동의신경정신과학회지 (Journal of Oriental Neuropsychiatry)

  • 제21권1호
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  • Pages.109-124
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  • 2010
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  • 1226-6396(pISSN)
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  • 2234-4942(eISSN)
대한한방신경정신과학회 (The Korean Society of Oriental Neuropsychiatry)
권호 표지

인삼양영탕(人蔘養榮湯)이 Aβ를 처리한 PC12 세포와 생쥐의 손상 뇌신경조직에 미치는 영향

The Neuroprotective Effects of InSamYangYoung-tang(Renshenyangrongtang) on Aβ-induced Damages in Mice

  • 장영주 (대전대학교 한의과대학 신경정신과교실) ;
  • 정인철 (대전대학교 한의과대학 신경정신과교실) ;
  • 이상룡 (대전대학교 한의과대학 신경정신과교실)
  • Jang, Young-Joo (Dept. of Oriental Neuropsychiatry College of Oriental Medicine, Dae-Jeon University) ;
  • Jung, In-Chul (Dept. of Oriental Neuropsychiatry College of Oriental Medicine, Dae-Jeon University) ;
  • Lee, Sang-Ryong (Dept. of Oriental Neuropsychiatry College of Oriental Medicine, Dae-Jeon University)
  • 투고 : 2010.02.05
  • 심사 : 2010.03.10
  • 발행 : 2010.03.30
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초록

Objectives: This experiment was designed to investigate the effect of the InSamYangYoung-tang(Renshenyangrongtang) extract on $A{\beta}$-induced AD model. Methods: The effects of the InSamYangYoung-tang(Renshenyangrongtang) extract on neural damages of cultured PC12 cells induced by $A{\beta}$ were investigated. The effects of the InSamYangYoung-tang(Renshenyangrongtang) extract on neural damages of hippocampal and cortical neurons in the mouse induced by $\beta$-amyloid were investigated. Results: 1. $A{\beta}$ treatment into neuronal cells activated cell death pathway when analyzed by MTT assay and by histological analysis. Then InSamYangYoung-tang(Renshenyangrongtang) treatment improved cell survival to a similar level as in normal group. 2. $A{\beta}$ treatment increased caspase 3 protein levels but decreased phospho-Erk1/2 in neuronal cells. InSamYangYoung-tang(Renshenyangrongtang) treatment reversed the production levels of two proteins close to those in normal group. 3. $A{\beta}$ treatment induced the atrophy of neuronal cells in terms of neuronal processes and cell body shrinkage, but InSamYangYoung-tang(Renshenyangrongtang) greatly improved their morphology. 4. Neuroprotective activity, as observed in InSamYangYoung-tang(Renshenyangrongtang)-treated groups, was similarly observed in cells treated with galantamine which was used as a positive control. Moreover, overall recovery pattern by InSamYangYoung-tang(Renshenyangrongtang) was similar between cultured PC12 cells and in vivo hippocampal and cerebral cortical neurons in the mouse brain. Conclusions: This experiment shows that the InSamYangYoung-tang(Renshenyangrongtang) may play a protective role in neural tissues damaged by cytotoxic substances. Since neuronal damage seen in degenerative brains such as AD are largely unknown, the current data may provide possible insight into therapeutic strategies for AD treatments. InSamYangYoung-tang(Renshenyangrongtang) might be effective for the treatment of AD. Investigation into the clinical use of the InSamYangYoung-tang(Renshenyangrongtang) for AD is suggested for future research.

키워드

참고문헌

  1. 대한치매학회. 치매 임상적 접근. 서울:아카데미아. 2006:23-4, 30-4, 201, 233-6.
  2. Sisodia SS, Price DL. Role of the ${\beta}$-amyloid protein in Alzheimer's disease. FASEB J. 1995;9(5):366-70.
  3. Haass C, Lemere CA, Capell A, Citronl M, Seubert P, Schenk D, Lannfelt L, Selkoe DJ. The Swedish mutation causes early-onset Alzheimer's disease by ${\beta}$-secretase cleavage within the secretory pathway. Nat Med. 1995;1(12):1291-6. https://doi.org/10.1038/nm1295-1291
  4. Wakabayashi T, Craessaerts K, Bammens L, Bentahir M, Borgions F, Herdewijn P, Staes A, Timmerman E, Vandekerckhove J, Rubinstein E, Boucheix C, Gevaert K, DeStrooper B. Analysis of the gamma-secretase interactome and validation of its association with tetraspanin-enriched microdomains. Nat Cell Biol. 2009;11(11):1340-6. https://doi.org/10.1038/ncb1978
  5. Vassar R, Kovacs DM, Yan R, Wong PC. The ${\beta}$-secretase enzyme BACE in health and Alzheimer's disease: regulation, cellbiology, function, and therapeutic potential. J Neurosci. 2009;29(41):12787-94. https://doi.org/10.1523/JNEUROSCI.3657-09.2009
  6. 孫思邈. 備急千金要方. 서울:행림출판사. 1982:129-35, 534, 545, 550.
  7. 王肯堂. 證治準繩. 서울:정담출판사. 1992:306-7.
  8. 洪元植. 精校黃帝內經素問. 서울:洋醫學硏究院. 1985:37, 124, 196, 217-8, 229.
  9. 張介賓. 張氏景岳全書, 서울:翰成社. 1978:610-1.
  10. 전국한의과대학 신경정신과 교과서편찬위원회. 한의신경정신과학. 경기도:집문당. 2007:236-8, 324-33.
  11. 서정열, 손인철, 금경식. 치매에 대한 東西醫學의 文獻的 考察. 1997;14(1):226-38.
  12. 안탁원, 홍석, 김희철. 腦血管性 치매에 대한 東西醫學的 考察. 한국한의학연구원논문집. 1996;2(1):40-70.
  13. 최용덕, 이광규, 강형원, 유영수. 치매의 病理에 대한 東.西醫學的 考察. 동의생리병리학회지. 1999;13(1):36-46.
  14. 김현수, 이상룡, 정인철. 洗心湯 열수추출물, 초미세분말제형이 Alzheimer's Disease 병태모델에 미치는 영향 동의생리병리학회지. 동의신경정신과학회지. 2007;21(3):688-99.
  15. 임정화, 이상룡. 八味合聰明湯 열수추출물, 초미세분말제형이 Alzheimer's Disease 병태 모텔에 미치는 영향. 동의신경정신과학회지. 2008;19(2):95-110.
  16. 최강욱, 정인철. 천왕보심단 열수추출물, 초미세분말제형이 Alzheimer's disease병태 모델에 미치는 영향. 동의신경정신과학회지. 2008;19(2):77-93.
  17. 김지현 등. 새로운 제형의 치매치료제제의 효능연구. 동의생리병리학회. 2002;16(2):303-10.
  18. 최성열, 김대현, 김상태, 김태헌, 강형원, 류영수. 치매에 대한 최신 실험적 연구 동향(2000년 이후 한의학 학술지를 중심으로). 2008;19(1):125-46.
  19. 陳師文. 太平惠民和劑局方. 臺北:旋風出版社. 1990;165-6.
  20. 龔廷賢. 國譯萬病回春. 서울:癸丑文化社. 1997:371-2.
  21. 하지용, 조성연. 人蔘養榮湯이 抗癌 및 免疫調節作用에 미치는 影響. 대한동의병리학회지. 1998;12(1):60-71.
  22. 은재순, 김대근, 최훈, 오찬호. 人蔘養榮湯이 생쥐의 특이적 면역반응에 미치는 영향. 동의생리병리학회지. 2002;16(4):729-33.
  23. Nam HJ, Kim YB. Effect of Insamyangyoung-tang on the Skin Barrier Function of Hairless Mice. Korean Journal of Oriental Medicine. 2007;28(4):18-26.
  24. Huang S, Lin CM, Chian BH. Protective effects of Angelica sinensis extract on amyloid ${\beta}$-peptide-induced neurotoxicity. Phytomedicine 2008;15;710-21. https://doi.org/10.1016/j.phymed.2008.02.022
  25. 김승현, 이창훈, 이진무, 조정훈, 장준복, 이경섭. 人蔘養營湯의 산화적 stress에 대한 뇌세포 보호효과. 대한한방부인과학회지. 2009;22(1):1-14.
  26. 金甫燮. 人蔘養榮湯加鹿茸과 鹿茸이 Cisplatin으로 誘發된 白鼠의 腎毒性 및 免疫細胞減少에 미치는 影響. 慶熙大學校 大學院. 2001.
  27. 반혜란, 조현정, 정지예, 박경미, 양승정, 조성희. 인삼양영탕 투여로 호전된 갱년기장애 15례에 대한 임상 고찰. 대한한방부인과학회지. 2006;19(3):257-66.
  28. 허준. 동의보감. 경남:동의보감출판사. 2005:170, 554, 1184, 1189, 1261.
  29. Schwab C, McGeer PL. Inflammatory aspects of Alzheimer disease and other neurodegenerative disorders. J Alzheimers Dis. 2008;13(4):359-69. https://doi.org/10.3233/JAD-2008-13402
  30. Hua X, Lei M, Ding J, Han Q, Hu G, Xiao M. Pathological and biochemical alterations of astrocytes in ovariectomized rats injected with D-galactose: a potential contribution to Alzheimer's disease processes. Exp Neurol. 2008;210(2):709-18. https://doi.org/10.1016/j.expneurol.2008.01.009
  31. Dodart JC, May P. Overview on rodent models of Alzheimer's disease. Curr Protoc Neurosci. 2005;9(9):22.
  32. Lannfelt L, Folkesson R, Mohammed AH, Winblad B, Hellgren D, Duff K, Hardy J. Alzheimer's disease: molecular genetics and transgenic animal models. Behav Brain Res. 1993;57(2):207-13. https://doi.org/10.1016/0166-4328(93)90137-F
  33. Duff K. Transgenic models for Alzheimer's disease. Neuropathol Appl Neurobiol. 1998;24(2):101-3. https://doi.org/10.1046/j.1365-2990.1998.00006.x
  34. Volloch V. Possible mechanism for resistance to Alzheimer's disease (AD) in mice suggests a new approach to generate a mouse model for sporadic AD and may explain familial resistance to AD in man. Exp Neurol. 1997;144(1):214-8. https://doi.org/10.1006/exnr.1997.6420
  35. Gandy SE, Buxbaum JD, Suzuki T, Ramabhadran TV, Caporaso GL, Nairn AC, Greengard P. The nature and metabolism of potentially amyloidogenic carboxyl-terminal fragments of the Alzheimer ${\beta}$/A4-amyloid precursor protein: some technical notes. Neurobiol Aging. 1992;13(5):601-3. https://doi.org/10.1016/0197-4580(92)90063-4
  36. Downey D. Pharmacologic management of Alzheimer disease. J Neurosci Nurs. 2008;40(1):55-9. https://doi.org/10.1097/01376517-200802000-00009
  37. Yamin G, Ono K, Inayathullah M, Teplow DB. Amyloid ${\beta}$-protein assembly as a therapeutic target of Alzheimer's disease. Curr Pharm Des. 2008;14(30):3231-46. https://doi.org/10.2174/138161208786404137
  38. Zetterberg H. Update on amyloid-${\beta}$ homeostasis markers for sporadic Alzheimer's disease. Scand J Clin Lab Invest. 2009;69(1):18-21. https://doi.org/10.1080/00365510802651841
  39. Song LL, Du GJ, Fan BY, Zhang DL. Study on pharmacology of ultra-fine particles compound Rehmannia, Zhongguo Zhong Yao Za Zhi. 2002;27(6):436-9.
  40. Simmons ML, Murphy S. Induction of nitric oxide synthase in glial cells. J Neurochem. 1992;59(3):897-905. https://doi.org/10.1111/j.1471-4159.1992.tb08328.x
  41. Tuppo E, Arias H. The role of inflammation in Alzheimer's disease. The International Journal of Biochemistry & Cell Biology. 2005;37(2):289-305. https://doi.org/10.1016/j.biocel.2004.07.009
  42. Suo Z, Tan J, Placzek A, Crawford F, Fang C, Mullan M. Alzheimer's ${\beta}$-amyloid peptides induce inflammatory cascade in human vascular cells: the roles of cytokines and CD40. Brain Research. 1998;807(1-2):110-7. https://doi.org/10.1016/S0006-8993(98)00780-X
  43. 周亞濱, 楊華升. 中藥治療老年性痴呆病近況. 中醫藥學報. 1999;124:73.
  44. 董洪濤,張天嵩. 中醫藥治療老年性痴呆的槪況與分析. 上海中醫藥雜誌. 2000;34(4):17-9.
  45. 王宏獻. 地黃陰子加減治療老年性痴呆50例. 北京中醫. 1998;17(1):13.
  46. 李同新, 劉兆成. 健腦益智合劑治療痴呆96例. 陜西中醫. 2000;21(9):101-2.
  47. 孫景波, 華榮, 曹曉菊. 老年性痴呆病中醫機探討. 陜西中醫. 2000;21(2):71-2.
  48. 韓 旭, 陳美蘭, 胡銑城. 中醫辨證分型治療老年性痴呆病60例. 遼寧中醫雜誌. 1998;25(12):557-8.
  49. 朱俊程. 益氣活血法治療老年期痴呆症54例. 四川中醫. 1999;17(5):30.
  50. 陳 輝. 實用中醫腦病學. 北京,學苑出版社. 1993:793-5.
  51. 黃大東. 實用中醫內科學. 上海:上海科學技術出版社. 1989:378-81
  52. 신재용. 方藥合編解說, 서울:成輔社. 1988:42.
  53. Xia Z, Dickens M, Raingeaud J, Davis RJ, Greenberg ME. Opposing effects of ERK and JNK-p38 MAP kinaseson apoptosis. Science.1995;270(5240):1326-31. https://doi.org/10.1126/science.270.5240.1326
  54. Davis RJ. Signal transduction by the JNK group of MAP kinases. Cell. 2000;103(2):239-52 https://doi.org/10.1016/S0092-8674(00)00116-1
  55. Weston CR, Davis RJ. The JNK signal transduction pathway. Curr Opin Genet Dev. 2002;12(1):14-21. https://doi.org/10.1016/S0959-437X(01)00258-1
  56. Lucas JA. Disorders of memory. Psychiatr Clin North Am. 2005;28(3):581-97, 594. https://doi.org/10.1016/j.psc.2005.05.009
  57. Ohm TG. The dentate gyrus in Alzheimer's disease. Prog Brain Res. 2007;163:723-40. https://doi.org/10.1016/S0079-6123(07)63039-8
  58. Morrison JH, Hof PR. Life and death of neuronsin the aging brain. Science.1997;278(5337):412-9. https://doi.org/10.1126/science.278.5337.412
  59. Laakso MP, Lehtovirta M, Partanen K, Riekkinen PJ, Soininen H. Hippocampus in Alzheimer's disease: a 3-year follow-up MRI study. Biol Psychiatry. 2000;47(6):557-61. https://doi.org/10.1016/S0006-3223(99)00167-5