parkinsonism: onset, progression, and mortality. Neurology 1998 ; 50(2) : 318-34. https://doi.org/10.1212/WNL.50.2.318
  36. Rosenberg RN. Mitochondrial therapy for Parkinson disease. Arch Neurol. 2002 ; 59(10) : 1523. https://doi.org/10.1001/archneur.59.10.1523
  37. McGeer PL, Yasojima K, McGeer EG. Inflammation in Parkinson's disease. Adv Neurol. 2001 ; 86 : 83-9.
  38. Kim SU, de Vellis J. Microglia in health and disease. J Neurosci Res. 2005 ; 81(3) : 302-13. https://doi.org/10.1002/jnr.20562
  39. Beyer M, Gimsa U, Eyupoglu IY, Hailer NP, Nitsch R. Phagocytosis of neuronal or glial debris by microglial cells: upregulation of MHC class II expression and multinuclear giant cell formation in vitro. Glia. 2000 ; 31(3) : 262-6. https://doi.org/10.1002/1098-1136(200009)31:3<262::AID-GLIA70>3.0.CO;2-2
  40. Langston JW, Forno LS, Tetrud J, Reeves AG, Kaplan JA, Karluk D. Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure. Ann Neurol. 1999 : 46(4) : 598-605. https://doi.org/10.1002/1531-8249(199910)46:4<598::AID-ANA7>3.0.CO;2-F
  41. Kang JM, Park HJ, Choi YG, Choe IH, Park JH, Kim YS, Lim S. Acupuncture inhibits microglial activation and inflammatory events in the MPTP-induced mouse model. Brain Res. 2007 ; 1131(1) : 211-9. https://doi.org/10.1016/j.brainres.2006.10.089
  42. Takumida M, Anniko M. Heat shock protein 70 delays gentamicin-induced vestibular hair cell death. Acta Otolaryngol. 2005 ; 125(1) : 23-8.
  43. Kobayashi K. Induction of heat-shock protein (hsp) by moxibustion. Am J Chin Med. 1995 ; 23(3-4) : 327-30. https://doi.org/10.1142/S0192415X95000390
  44. Sun N, Shi J, Chen L, Liu X, Guan X. Influence of electroacupuncture on the mRNA of heat shock protein 70 and 90 in brain after cerebral ischemia/reperfusion of rats. J Huazhong Univ Sci Technolog Med Sci. 2003 : 23(2) : 112-5. https://doi.org/10.1007/BF02859930
  45. Boyd JD, Jang H, Shepherd KR, Faherty C, Slack S, Jiao Y, Smeyne RJ. Response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) differs in mouse strains and reveals a divergence in JNK signaling and COX-2 induction prior to loss of neurons in the substantia nigra pars compacta. Brain Res. 2007 ; 1175 : 107-16. https://doi.org/10.1016/j.brainres.2007.07.067
  46. Asanuma M, Miyazaki I, Ogawa N. Dopamineor L-DOPA-induced neurotoxicity: the role of dopamine quinone formation and tyrosinase in a model of Parkinson's disease. Neurotox Res. 2003 ; 5(3) : 165-76. https://doi.org/10.1007/BF03033137
  47. Haavik J, Toska K. Tyrosine hydroxylase and Parkinson's disease. Mol Neurobiol. 1998 : 16(3) : 285-309. https://doi.org/10.1007/BF02741387
  48. Hurley FM, Costello DJ, Sullivan AM. Neuroprotective effects of delayed administration of growth/differentiation factor-5 in the partial lesion model of Parkinson's disease. Exp Neurol. 2004. 185(2) : 281-9. https://doi.org/10.1016/j.expneurol.2003.10.003
  49. Oiwa Y, Yoshimura R, Nakai K, Itakura T. Dopaminergic neuroprotection and regeneration by neurturin assessed by using behavioral, biochemical and histochemical measurements in a model of progressive Parkinson's disease. Brain Res. 2002 ; 947(2) : 271-83. https://doi.org/10.1016/S0006-8993(02)02934-7
  50. Park HJ, Lim S, Joo WS, Yin CS, Lee HS, Lee HJ, Seo JC, Leem K, Son YS, Kim YJ, Kim CJ, Kim YS, Chung JH. Acupuncture prevents 6-hydroxydopamine-induced neuronal death in the nigrostriatal dopaminergic system in the rat Parkinson's disease model. Exp Neurol. 2003 ; 180(1) : 93-8. https://doi.org/10.1016/S0014-4886(02)00031-6
  51. Choi SH et al. WHO international standard terminologies on traditional medicine in the western pacific region. First edition. World Health Organization Western Pacific Region. 2007 : 24, 238.
  52. Toriizuka K, Okumura M, Iijima K, Haruyama K, Cyong JC. Acupuncture inhibits the decrease in brain catecholamine contents and the impairment of passive avoidance task in ovariectomized mice. Acupunct Electrother Res. 1999 ; 24(1) : 45-57.