Advances in Traditional Medicine

  • 제8권4호
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  • Pages.430-439
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  • 2008
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  • 2662-4052(pISSN)
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  • 2662-4060(eISSN)
경희대학교 융합한의과학연구소 (Kyung Hee Oriental Medicine Research Center)
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Effect of Chungpaesagan-tang on ischemic damage induced by MCAO in spontaneously hypertensive rats

  • Kim, Ko-Eun (Graduate School of East-West Medicine, Kyung Hee University) ;
  • Kim, Soo-Yong (College of Oriental Medicine, Institute of Oriental Medicine, Kyung Hee University) ;
  • Kim, Eun-Young (College of Oriental Medicine, Institute of Oriental Medicine, Kyung Hee University) ;
  • Kim, Bum-Hoi (College of Oriental Medicine, Dong-Eui University) ;
  • Shin, Jung-Won (School of Medicine, Washington University) ;
  • Lee, Hyun-Sam (College of Oriental Medicine, Institute of Oriental Medicine, Kyung Hee University) ;
  • Sohn, Young-Joo (College of Oriental Medicine, Sangji University) ;
  • Jung, Hyuk-Sang (College of Oriental Medicine, Institute of Oriental Medicine, Kyung Hee University) ;
  • Sohn, Nak-Won (Graduate School of East-West Medicine, Kyung Hee University)
  • 발행 : 2008.12.31
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초록

Chungpaesagan-tang (CPSGT) is most frequently used to treat ischemic brain injury in tradition Korean medicine. Clinically, cerebral ischemia is likely to be accompanied by preexisting or complicating disease. However, animal models used to examine the effects of herbal medicines on cerebral ischemia have not given this issue sufficient consideration. The present study was undertaken to determine the effects of CPSGT on focal cerebral ischemia in normal and SHR rats subjected to transient middle cerebral artery occlusion (MCAO). Animals were divided into four groups: Normal (Sprague-Dawley) rats subjected to MACO (the NC+MCAO group), normal rats subjected to MCAO and then administered CPSGT (NC + MCAO + CP), SHR rats subjected to MCAO (SHR + MCAO), and SHR rats subjected to MCAO and then administered CPSGT (SHR + MCAO + CP). MCAO was performed using the intraluminal method. CPSGT was administrated orally twice (1 and 4 h) after MCAO. All animals were sacrificed at 24 h postoperatively. Brain tissues were stained with hematoxylin & eosin, to examine the effect of CPSGT on ischemic brain tissues. In addition, changes in TNF-$\alpha$ expression in ischemic areas were examined by immunostaining. CPSGT was found to significantly reduce infarction areas in normal and SHR rats and infarction volumes in SHR rats. Similarly, CPGST markedly increased neuron numbers and sizes in all treated groups, except cell sizes in SHRs. Furthermore, CPSGT reduced TNF-$\alpha$ expression in MCAO administered SHR rats. The findings of the present study suggest that CPSGT effectively ameliorates neuron damage caused by MACO-induced cerebral ischemia, and that it has a significant neuroprotective effect after cerebral ischemia in SHR.

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참고문헌

  1. Adibhatla RM, Hatcher JF, Sailor K, Dempsey RJ. (2002) Polyamines and central nervous system injury: spermine and spermidine decrease following transient focal cerebral ischemia in spontaneously hypertensive rats. Brain Res. 938, 81-86 https://doi.org/10.1016/S0006-8993(02)02447-2
  2. Aronowski J, Cho KH, Strong R, Grotta JC. (1999) Neurofilament proteolysis after focal ischemia; when do cells die after experimental stroke? J. Cereb. Blood Flow Metab. 19, 652-660 https://doi.org/10.1097/00004647-199906000-00008
  3. Barger SW, Horster D, Furukawa K, Goodman Y, Krieglstein J, Mattson MP. (1995) Tumor necrosis factors alpha and beta protect neurons against amyloid beta-peptide toxicity: evidence for involvement of a kappa B-binding factor and attenuation of peroxide and $Ca^{2+}$ accumulation. Proc. Natl. Acad. Sci. USA. 92, 9328-9332 https://doi.org/10.1073/pnas.92.20.9328
  4. Barone FC, Arvin B, White RF, Miller A, Webb CL, Willette RN, Lysko PG, Feuerstein GZ. (1997) Tumor necrosis factor-alpha. A mediator of focal ischemic brain injury. Stroke 28, 1233-1244
  5. Bartus RT, Dean RL, Cavanaugh K, Eveleth D, Carriero DL, Lynch G. (1995) Time-related neuronal changes following middle cerebral artery occlusion: implications for therapeutic intervention and the role of calpain. J. Cereb. Blood Flow Metab. 15, 969-979
  6. Belayev L, Alonso OF, Busto R, Zhao W, Ginsberg MD. (1996) Middle cerebral artery occlusion in the rat by intraluminal suture. Neurological and pathological evaluation of an improved model. Stroke 27, 1616-1623
  7. Buttini M, Appel K, Sauter A, Gebicke-Haerter PJ, Boddeke HW. (1996) Expression of tumor necrosis factor alpha after focal cerebral ischaemia in the rat. Neuroscience 71, 1-16 https://doi.org/10.1016/0306-4522(95)00414-9
  8. Carswell HV, Anderson NH, Clark JS, Graham D, Jeffs B, Dominiczak AF, Macrae IM. (1999) Genetic and gender influences on sensitivity to focal cerebral ischemia in the stroke-prone spontaneously hypertensive rat. Hypertension 33, 681-685
  9. Coyle P. (1986) Different susceptibilities to cerebral infarction in spontaneously hypertensive (SHR) and normotensive Sprague-Dawley rats. Stroke 17, 520-525
  10. Dawson DA, Ruetzler CA, Hallenbeck JM. (1997) Temporal impairment of microcirculatory perfusion following focal cerebral ischemia in the spontaneously hypertensive rat. Brain Res. 749, 200-208 https://doi.org/10.1016/S0006-8993(96)01166-3
  11. Dawson TM, Snyder SH. (1994) Gases as biological messengers: nitric oxide and carbon monoxide in the brain. J. Neurosci. 14, 5147-5159
  12. Dobrucki LW, Kalinowski L, Uracz W, Malinski T. (2000) The protective role of nitric oxide in the brain ischemia. J. Physiol. Pharmacol. 51, 695-703
  13. Dogan A, Baskaya MK, Rao VL, Rao AM, Dempsey RJ. (1998) Intraluminal suture occlusion of the middle cerebral artery in Spontaneously Hypertensive rats. Neurol. Res. 20, 265-270
  14. Duverger D, MacKenzie ET. (1988) The quantification of cerebral infarction following focal ischemia in the rat: influence of strain, arterial pressure, blood glucose concentration, and age. J. Cereb. Blood Flow Metab. 8, 449-461
  15. Fox G, Gallacher D, Shevde S, Loftus J, Swayne G. (1993) Anatomic variation of the middle cerebral artery in the Sprague-Dawley rat. Stroke 24, 2087-2093
  16. Garcia JH, Liu KF, Ho KL. (1995) Neuronal necrosis after middle cerebral artery occlusion in Wistar rats progresses at different time intervals in the caudoputamen and the cortex. Stroke 26, 636-643
  17. Ginsberg MD, Busto R. (1989) Rodent models of cerebral ischemia. Stroke 20, 1627-1642
  18. Hamada J, Greenberg JH, Croul S, Dawson TM, Reivich M. (1995) Effects of central inhibition of nitric oxide synthase on focal cerebral ischemia in rats. J. Cereb. Blood Flow Metab. 15, 779-786
  19. Harms H, Wiegand F, Megow D, Prass K, Einhaupl KM, Dirnagl U. (2000) Acute treatment of hypertension increases infarct sizes in spontaneously hypertensive rats. Neuroreport. 11, 355-359 https://doi.org/10.1097/00001756-200002070-00027
  20. Heo SY, Kang HS. (1998) Experimental Study on the Effect of Chungpesagantang in Obese Rats. Korean Acad. Orient. Rehabil. Med. 8, 106-126
  21. Hong SK, Kang BJ, Kim YJ, Jo DW, Kang SM. (2000) Protective effect of Chungpesagan-tang against ischemia/reperfusion induced cell injury. Dissertation collect. Korean Inst. of Orient. Med. 5, 111-117
  22. Kim DK, Ryu KW. (1983) Effects of Chungpesagan-Tang on the Liver and Kidney Dysfunction due to Mercuric Chloride Poisoning in Rabbits. Korean Orient. Med. Soc. 4, 3-29
  23. Kim DL, Goh BG, Song IB. (1991) An Experimental Study of the Effect by Chongshimyonjatang and Chongpyesagantang on Immune Response and Anti-Allergic Reaction to Rats and Mice. Dissertation collect. Kyung-Hee Univ. 14, 131-160
  24. Kim JJ, Kim HJ, Ahn BG, Hong WS, Lee SI, Kim WH, Lee HI, Ahn DK, Shin MK. (1978) Studies on the Therapeutics for Liver Diseases in Herb Remedies(II) - Experimental Study on the Effect of Chungpesakan-Tang. Dissertation collect. Kyung-Hee Univ. 1, 9-14
  25. Koo JS, Kim JH. (1997) Effects of Chungpyesagantang on the Diabetic Rats induced by Strep tozotocin. Assoc. Korean Orient. Ped. 11, 227-248
  26. Liu T, Clark RK, McDonnell PC, Young PR, White RF, Barone FC, Feuerstein GZ. (1994) Tumor necrosis factor-alpha expression in ischemic neurons. Stroke 25, 1481-1488
  27. Longa EZ, Weinstein PR, Carlson S, Cummins R. (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20, 84-91
  28. Marks L, Carswell HV, Peters EE, Graham DI, Patterson J, Dominiczak AF, Macrae IM. (2001) Characterization of the microglial response to cerebral ischemia in the stroke-prone spontaneously hypertensive rat. Hypertension 38, 116-122
  29. Meistrell ME, Botchkina GI, Wang H, Di Santo E, Cockroft KM, Bloom O, Vishnubhakat JM, Ghezzi P, Tracey KJ. (1997) Tumor necrosis factor is a brain damaging cytokine in cerebral ischemia. Shock 8, 341-348 https://doi.org/10.1097/00024382-199711000-00005
  30. Nagasawa H, Kogure K. (1989) Correlation between cerebral blood flow and histologic changes in a new rat model of middle cerebral artery occlusion. Stroke 20, 1037-1043
  31. Nakane H, Yao H, Ibayashi S, Kitazono T, Ooboshi H, Uchimura H, Fujishima M. (1998) Protein kinase C modulates ischemia-induced amino acids release in the striatum of hypertensive rats. Brain Res. 782, 290-296 https://doi.org/10.1016/S0006-8993(97)01331-0
  32. Nawashiro H, Martin D, Hallenbeck JM. (1997) Inhibition of tumor necrosis factor and amelioration of brain infarction in mice. J. Cereb. Blood Flow Metab. 17, 229-232 https://doi.org/10.1097/00004647-199702000-00013
  33. Negishi H, Ikeda K, Nara Y, Yamori Y. (2001) Increased hydroxyl radicals in the hippocampus of stroke-prone spontaneously hypertensive rats during transient ischemia and recirculation. Neurosci. Lett. 306, 206-208 https://doi.org/10.1016/S0304-3940(01)01893-6
  34. Niiro M, Simon RP, Kadota K, Asakura T. (1996) Proximal branching patterns of middle cerebral artery (MCA) in rats and their influence on the infarct size produced by MCA occlusion. J. Neurosci. Methods 64, 19-23 https://doi.org/10.1016/0165-0270(95)00058-5
  35. Oh YH, Jung SH, Park IS, Shin KJ, Lee WC. (2001) The Effects of Chungpesagan-Tang Extracts on Reversible Forebrain Ischemia in Sprague-Dawley Rats. Korean Soc. Orient. Intern. Med. 22, 161-174
  36. Song MY, Lee JS, Kim SS, Shin HD. (1998) The clinical study about the effect of Chungpaesagan-Tang and Taeumjowui-Tang on the Taeumin obesity after fasting therapy. Korean Acad. Orient. Rehabil. Med. 8, 34-56
  37. Swanson RA, Morton MT, Tsao-Wu G, Savalos RA, Davidson C, Sharp FR. (1990) A semiautomated method for measuring brain infarct volume. J. Cereb. Blood Flow Metab. 10, 290-293
  38. Winquist RJ, Bohr DF. (1983) Structural and functional changes in cerebral arteries from spontaneously hypertensive rats. Hypertension 5, 292-297
  39. Wolf PA, D'Agostino RB, Belanger AJ, Kannel WB. (1991) Probability of stroke: a risk profile from the Framingham Study. Stroke 22, 312-318
  40. Yang GY, Gong C, Qin Z, Ye W, Mao Y, Bertz AL. (1998) Inhibition of TNFalpha attenuates infarct volume and ICAM-1 expression in ischemic mouse brain. Neuroreport 9, 2131-1234