[논문]MPTP 유발 파킨슨병 동물 모델에 대한 봉독약침의 신경보호 효과 및 항염증 효과

박원; 김재규; 김종인; 최도영; 고형균

MPTP 유발 파킨슨병 동물 모델에 대한 봉독약침의 신경보호 효과 및 항염증 효과
Neuroprotective and Anti-inflammatory Effects of Bee Venom Acupuncture on MPTP-induced Mouse 원문보기

大韓鍼灸學會誌= The journal of Korean Acupuncture & Moxibustion Society, v.27 no.3, 2010년, pp.105 - 116

박원 (키즈앤맘 한의원) , 김재규 (부산대학교 한의학전문대학원 침구학교실) , 김종인 (경희대학교 한의과대학 침구학교실) , 최도영 (경희대학교 한의과대학 침구학교실) , 고형균 (경희대학교 한의과대학 침구학교실)

초록
AI-Helper

목적 : 이 연구는 MPTP 유발 파킨슨병 동물 모델에서 봉독약침의 신경보호 효과 및 항염증 효과를 확인하기 위해 시행되었다. 방법 : C57BL/6 mice에 신경독소인 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)를 하루에 2시간 간격으로 MPTP-HCl(20mg/kg per dose)을 4번 복강 내 주입하여 중뇌 흑질의 도파민 신경세포를 파괴한 파킨슨병 동물 모델을 유발하였다. 실험군은 MPTP군, MPTP 현종 BVA군, MPTP 곡지 BVA군, MPTP 신수 BVA군의 4군으로 하였다. 마지막 MPTP 투여 2시간 후에 1차로 봉독약침을 시술하고, 그 후 48시간 간격으로 총 5차 연속 시술하였다. 봉독약침액의 농도는 0.2mg/Kg으로 하였고, 경혈은 양측 현종($GB_{39}$), 곡지($LI_{11}$), 신수($BL_{23}$)를 사용했고, 주입량은 각 경혈당 양측으로 각 $20{\mu\ell}$씩 주입하였다. 항염증작용을 알아보기 위해 TH, MAC-1, iNOS HSP70을, 세포사멸에 대한 신경세포의 보호효과를 알아보기 위해 caspase-3을 면역조직화학법을 사용하여 실시하였다. 결과 : 실험 결과 MPTP 유발 파킨슨병 동물 모델에서 현종 곡지 신수혈에 대한 봉독약침은 TH-Immunoreactivity neuron의 감소와 microglial activation을 억제하였다. 봉독약침군 모두 효과를 보였으나 그 중 현종과 신수혈에서 특히 억제작용이 컸다. MAC-1에서는 현종혈이 억제작용이 컸다. HSP70-IR neuron은 곡지에서 유의한 억제작용을 보였으나, iNOS neuron은 모든 군에서 유의한 차이를 보이지 않았다. 또한 세포사멸억제여부 실험에서 봉독약침은 모두 억제작용을 보였으나 특히 곡지자침군에서 caspase-3 발현을 유의하게 억제하였다. 결론 : 이러한 결과는 봉독약침이 MPTP 투여로 인한 중뇌 흑질의 염증에 의한 도파민 신경세포 손상을, 염증을 억제함으로써 항염 효과를 나타냄을 알 수 있으며, 신경세포를 보호하는 활성이 있음을 보여줌과 동시에 세포사멸을 억제하는 활성이 있다고 사료된다.

주제어

AI 본문요약
AI-Helper

* AI 자동 식별 결과로 적합하지 않은 문장이 있을 수 있으니, 이용에 유의하시기 바랍니다.

제안 방법

Animal experiments were carried out in accordance with the National Institute of Health’s Guide for Care and Use of Laboratory Animals, and experimental procedures were approved by the Institutional Animal Care and Use Committee, Kyung Hee University. At the beginning of the experiment, the animals were randomly divided into four groups: MPTP group, MPTP GB₃₉ BVA group, MPTP LI₁₁ BVA group and MPTP BL₂₃ BVA group. All mice(six per group) received an intraperitoneal(i.
Evaluation of the neuronal staining intensity was performed by measuring the optical density of MAC-1, iNOS, HSP70, and caspase 3-IR neurons in 10 sections from the SNpc.
injection and then resumed at 48 hr intervals for a total of 5 times until the mice were sacrificed, 10 days after the last MPTP injection. For this procedure, the mice in the MPTP+BVA groups were immobilized, and BV was administered into GB₃₉, LI₁₁ and BL₂₃.
Immunohistochemical staining with TH antibody was performed on the brain samples collected from each group 10 days after the last MPTP injection. TH-IR neurons were counted bilaterally at least three TH-immunostained mesencephalicsections.
To determine whether the beneficial effect of BVA was associated with inhibition of the MPTP-induced glial response, we examined the expression of MAC-1, a marker of microglial activation, 10days after the last MPTP injection.

대상 데이터

Six-week-old male C57BL/6 mice(Samtaco Co, Korea), weighing 20～25g, wereusedinallexperiments. Before experiments, the mice were acclimated for 2 weeks in cages at 21°C and were provided with water and food adlibitum.

데이터처리

To rule out a possible change in SNpc volume as an influencing factor, the numbers of TH-IR neuron is expressed as a ratio of controls per area of SNpc. Statistical analysises were performed using analysis of variance (ANOVA). A Bonferroni multiple comparison test was used to compare individual means.

이론/모형

Statistical analysises were performed using analysis of variance (ANOVA). A Bonferroni multiple comparison test was used to compare individual means. Differences between the means of experimental groups were considered significant at p<0.

참고문헌 (58)

Lee JD, Park HJ, Chae Y, Lim S. An Overview of Bee Venom Acupuncture in the Treatment of Arthritis. Evid Based Complement Alternat Med. 2005 ; 2 : 79-84.

상세보기
Goldberg A, Confino-Cohen R. Effectiveness of maintenance bee venom immunotherapy administered at 6-month intervals. Ann Allergy Asthma Immunol. 2007 ; 99 : 352-7.

상세보기
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 : 470-6.

상세보기
Mirshafiey A. Venom therapy in multiple sclerosis. Neuropharmacology. 2007 ; 53(3) : 353-61.

상세보기
Shinto L, Calabrese C, Morris C, Sinsheimer S, Bourdette D. Complementary and alternative medicine in multiple sclerosis: survey of licensed naturopaths. J Altern Complement Med. 2004 ; 10 : 891-7.

상세보기
Wesselius T, Heersema DJ, Mostert JP, Heerings M, Admiraal-Behloul F, Talebian A, Van Buchem MA, De Keyser J. A randomized crossover study of bee sting therapy for multiple sclerosis. Neurology. 2005 ; 65 : 1764-8.

상세보기
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.

상세보기
Kwon YB, Lee HJ, Han HJ, Mar WC, Kang SK, Yoon OB, Beitz AJ, Lee JH. The water-oluble fraction of bee venom produces anti-nociceptive and anti-inflammatory effects on rheumatoid arthritis in rats. Life Sci. 2002 ; 71(2) : 191-204.

상세보기
Schmidt JO. Biochemistry of insect venoms. Annu Rev Entomol. 1982 ; 27 : 339-68.

상세보기
Lariviere WR, Melzack R. The bee venom test: a new tonic-pain test. Pain. 1996 ; 66(2-3) : 271-7.

상세보기
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.

상세보기
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.

상세보기
Dauer W, Przedborski S. Parkinson's disease : mechanisms and models. Neuron. 2003 ; 39 : 889-909.

상세보기
Dehmer T, Lindenau J, Haid S, Dichgans J, Schulz JB, Deficiency of inducible nitric oxide synthase protects against MPTP toxicity in vivo. J Neurochem. 2000 ; 74 : 2213-6.

상세보기
Hunot S, Hirsch EC, Neuroinflammatory processes in Parkinson' disease Ann Neurol. 2003 ; 53 : Suppl 3 S49-58 ; discussion S58-60.
Wilms H, Zecca L, Rosenstiel P, Sievers J, Deuschl G, Lucius R. Inflammation in Parkinson's diseases and other neurodegenerative diseases : cause and therapeutic implications. Curr Pharm Des. 2007 ; 13 : 1925-8.

상세보기
Wu DC, Teismann P, Tieu K, Vila M, Jackson- Lewis V, Ischiropoulos H, Przedborski S. NADPH oxidase mediates oxidative stress in the 1- methyl- 4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease. Proc Natl Acad Sci USA. 2003 ; 100 : 6145-50.

상세보기
Eberhardt O, Schulz JB, Apoptotic mechanisms and antiapoptotic therapy in the MPTP model of Parkinson's disease. Toxicol Lett. 2003 ; 139 : 135-51.

상세보기
Teismann P, Schulz JB. Cellular pathology of Parkinson's disease : astrocytes, microglia and inflammation. Cell Tissue Res. 2004 ; 318(1) : 149-61.

상세보기
Aloisi F. Immune function of microglia. Glia. 2001 ; 36(2) : 165-79.

상세보기
Nakajima K, Kohsaka S. Microglia: activation and their significance in the central nervous system. J Biochem. 2001 ; 130(2) : 169-75.

상세보기
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.

상세보기
McGeer PL, McGeer EG. Glial reactions in Parkinson's disease. Mov Disord. 2008 ; 23 : 474-83.

상세보기
Przedborski S, Vila M. The 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine mouse model : a tool to explore the pathogenesis of Parkinson's disease. Ann N Y Acad Sci. 2003 ; 991 : 189-98.

상세보기
Cassarino DS, Fall CP, Swerdlow RH, Smith TS, Halvorsen EM, Miller SW, Parks JP, Parker WD Jr, Bennett JP Jr. Elevated reactive oxygen species and antioxidant enzyme activities in animal and cellular models of Parkinson's disease. Biochim Biophys Acta. 1997 ; 1362 : 77-86.

상세보기
Teismann P, Vila M, Choi DK, Tieu K, Wu DC, Jackson-Lewis V, Przedborski S, COX-2 and neurodegeneration in Parkinson's disease. Ann NY Acad Sci. 2003 ; 991 : 272-7.

상세보기
Wu C. Heat shock transcription factors: structure and regulation. Annu Rev Cell Dev Biol. 1995 ; 11 : 441-69.

상세보기
Wegele H, Muller L, Buchner J. Hsp70 and Hsp90-a relay team for protein folding. Rev Physiol Biochem Pharmacol. 2004 ; 151 : 1-44.
Morimoto RI, Santoro MG. Stress-inducible responses and heat shock proteins: new pharmacologic targets for cytoprotection. Nat Biotechno.l 1998 ; 16(9) : 833-8.

상세보기
Jackson-Lewis V, Przedborski S. Protocol for the MPTP mouse model of Parkinson's disease. Nat Protoc. 2007 ; 2(1) : 141-51.

상세보기
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.

상세보기
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.

상세보기
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.

상세보기
Freyaldenhoven TE, Ali SF. Role of heat shock proteins in MPTP-induced neurotoxicity. Ann N Y Acad Sci. 1997 ; 825 : 167-78.

상세보기
Tatton NA, Kish SJ, In situ detection of apoptotic nuclei in the substantia nigra compacta of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinetreate d mice using terminal deoxynucleotidyl transferase labelling and acridine orange staining. Neuroscience. 1997 ; 77 : 1037-48.

상세보기
Eberhardt O, Coelln RV, Kugler S, Lindenau J, Rathke-Hartlieb S, Gerhardt E, Haid S, Isenmann S, Gravel C, Srinivasan A, Bahr M, Weller M, Dichgans J, Schulz JB. Protection by synergistic effects of adenovirus-mediated X- chromosomelinked inhibitor of apoptosis and glial cell linederived neurotrophic factor gene transfer in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease. J Neurosci. 2000 ; 20 : 9126-34.

상세보기
Hartmann A, Hunot S, Michel PP, Muriel MP, Vyas S, Faucheux BA, Mouatt-Prigent A, Turmel H, Srinivasan A, Ruberg M, Evan GI, Agid Y, Hirsch EC. Caspase-3 : A vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease. Proc Natl Acad Sci USA. 2000 ; 97 : 2875-80.

상세보기
Lang AE, Lozano AM. Parkinson's disease. First of two parts. N Engl J Med. 1998 ; 339(15) : 1044-53.

상세보기
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.

상세보기
Schapira AH. Evidence for mitochondrial dysfunction in Parkinson's disease-a critical appraisal. Mov Disord. 1994 ; 9(2) : 125-38.
Ben-Shachar D, Zuk R, Glinka Y. Dopamine neurotoxicity : inhibition of mitochondrial respiration. J Neurochem. 1995 ; 64(2) : 718-23.

상세보기
Hoehn MM, Yahr MD. Parkinsonism : onset, progression, and mortality. Neurology. 1998 ; 50(2) : 318-34.

상세보기
Rosenberg RN. Mitochondrial therapy for Parkinson disease. Arch Neurol. 2002 ; 59(10) : 1523.

상세보기
Mc Geer PL, Yasojima K, Mc Geer EG. Inflammation in Parkinson's disease. Adv Neurol. 2001 ; 86 : 83-9.

상세보기
Kim SU, de Vellis J. Microglia in health and disease. J Neurosci Res. 2005 ; 81(3) : 302-13.

상세보기
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.

상세보기
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.

상세보기
Kang JM, Park HJ, Choi YG, Choe IH, Park JH, Kim YS, Lim S. Acupuncture inhibits microglial activation and inflammatory events in the MPTPinduced mouse model. Brain Res. 2007 ; 1131(1) : 211-9.
Tissieres A, Mitchell HK, Tracy UM. Proteinsyn the sis in salivary glands of Drosophila melanogaster: relation to chromosome puffs. J Mol Biol. 1974 ; 84(3) : 389-98.

상세보기
Takumida M, Anniko M. Heat shock protein 70 delays gentamicin-induced vestibular hair cell death. Acta Otolaryngol. 2005 ; 125(1) : 23-8.

상세보기
Kobayashi K. Induction of heat-shock protein(hsp) by moxibustion. Am J Chin Med. 1995 ; 23(3-4) :327-30.
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.

상세보기
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 : 107-116.

상세보기
Asanuma M, MiyazakiI,OgawaN.Dopamine-orLDOPA- induced neurotoxicity : the role of dopamine quinone formationand tyrosinase in a model of Parkinson's disease. Neurotox Res 2003 ; 5(3) : 165-76.

상세보기
Haavik J, Toska K. Tyrosine hydroxylase and Parkinson's disease. Mol Neurobiol. 1998 : 16(3) : 285-309.

상세보기
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.

상세보기
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.

상세보기
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.

상세보기

저자의 다른 논문 :

표제어: PCR

동의어: Packet Collision Rate

용어 설명 출처 목록 (6)

용어 설명: PCR은 세균 특이성이 있는 primer를 이용하여 적은 수의 세균이 있을지라도 쉽게 검출할 수 있는 유용한 방법이며, 이를 이용하여 구강 내 치면세균막이나 타액에서 직접 세균을 검출할 수 있게 되었다[8].

내보내기 구분	파일저장 인쇄 메일전송
구성항목	기본정보 상세정보 관리번호, 논문명, 저널/프로시딩명, 저자 , 발행년, 권, 호, 시작페이지, 끝페이지, 발행기관 관리번호, 논문명, 대등논문명, 저자 , 저널/프로시딩명, 발행기관, 발행년, 발행언어, 권, 호, 시작페이지, 끝페이지, ISBN, ISSN, 주제분야, 키워드, 초록(한글), 초록(영문), 저자(소속기관)
저장형식	Text(ASCII format) Excel format RefWorks Direct Export RIS format (for Reference Manager, ProCite, EndNote), Scholar's Aids, Mendeley
메일정보	받는사람 (필수) @ 보내는사람 (선택) @ 제목 내용 KISTI 검색결과 이메일 서비스
안내	총 건의 자료가 검색되었습니다. 다운받으실 자료의 인덱스를 입력하세요. (1-10,000) 검색결과의 순서대로 최대 10,000건 까지 다운로드가 가능합니다. 데이타가 많을 경우 속도가 느려질 수 있습니다.(최대 2~3분 소요) 다운로드 파일은 UTF-8 형태로 저장됩니다. 파일의 내용이 제대로 보이지 않을실 때는 웹브라우저 상단의 보기 -> 인코딩 -> 자동선택 여부를 확인하십시오. ~ Text(ASCII format) Excel format

연합인증