Journal of Physiology & Pathology in Korean Medicine (동의생리병리학회지)

The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine (대한동의생리학회·한의병리학회)
권호 표지

Neuroprotective Effects of Boyanghwano-tang on Intracerebral Hemorrhage-Induced Rats Using Immunohistochemistry

보양환오탕(補陽還五湯)이 흰쥐 뇌출혈 손상에 미치는 영향에 대한 면역조직화학 연구

  • Cha, Jae-Deog (Division of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Lee, Joon-Suk (Division of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Shin, Jung-Won (Division of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Kim, Seong-Joon (Division of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Kang, Hee (Division of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University) ;
  • Sohn, Nak-Won (Division of Oriental Medical Science, Graduate School of East-West Medical Science, Kyung Hee University)
  • 차재덕 (경희대학교 동서의학대학원 한의과학) ;
  • 이준석 (경희대학교 동서의학대학원 한의과학) ;
  • 신정원 (경희대학교 동서의학대학원 한의과학) ;
  • 김성준 (경희대학교 동서의학대학원 한의과학) ;
  • 강희 (경희대학교 동서의학대학원 한의과학) ;
  • 손낙원 (경희대학교 동서의학대학원 한의과학)
  • Received : 2011.09.02
  • Accepted : 2011.10.06
  • Published : 2011.10.25
Download PDF
⟨ Previous Next ⟩

Abstract

This study was performed in order to evaluate the neuroprotective effect of Boyanghwano-tang (BYT) water extract on intracerebral hemorrhage (ICH). ICH was induced by the stereotaxic intrastriatal injection of bacterial collagenase type IV in Sprague-Dawley rats. BYT was orally given once a day for 3 days after ICH. Hematoma volume and percentage edema were examined. As imflammatory markers, myeloperoxidase (MPO)-positive neutrophils infiltration and iNOS expression in the peri-ICH regions were examined using immunohistochemistry. As cellular damage markers, c-Fos, Bax, and HSP72 positive cells in the peri-ICH regions were measured also. BYT significantly reduced the hematoma volume and percentage edema of the ICH-induced rat brain. In the peri-hematoma regions, BYT significantly reduced MPO-positive neutrophil infiltration and iNOS expression of the ICH-induced rat brain. Additionally, BYT significantly reduced c-Fos, Bax, and HSP72 positive cells in the peri-hematoma regions of the ICH-induced rat brain. These results suggest that BYT plays a neuroprotective role against ICH through suppression of inflammatory responses, apoptosis and cellular damage.

Keywords

References

  1. 王淸任. 醫林改着. 서울, 의성당. pp 84-86, 1994.
  2. 王懁義. 醫林改着發揮. 山西省, 山西科學技術出版社. pp 92-94, 1999.
  3. 정용준, 김동웅. 뇌혈관 질환에 의한 편마비 환자에서 보양환오탕의 효과. 대한동의병리학회지 13(2):54-58, 1999.
  4. 전영수, 김성훈. 보양환오탕과 가미보양환오탕이 Edotoxin으로 유발된 백서의 혈전증에 미치는 영향. 동의병리학회지 8:157-176, 1993.
  5. 김광덕, 송효정. 혈전증 및 고점도혈증에 관한 보양환오탕의 실험적 연구. 대한동의병리학회지 3: 30-46, 1988.
  6. 김남용. 보양환오탕이 혈압 및 국소뇌혈류량에 미치는 영향. 동의생리병리학회지 15(5):682-686, 2001.
  7. 최은정. Mongolian Gerbil의 Reversible forebrain ischemia모델에 미치는 보양환오탕의 효과. 대한한의학회지 43: 88-98, 2000.
  8. 김종길. 보양환오탕이 영양혈청결핍에 의한 PC12 세포의 고사에 미치는 영향. 대한한의학회지 24(2):179-192, 2003.
  9. 이병철, 유경호. 국내 뇌졸중의 역학. 대한의사협회지 45: 1415-1421, 2002.
  10. Ribo, M., Grotta, J.C. Latest advances in intracerebral hemorrhage. Curr Neurol Neurosci Rep. 6(1):17-22, 2006. https://doi.org/10.1007/s11910-996-0004-0
  11. Badjatia, N., Rosand, J. Intracerebral hemorrhage. Neurologist. 11(6):311-324, 2005. https://doi.org/10.1097/01.nrl.0000178757.68551.26
  12. Anderson, K.K., Olsen, T.S., Dehlendorff, C., Kammersgaard, L.P. Hemorrhagic and ischemic strokes compared: Stroke severity, mortality and risk factors. Stroke. 40: 2068-2072, 2009. https://doi.org/10.1161/STROKEAHA.108.540112
  13. Xi, G., Fewel, M.E., Hua, Y., Thompson, B.G. Jr, Hoff, J.T., Keep, R.F. Intracerebral hemorrhage: pathophysiology and therapy. Neurocrit Care. 1(1):5-18, 2004. https://doi.org/10.1385/NCC:1:1:5
  14. Nag, S., Manias, J.L., Stewart, D.J. Pathology and new players in the pathogenesis of brain edema, Acta neuropathol. 118: 197-217, 2009. https://doi.org/10.1007/s00401-009-0541-0
  15. Engelhardt, B., Sorokin, L. The blood-brain and the bloodcerebrospinal fluid barriers: function and dysfunction. Semin Immunopathol. 31: 497-511, 2009. https://doi.org/10.1007/s00281-009-0177-0
  16. Scholz, M., Cinatl, J., Schädel-Höpfner, M., Windolf, J. Neutrophils and the blood-brain barrier dysfunction after trauma. Med Res Rev. 27(3):401-416, 2007. https://doi.org/10.1002/med.20064
  17. Xi, G., Keep, R.F., Hoff, J.T. Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol. 5: 53-63, 2006. https://doi.org/10.1016/S1474-4422(05)70283-0
  18. Schilling, L., Wahl, M. Mediators of cerebral edema. Adv Exp Med Biol. 474: 123-141, 1999.
  19. Rosenberg, G.A., Mun-Bryce, S., Wesley, M., Kornfeld, M. Collagenase induced intracerebral hemorrhage in rats. Stroke. 21: 801-807, 1990. https://doi.org/10.1161/01.STR.21.5.801
  20. 허준. 동의보감. 서울, 남산당, pp 509-519, 1998.
  21. 김영석. 중풍의 병인병리, 변증 및 치료. 한방성인병학회지 1(1):113-140, 1995.
  22. Zazulia, A.R., Diringer, M.N., Derdeyn, C.P., Powers, W.J. Progression of mass effect after intracerebral hemorrhage. Stroke. 30: 1167-1173, 1999. https://doi.org/10.1161/01.STR.30.6.1167
  23. Stanimirovic, D., Satoh, K. Inflammatory mediators of cerebral endothelium: a role in ischemic brain inflammation. Brain Pathol. 10: 113-126, 2000.
  24. Beneviste, E. Inflammatory cytokines within the central nervous systems: Sources, function and mechanism of action. Am J Physiol. 263: 1-16, 1992. https://doi.org/10.1152/ajpcell.1992.263.3.1-a
  25. Allport, J.R., Ding, H., Collins, T., Gerritsen, M.E., Luscinskas, F.W. Endothelial-dependent mechanisms regulate leukocyte transmigration: a process involving the proteasome and disruption of the vascular endothelial-cadherin complex at endothelial cell-to-cell junctions. J Exp Med. 186: 517-627, 1997. https://doi.org/10.1084/jem.186.4.517
  26. Bowes, M.P., Rothlein, R., Fagan, S.C., Zivin, J.A. Monoclonal antibodies preventing leukocyte activation reduce experimental neurologic injury and enhance efficacy of thrombolytic therapy. Neurology. 45: 815-819, 1995. https://doi.org/10.1212/WNL.45.4.815
  27. Yenari, M.A., Kunis, D., Sun, G.H., Onley, D., Watson, L., Turner, S., Whitaker, S., Steinberg, G.K. Hu23F2G, an antibody recognizing the leukocyte CD11/CD18 integrin, reduces injury in a rabbit model of transient focal cerebral ischemia. Exp Neurol. 153: 223-233, 1998. https://doi.org/10.1006/exnr.1998.6876
  28. Koeffler, H.P., Ranyard, J., Pertcheck, M. Myeloperoxidase: its structure and expression during myeloid differentiation. Blood. 65: 484-491, 1985.
  29. Malle, E., Furtmüller, P.G., Sattler, W., Obinger, C. Myeloperoxidase: a target for new drug development? Br J Pharmacol. 152: 838-854, 2007. https://doi.org/10.1038/sj.bjp.0707358
  30. Eiserich, J.P., Hristova, M., Cross, C.E., Jones, A.D., Freeman, B.A., Halliwell, B., van der Vliet A. Formation of nitric oxide-derived inflammatory oxidants by myeloperoxidase in neutrophils. Nature. 391: 393-397, 1998. https://doi.org/10.1038/34923
  31. Sheng, M., Greenberg, M.E. The regulation and function of c-fos and other immediate early genes in the nervous system. Neuron. 4: 477-485, 1990.
  32. Morgan, J.I., Curran, T. Stimulus-transcription coupling in the nervous system: involvement of the inducible proto-oncogenes fos and jun. Annu Rev Neurosci. 14: 421-451, 1991. https://doi.org/10.1146/annurev.ne.14.030191.002225
  33. Akins, P.T., Liu, P.K., Hsu, C.Y. Immediate Early Gene Expression in Response to Cerebral Ischemia; Friend or Foe? Stroke. 27: 1682-1687, 1996. https://doi.org/10.1161/01.STR.27.9.1682
  34. Gross, A., McDonnell, J.M., Korsmeyer, S.J. Bcl-2 family members and the mitochondria in apoptosis. Genes Develop. 13: 1899-1911, 1999. https://doi.org/10.1101/gad.13.15.1899
  35. Krajewski, S., Mai, J.K., Krajewska, M., Sikorska, M., Mossakowski, M.J., Reed, J.C. Upregulation of Bax protein levels in neurons following cerebral ischemia. J Neurosci. 15: 6364-6376, 1995. https://doi.org/10.1523/JNEUROSCI.15-10-06364.1995
  36. Hendrick, J.P., Hartl, F.U. Molecular chaperon functions of heat-shock proteins. Ann. Rev. Biochem. 62: 349-384, 1993. https://doi.org/10.1146/annurev.bi.62.070193.002025
  37. Ma, Y., Hendershot, L.M. The unfolding tale of the unfolded protein response. Cell. 107: 827-830, 2001. https://doi.org/10.1016/S0092-8674(01)00623-7
  38. Welch, W.J. Heat shock proteins functioning as molecular chaperones: their roles in normal and stressed cells. Philos Trans R Soc Lond B Biol Sci. 339: 327-333, 1993. https://doi.org/10.1098/rstb.1993.0031
  39. Kinouchi, H., Sharp, F.R., Koistinaho, J., Hicks, K., Kamii, H., Chan, P.H. Induction of heat shock hsp70 mRNA and HSP70 kDa protein in neurons in the 'penumbra' following focal cerebral ischemia in the rat. Brain Res. 619: 334-338, 1993. https://doi.org/10.1016/0006-8993(93)91630-B