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

Effects of Rhei Rhizoma on Gastric Ulcer in Sprague-Dawley Rats

대황(大黃)이 흰쥐의 위점막 손상에 미치는 영향

  • Kim, Bum-Hoi (Department of Anatomy, College of Oriental Medicine and Research Institute of Oriental Medicine, Dong-Eui University)
  • 김범회 (동의대학교 한의과대학 해부학교실 & 한의학연구소)
  • Received : 2011.01.19
  • Accepted : 2011.02.14
  • Published : 2011.02.25
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Abstract

Gastric ulcer has multifactorial etiology, and the development of ulcer is known to be caused by gastric acidity, pepsin secretion, gastric motility and gastric mucosal blood flow. The ulcer results from the tissue necrosis and apoptotic cell death triggered by mucosal ischemia, free radical formation and cessation of nutrient delivery. The gastric mucosa is usually exposed to a wide range of aggressive insults, and has developed efficient mechanisms to repair tissue injury. The apoptotic process of gastric mucosa is triggered by the induction of such proapoptotic gene expression, such as BAX. The Bcl-2 family of proteins plays a pivotal role in the regulation of apoptosis. The maintenance of gastric mucosa integrity depends upon the ratio between cell proliferation and cell death. Stress-inducing factors may affect Bcl-2/BAX ratio and thus the rate of apoptosis through modulation of the expression of both proteins depends upon the experimental model. In addition to the regulation of apoptosis, new vessels have to be generated in order to ensure an adequate supply of oxygen and nutrients to the healing gastric mucosa. This events are regulated by several factors. Among them, such polypeptide growth factors, such as vascular endothelial growth factor (VEGF) regulates essential cell functions involved in tissue healing including cell proliferation and differentiation. The purpose of this study was carried to investigate whether Rhei Rhizoma administration might protect apoptotic cell death and promote angiogenesis in gastric mucosa. Sprague-Dawley rats were randomly divided into 4 groups; normal, saline, cimetidine and Rhei Rhizoma-treated group. The saline, cimetidine and Rhei Rhizoma extracts were orally administrated to each group and gastric ulcer was induced by HCl-EtOH solution. After 1 hour, the stomachs were collected for histological observation and immunohistochemistry. In results, Rhei Rhizoma proves to promote to heal wound in gastric ulcer in conclusion and the significant changes of BAX, Bcl-2 and VEGF quantity in gastric mucosa were observed. These results suggest that Rhei Rhizoma extract may promote incision wound healing and has protective effects on gastric ulcer in rats.

Keywords

References

  1. Tulassay, Z., Herszenyi, L. Gastric mucosal defense and cytoprotection. Best Pract Res Clin Gastroenterol. 24(2):99-108, 2010. https://doi.org/10.1016/j.bpg.2010.02.006
  2. Nayeb-Hashemi, H., Kaunitz, J.D. Gastroduodenal mucosal defense. Curr Opin Gastroenterol. 25(6):537-543, 2009. https://doi.org/10.1097/MOG.0b013e328330da7b
  3. 진귀연. 양사수. 실용중서의결합진단치료학. 서울, 일중사, p 437, 1992.
  4. 마귀동. 실용중의비위병학. 상해, 상해중의약대학출판, pp 669-672, 1996.
  5. 김학재, 최준혁, 임상우. 스트레스와 에탄올로 유발된 mouse의 위점막 손상에 대한 귀비탕의 예방효과. 대한한의학회지 24(1):155-168, 2003.
  6. 전국한의과대학 본초학 교수. 본초학. 서울, 영림사, pp 242-243, 1995.
  7. 김도완, 박창국. 전탕시간에 따른 생대황 및 주대황이 어혈병태모형에 미치는 영향. 대한한방내과학회지 19(1):114-133, 1998.
  8. Park, E.K., Choo, M.K., Yoon, H.K., Kim, D.H. Antithrombotic and antiallergic activities of rhaponticin from Rhei Rhizoma are activated by human intestinal bacteria. Arch Pharm Res. 25(4):528-533, 2002. https://doi.org/10.1007/BF02976613
  9. 이영종. 대황 전탕액 분획이 고지사료 투여 흰쥐의 혈중 지질함량에 미치는 영향. 대한본초학회지 15(2):87-93, 2000.
  10. 손영종, 김윤상, 이영종. 대황이 고지혈증 흰쥐의 혈중지질 및 효소활성에 미치는 영향. 대한본초학회지 14(1):61-68, 1999.
  11. 김옥녀. 대황성분과 그 외 약물들의 흰쥐 위궤양 방어작용. 카톨릭대학교논문집. 23: 37-48, 1972.
  12. Tarnawski, A.S. Cellular and molecular mechanisms of gastrointestinal ulcer healing. Dig Dis Sci 50: 24-33, 2005. https://doi.org/10.1007/s10620-005-1272-2
  13. Konturek, P.C., Brzozowski, T., Konturek, S.J., Pajdo, R., Konturek, J.E., Kwiecien S. Apoptosis in gastric mucosa with stress-induced gastric ulcers. J Physiol Pharmacol 50: 211-225, 1999.
  14. Ma, L., Soldato, P.D., Wallace, J.L. Divergent effects of new cyclooxygenase inhibitors on gastric ulcer healing: shifting the angiogenic balance. Proc Nat Acad Sci USA 99: 13243-13247, 2002. https://doi.org/10.1073/pnas.202392199
  15. Szabo, S., Kusstatscher, S., Sakoulas, G., Sandor, Z., Vincze, A., Jadus, M. Growth factors: new 'endogenous drugs' for ulcer healing. Scand J Gastroenterol Suppl 210: 15-18, 1995.
  16. Tarnawski, A.S. Cellular and molecular mechanisms of gastrointestinal ulcer healing. Dig Dis Sci 50: 24-33, 2005. https://doi.org/10.1007/s10620-005-1272-2
  17. Mizui, T., Doteuchi, M. Effect of polyamines on acidified ethanol-induced gastric lesions in rats. Jpn J Pharmacol. 33(5):939-945, 1983. https://doi.org/10.1254/jjp.33.939
  18. Jeong, C.S. Effect of butanol fraction of Panax ginseng head on gastric lesion and ulcer. Arch Pharm Res. 25(1):61-66, 2002. https://doi.org/10.1007/BF02975263
  19. Kurebayashi, Y., Ikeda, T., Osada, Y. Cytoprotective action of cetraxate against HCl.ethanol-induced gastric lesion in rats. Jpn J Pharmacol. 46(1):17-25, 1988. https://doi.org/10.1254/jjp.46.17
  20. Mizui, T., Doteuchi, M. Effect of polyamines on acidified ethanol-induced gastric lesions in rats. Jpn J Pharmacol. 33(5):939-945, 1983. https://doi.org/10.1254/jjp.33.939
  21. Seiki, M., Ueki, S., Tanaka, Y., Soeda, M., Hori, Y., Aita, H., Yoneta, T., Morita, H., Tagashira, E., Okabe, S. Studies on anti-ulcer effects of a new compound, zinc L-carnosine(Z-103). Nippon Yakurigaku Zasshi. 95(5):257-269, 1990. https://doi.org/10.1254/fpj.95.5_257
  22. Ito, M., Shii, D., Segami, T., Kojima, R., Suzuki, Y. Preventive actions of N-(3-aminopropionyl)-L-histidinato zinc (Z-103) through increases in the activities of oxygen-derived free radical scavenging enzymes in the gastric mucosa on ethanol-induced gastric mucosal damage in rats. Jpn J Pharmacol. 59(3):267-274, 1992. https://doi.org/10.1254/jjp.59.267
  23. Itoh, M., Guth, P.H. Role of oxygen-derived free radicals in hemorrhagic shock-induced gastric lesions in the rat. Gastroenterology. 88(5):1162-1167, 1985.
  24. Perry, M.A., Wadhwa, S., Parks, D.A., Pickard, W., Granger, D.N. Role of oxygen radicals in ischemia-induced lesions in the cat stomach. Gastroenterology. 90(2):362-367, 1986.
  25. Yoshikawa, T., Minamiyama, Y., Ichikawa, H., Takahashi, S., Naito, Y., Kondo, M. Role of lipid peroxidation and antioxidants in gastric mucosal injury induced by the hypoxanthine-xanthine oxidase system in rats. Free Radic Biol Med. 23(2):243-250, 1997. https://doi.org/10.1016/S0891-5849(96)00625-9
  26. Maroto, R., Perez-Polo, J.R. BCL-2-related protein expression in apoptosis: oxidative stress versus serum deprivation in PC12 cells. J Neurochem. 69(2):514-523, 1997.
  27. Takahashi, M., Kawabe, T., Ogura, K., Maeda, S., Mikami, Y., Kaneko, N., Terano, A., Omata, M. Expression of vascular endothelial growth factor at the human gastric ulcer margin and in cultured gastric fibroblasts: a new angiogenic factor for gastric ulcer healing. Biochem Biophys Res Commun 234: 493-498, 1997. https://doi.org/10.1006/bbrc.1997.5974
  28. Miyake, T., Suzaki, T., Oishi, M. Correlation of gastric ulcer healing features by endoscopy, stereoscopic microscopy, and histology, and a reclassification of the epithelial regenerative process. Dig Dis Sci. 25(1):8-14, 1980. https://doi.org/10.1007/BF01312726
  29. Tarnawski, A.S. Cellular and molecular mechanisms of gastrointestinal ulcer healing. Dig Dis Sci 50: 24-33, 2005. https://doi.org/10.1007/s10620-005-1272-2
  30. Szabo, S., Vincze, A. Growth factors in ulcer healing: lessons from recent studies. J Physiol Paris 94: 77-81, 2000. https://doi.org/10.1016/S0928-4257(00)00146-7
  31. Berse, B., Brown, L.F., Van de Water L, Dvorak, H.F., Senger, D.R. Vascular permeability factor (vascular endothelial growth factor) gene is expressed differentially in normal tissues, macrophages, and tumors. Mol Biol Cell 3: 211-220, 1992.
  32. Takahashi, M., Kawabe, T., Ogura, K., Maeda, S., Mikami, Y., Kaneko, N., Terano, A., Omata, M. Expression of vascular endothelial growth factor at the human gastric ulcer margin and in cultured gastric fibroblasts: a new angiogenic factor for gastric ulcer healing. Biochem Biophys Res Commun 234: 493-498, 1980.
  33. Takahashi, M., Maeda, S., Ogura, K., Terano, A., Omata, M. The possible role of vascular endothelial growth factor (VEGF) in gastric ulcer healing: effect of sofalcone on VEGF release in vitro. J Clin Gastroenterol 27: 178-182, 1998. https://doi.org/10.1097/00004836-199809000-00020
  34. Suzuki, N., Takahashi, S., Okabe, S. Relationship between vascular endothelial growth factor and angiogenesis in spontaneous and indomethacindelayed healing of acetic acid-induced gastric ulcers in rats. J Physiol Pharmacol 49: 515-527, 1998.
  35. Szabo, S., Vincze, A., Sandor, Z., Jadus, M., Gombos, Z., Pedram, A., Levin, E., Hagar, J., Iaquinto, G. Vascular approach to gastroduodenal ulceration: new studies with endothelins and VEGF. Dig Dis Sci 43(9):40-45, 1998.
  36. Milani, S., Calabro, A. Role of growth factors and their receptors in gastric ulcer healing. Microsc Res Tech. 3(5):360-371, 2001.