An Immunohistochemical Study on Effect of Gastrodiae Rhizoma against Neuronal Apoptosis Following Intracerebral Hemorrhage in Rats

천마(天麻)가 뇌실질출혈 흰쥐의 신경세포 자연사에 미치는 영향에 대한 면역조직화학적 연구

  • Song, Sang-Hoon (Dept. of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung-Hee University) ;
  • Lee, Joon-Suk (Dept. of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung-Hee 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)
  • 송상훈 (경희대학교 동서의학대학원 한의과학전공) ;
  • 이준석 (경희대학교 동서의학대학원 한의과학전공) ;
  • 신정원 (경희대학교 동서의학대학원 한의과학전공) ;
  • 김성준 (경희대학교 동서의학대학원 한의과학전공) ;
  • 손낙원 (경희대학교 동서의학대학원 한의과학전공)
  • Received : 2011.08.30
  • Accepted : 2011.10.11
  • Published : 2011.10.30

Abstract

Objectives: This study was carried out in order to examine the effects of Gastrodiae rhizoma(GR) ethanol extract on neuronal apoptosis in intracerebral hemorrhage(ICH)-induced rats. Methods: ICH was induced by the stereotaxic intrastriatal injection of bacterial collagenase type VII in Sprague-Dawley rats. GR was orally given once a day for 3 days after ICH. Histological changes of the peri-hematoma regions were observed by cresyl vioIet staining. Bcl-2-associated X protein(Bax), B-cell blastoma 2(BcI-2) and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) expressions in the affected regions were performed by immunohistochemistry. Results: 1. GR reduced apoptotic bodies and swelling neurons in the peri-hematoma regions of ICH-induced rats. 2. GR significantly reduced TUNEL positive cells in the peri-hematoma regions of ICH-induced rats. 3. GR significantly reduced Bax positive cells in the peri-hematoma regions of ICH-induced rats. 4. GR did not influence Bcl-2 expression in the peri-hematoma regions of ICH-induced rats. Conclusions: These results suggest that GR has neuroprotective effects against ICH-induced apoptosis.

References

  1. 명호진, 이상복, 노재규, 윤병우, 이원용, 권오상. 최근 국내 뇌졸중의 역학적 동향에 대한 연구. 대한신경과학회지. 1989;7:179-87.
  2. 이병철, 유경호. 국내 뇌졸중의 역학. 대한의사협회지. 2002;45:1415-21.
  3. Xi G, Keep RF, Hoff JT. Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol. 2006;5(1):53-63. https://doi.org/10.1016/S1474-4422(05)70283-0
  4. Qureshi AI, Suri MF, Ostrow PT, Kim SH, Ali Z, Shatla AA, Guterman LR, Hopkins LN. Apoptosis as a form of cell death in intracerebral hemorrhage. Neurosurgery. 2003;52(5):1041-7. https://doi.org/10.1227/01.NEU.0000057694.96978.BC
  5. Jenkins A, Mendelow AD, Graham DI, Nath PN, Teasdale GM. Experimental intracerebral hematoma: the role of blood constituents in early ischemia. Br J Neurosurg. 1990;4:45-52. https://doi.org/10.3109/02688699009000681
  6. Lansberg NG, Albers GW, Wijman CA. Symptomatic intracerebral hemorrhage following thrombolytic therapy for acute ischemic stroke: a review of the risk factors. Cerebrovac Dis. 2007;24(1):1-10.
  7. 김호철. 한약약리학. 서울:집문당. 2001:391-3.
  8. 전국한의과대학 본초학교수 공편저. 본조학. 서울:영림사. 1991:504-5.
  9. 안덕균, 육창수. 天麻의 문헌 및 성분연구. 대한한의학회지. 1974;11:56-61.
  10. Yu SJ, Kim JR, Lee CK, Han JE, Lee JH, Kim HS, Hong JH, Kang SG. Gastrodia elata blume and an active component, p-hydroxybenzyl alcohol reduce focal ischemic brain injury through antioxidant related gene expressions. Biol Pharm Bull. 2005;28(6):1016-20. https://doi.org/10.1248/bpb.28.1016
  11. Jung TY, Suh SI, Lee H, Kim IS, Kim HJ, Yon HS, Lee SR. Protective effects of several components of Gastrodia elata on lipid peroxidation in gerbil brain homogenates. Phytother Res. 2007;21(10):960-4. https://doi.org/10.1002/ptr.2193
  12. Kim HJ, Lee SR, Moon KD. Ether fraction of methanol extracts of Gastrodia elata, medicinal herb protects against neuronal cell damage after transient global ischemia in gerbils. Phytother Res. 2003;17(8):909-12. https://doi.org/10.1002/ptr.1246
  13. Kim HJ, Hwang IK, Won MH. Vanillin, 4-hydroxybenzyl aldehyde and 4-hydroxybenzyl alcohol prevent hippocampal CA1 cell death following global ischemia. Brain Res. 2007;1181:130-41. https://doi.org/10.1016/j.brainres.2007.08.066
  14. Hsieh CL, Chen CL, Tang NY, Chuang CM, Hsieh CT, Chiang SY, Lin JG, Hsu SF. Gastrodia elata BL mediates the suppression of nNOS and microglia activation to protect against neuronal damage in kainic acid-treated rats. Am J Chin Med. 2005;33(4):599-611. https://doi.org/10.1142/S0192415X0500320X
  15. Zeng X, Zhang S, Zhang L, Zhang K, Zheng X. A study of the neuroprotective effect of tile phenolic glucoside gastrodin during cerebral ischemia in vivo and in vitro. Planta Med. 2006;72(15):1359-65. https://doi.org/10.1055/s-2006-951709
  16. Lin LC, Chen YF, Tsai TR, Tsai TH. Analysis of brain distribution and biliary excretion of a nutrient supplement, gastrodin, in rat. Anal Chim Acta. 2007;590(2):173-9. https://doi.org/10.1016/j.aca.2007.03.035
  17. Rosenberg GA, Mun-Bryce S, Wesley M, Kornfeld M. Collagenase induced intracerebral hemorrhage in rats. Stroke. 1990;21:801-7. https://doi.org/10.1161/01.STR.21.5.801
  18. Jorgensen HS, Nakayama H, Raaschou HO, Olsen TS. Intracerebral hemorrhage versus infarction: stroke severity, risk factors, and prognosis. Ann Neurol. 1995;38(1):45-50. https://doi.org/10.1002/ana.410380110
  19. Lyden PD, Zivin JA. Hemorrhagic transformation after cerebral ischemia: mechanisms and incidence. Cerebrovasc Brain Metab Rev. 1993;5:1-16.
  20. Kohji Matsushita, Wei Meng, Xiaoying Wang, Minoru Asahi, Kazuko Asahi, Michael A Moskowitz, Eng H Lo. Evidence for apoptosis after intracerebral hemorrhage in rat striatum. J Cereb Blood Flow Metab. 2000;20:396-404. https://doi.org/10.1097/00004647-200002000-00022
  21. Bennett SAL. Tenniswood M, Chen JH, Davidson CM, Keyes MT, Fortin T, Pappas BA. Chronic cerebral hypoperfusion elicits neuronal apoptosis and behavioral impairment. Neuroreport. 1998;9:161-6. https://doi.org/10.1097/00001756-199801050-00033
  22. Bullock R, Brock-Utne J, van Dellen J, Blake G. Intracerebral hemorrhage in a primate model: effect on regional cerebral blood flow. Surg Neurol. 1988;29:101-7. https://doi.org/10.1016/0090-3019(88)90065-1
  23. Nagata S, Golstein P. The Pas death factor. Science. 1995;267:1449-56. https://doi.org/10.1126/science.7533326
  24. 박쾌환, 박동석, 강성길. 天麻수침이 항경련효과에 미치는 영향. 경희한의대논문집. 1988;11:15-35.
  25. 이일돈, 장경전, 송춘호, 안창범. 天麻수침이 진통 및 항경련 효과에 미치는 영향. 대한침구학회지. 1997;14(1):438-48.
  26. 성은진, 김호철, 안덕균. 天麻의 항고혈압 작용에 관한 연구. 대한본초학회지. 1997;12(2):51-62.
  27. 양재하, 권용준, 김미려. 天麻엑기스가 spontaneously hypertensive rat에서 혈압 및 혈장 catecholamin 함량의 변화에 미치는 영향. 대한한의학회지. 1995;16(2):433-46.
  28. Kim HJ, Moon KD, Lee DS, Lee SH. Ethyl ether fraction of Gastrodia elata Blume protects amyloid beta peptide-induced cell death. J Ethnopharmacol. 2003;84(1):95-8. https://doi.org/10.1016/S0378-8741(02)00290-8
  29. Huang NK, Lin YL, Cheng JJ, Lai WL. Gastrodia elata prevents rat pheochromocytoma cells from serum-deprived apoptosis: the role of the MAPK family. Life Sci. 2004;75(13):1649-57. https://doi.org/10.1016/j.lfs.2004.05.008
  30. Xu X, Lu Y, Bie X. Protective effects of gastrodin on hypoxia-induced toxicity in primary cultures of rat cortical neurons. Planta Med. 2007;73(7):650-4. https://doi.org/10.1055/s-2007-981523
  31. Neame SJ, Rubin LL, Philpott KL. Blocking cytochrome c activity within intact neurons inhibits apoptosis. J Cell Biol. 1998;142:1583-93. https://doi.org/10.1083/jcb.142.6.1583
  32. Chan SL, Mattson MP. Caspase and calpain substrates: roles in synaptic plasticity and cell death. J Neurosci Res. 1999;58:167-90. https://doi.org/10.1002/(SICI)1097-4547(19991001)58:1<167::AID-JNR16>3.0.CO;2-K
  33. Charriault-Marlange C, Aggoun-Zouaoui D, Represa A, Ben-Ari Y. Apoptotic features of selective neuronal death in ischemia, epilepsy and gp120 toxicity. Trends Neurosci. 1996;19:109-14. https://doi.org/10.1016/S0166-2236(96)80039-7
  34. Li Y, Powers C, Jiang N, Chopp M. Intact, injured, necrotic and apoptotic cells after focal cerebral ischemia in rat. J Neurol Sci. 1998;156:119-32. https://doi.org/10.1016/S0022-510X(98)00036-7
  35. Gross A, McDonnell JM, Korsmeyer SJ. Bcl-2 family members and the mitochondria in apoptosis. Genes Develop. 1999;13:1899-911. https://doi.org/10.1101/gad.13.15.1899
  36. Krajewski S, Mai JK, Krajewska M, Sikorska M, Mossakowski MJ, Reed JC. Upregulation of Bax protein levels in neurons following cerebral ischemia. J Neurosci 1995;15:6364-76. https://doi.org/10.1523/JNEUROSCI.15-10-06364.1995
  37. Gibson ME, Han BH, Choi J, Knudson CM, Korsmeyer SJ, Parsadanian M, Holtzman DM. BAX contributes to apoptotic-like death following neonatal hypoxia-ischemia: evidence for distinct apoptosis pathways. Mol Med. 2001;7:644-55.
  38. Martinou JC, Dubois-Dauphin M, Staple JK, Rodriguez I, Frankowski H, Missotten M, Albertini P, Talabot D, Catsicas S, Pietra C. Overexpression of Bcl-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia. Neuron. 1994;13(4):1017-30. https://doi.org/10.1016/0896-6273(94)90266-6
  39. Lv L, Liu Y, Shi HF, Dong Q. Qingkailing injection attenuates apoptosis and neurologic deficits in a rat model of intracerebral hemorrhage. J Ethnopharmacol. 2009;125(2):269-73. https://doi.org/10.1016/j.jep.2009.06.031
  40. He ZY, Lu XF, Qu B. Protective effects of shenmai injection on the delayed injury of the cerebral neurons in rat induced by intracerebral hemorrhage. Zhongguo Zhong Yao Za Zhi. 2005;30(7):526-30.