Anti-pathogenetic and Curative Effects of Gyehyeoldeungbokhap-bang (Jixietengfuge-fang) on the Collagen-Induced Arthritis

계혈등복합방(鷄血藤複合方)의 Collagen 유발 관절염 발생 및 치료에 대한 연구

  • Lim, Jin-Seob (Dept. of Oriental Rehabilitation Medicine, College of Oriental Medicine, Se-Myung University) ;
  • Kim, Soon-Joong (Dept. of Oriental Rehabilitation Medicine, College of Oriental Medicine, Se-Myung University)
  • 임진섭 (세명대학교 한의과대학 한방재활의학과교실) ;
  • 김순중 (세명대학교 한의과대학 한방재활의학과교실)
  • Received : 2010.08.18
  • Accepted : 2010.10.06
  • Published : 2010.10.30

Abstract

Objectives : This study was designed to elucidate the anti-pathogenetic and curative effects of Gyehyeoldeungbokhap-bang(Jixietengfuge-fang, GCP) on Type II collagen-induced arthritis(CIA) in mice. Methods : In experiment, twenty four mices were divided into non-treated normal group(n=6), bovine type II collagen-induced control group(n=6), collagen immunized and treated two group medicated with extract of GCP(concentration of extraction: 200 mg/kg n=6, 400 mg/kg n=6) for 4 weeks after collagen immunization, Various experimental such as arthritis, incidence, index, total cell number of spleen, total cell number of peripheral lymph node(PLN), paw joint total cell number, analysis on the percentage of immunofluorescent cells of spleen in CIA induced mice, effects of inflammatory gene expression in spleen, PLN and paw joint of CIA mice, production of cytokine(IFN-${\gamma}$, IL-4, TNF-${\alpha}$, IL-6), analysis of rheumatoid factor(anti-collagen lgG, lgM level in serum) and histopathological study on the paw joint. The arthritis index, incidence were measured a week over 4 weeks after second boosting. Total cell number of spleen, peripheral lymph node, paw joint were measure after performed experiment over 7 weeks. Concentration of cytokine and rheumatoid factor in serum were measured after experiment finished. Histopathological study on the paw joint was measured after 40 days medicated with extract of GCP. Results : 1. Incidence of arthritis and index of arthritis were significantly decreased in treated group with 400 mg/kg. 2. Total cell number of spleen, PLN and paw joint were significantly decreased in treated group. 3. Analysis on the percentage of immunofluorescent cells of spleen in CIA induced mice were significantly controled compare with control group. 4. Effects of inflammatory gene expression in spleen, PLN and paw joint of CIA induced mice were significantly controled compare with control group. 5. IFN-${\gamma}$, IL-6, TNF-${\alpha}$, concentration($pg/m{\ell}$) in serum of treated group was significantly decreased compare with control group. But IL-4 was significantly increased. 6. lgM and lgG concentration($pg/m{\ell}$) in serum of treated group was significantly decreased compare with control group. 7. Histopathologically, suppurative and destructive lesion of synovial membrane, articular cartilage and subchondral bony tissue in treated group were alleviated compare with those of control group. Conclusions : Based on the results described above, it might be consider that Gyehyeoldeungbokhap-bang(Jixietengfuge-fang, GCP) has antiarthritic and analgesic effects and also inhibitory effects on the progression of collagen-induced arthritis mice.

References

  1. 전국의과대학교수 역. 오늘의 진단 및 치료 (Current medical diagnosis & treatment). 서울:도서출판 한우리. 1999:892-9.
  2. 김광혁. 細胞分子免疫學. 서울:정문각. 1998:502-3.
  3. Trentham DE, Townes AS, Kang AH. Autoimmunity to type collagen: An experimental model of arthritis. J. Exp. Med. 1977;146:857-68. https://doi.org/10.1084/jem.146.3.857
  4. Brahn E. Animal models of rheumatoid arthritis. Clues to etiology and treatment. Clinical Orthopaedics & Related Research. 1991;265:42-53.
  5. Bendele A, McComb J, Gould T, McAbee T, Sennello G, Chlipala E, Guy M. Animal models of arthritis: Relevance to human disease. Toxicol Pathol. 1999Jan-Feb;27(1):142-3.
  6. 신병희, 이종수, 신현대. 桂技芍藥知母湯이 제II형 collagen 유발 관절염의 항체에 미치는 영향. 한방물리요법과학회지. 1994;4(1):121-33.
  7. 조수미, 이인선, 최병태. 大防風湯의 콜라겐 유발 흰쥐 관절염 억제 효과에 관한 연구. 한방재활의학회지. 2000;10(2):111-20.
  8. 최정식, 송태원, 김동희. 鷄血藤이 collagen으로 유발된 생쥐의 관절염 억제에 관한 연구. 대한본초학회지. 2003;18(3):79-88.
  9. 구본길, 신혜란, 진광선, 윤일지, 오민석. 神仙氣步湯이 collagen II 유발 관절염의 발생 및 치료에 미치는 영향. 한방재활의학과학회지. 2005;15(4):1-16.
  10. 안덕균. 한국본초도감. 서울:교화사. 1998:119, 312, 534, 570.
  11. 정태호, 김정철, 김문규. 최신면역학 강의. 대구:경북대학교. 1996:25, 211-2, 232-5.
  12. 제이슨 외. 관절염치료법. 서울:집사재. 1997:23-6.
  13. Harris ED Jr. Rheumatoid arthritis: Pathophysiology and implication for therapy. N. Engl. J. Med. 1990;1277-89.
  14. 해리슨 번역편찬위원회. HARRISON'S 내과학. 서울:도서출판정담. 1997:1777-85.
  15. 김노경. 내과학. 서울:고려의학. 1998:877-8, 884.
  16. 대한정형외과학회. 정형외과학. 제 5판. 서울:최신의학사. 2000:57-76, 109-31.
  17. 전국한의과대학 재활의학과교실. 동의재활의학과학. 서울:書苑堂. 1995:95-6, 111-6.
  18. 張伯臾. 中醫內科學. 人民衛生出版. 1988:627.
  19. Steffen C, Timple R. Antigenicity of collagen and it's application in the serological investigation of rheumatoid arthritis area. Int. Arch. allergy. 1963;22:333-49. https://doi.org/10.1159/000229376
  20. Cheung HS, Ryan LM, Kozin F, Mccarty DJ. Identification of collagen subtypes in synovial fluid sediments from arthritis patients. Am. J. Med. 1980;68:73-9. https://doi.org/10.1016/0002-9343(80)90168-0
  21. 오충환, 김순중, 서일복. 가시오가피가 흰쥐의 collagen 유발 관절염의 발생 및 치료에 미치는 영향. 한방재활의학과학회지. 2005;15(3):55-73.
  22. 정수현, 김순중. 三痺湯이 collagen으로 유발된 관절염에 미치는 영향. 한방재활의학회지. 2000;10(1):173-83.
  23. 김성재, 이언정, 김형균, 송봉근. 奏艽가 collagen 유발관절염의 면역반응에 미치는 영향. 대한한의학회지. 1998;19(1):368-84.
  24. 엄재원, 정석희, 이종수, 김성수, 신현대. 骨擔草가 제 II형 collagen 유발 관절염의 항체에 미치는 영향. 한방물리료법과학회지. 1995;5(1):149-61.
  25. 이호근, 정석희, 김성수. 大羌活湯이 제II형 collagen 유발관절염의 항체에 미치는 영향. 한방물리료법과학회지. 1994;4(1):87-99.
  26. 임진섭, 이인선. 大防風湯및 加味大防風湯이 제 II형 Collagen 유발관절염에 미치는 영향. 한방재활의학과학회지. 2001;11(3):125-34.
  27. 김세종. 면역학. 서울:고려의학. 1994:3-8, 148-50.
  28. 박상대. 필수세포생물학. 서울:교보문고. 2004:444-50.
  29. 강재성. 세포분자면역학. 서울:범문사. 2004:3-15.
  30. 한승우, 김신윤, 강영모. 류마티스 관절염에 있어 TGF-${\beta}1$ 유전자 다양성. 대한내과학회지. 2003;65(3):335-6.
  31. 전찬홍, 김진희, 박정호, 안광성, 김형진, 김응호, 안중경, 차훈석, 고은미. 류마티스 관절염 활액내 사이토카인의 농도. 대한내과학회. 2003;64(5):577.
  32. Butler DM, Piccoli DS, Hart PH, Hamilton JA. Stimulation of human synovial fibroblast DNA synthesis by recombinant human cytokines. J. Rheumatol. 1988;15(10):1463-70.
  33. Ahmed ST, Ivashkiv L. Inhibition of IL-6, IL-10 signaling and stat activation by inflammatory and stress pathways. J. Immunol. 2000;165(9):5227-37. https://doi.org/10.4049/jimmunol.165.9.5227
  34. Katherine L, Manson Terry L, Moore James M. Cytokine level in synovial fluid and serum of patient with juvenile rheumatoid arthritis. J. Rheumatol. 1994;21:2359-63.
  35. 金昌種. 病態生理學. 서울:한림상사. 1991:153-77, 664-7.
  36. 김세윤. 류마티스 진료. 서울군자출판사. 2001:219.
  37. Lee DM, Weinblatt ME. Rheumatoid arthritis. Lancet. 2001;358:903-11. https://doi.org/10.1016/S0140-6736(01)06075-5
  38. Van Zeben D, Hazes JM, Zwinderman AH, Cats A, van der Voort EA, Breedveld FC. Clinical significance of rheumatoid factors in early rheumatoid arthritis; results of a follow up study. Ann Rheum Dis. 1992;51(9):1029-35. https://doi.org/10.1136/ard.51.9.1029
  39. Feldmann M, Brennan FM. Rheumatoid arthritis. Cell. 1996;85:307-10. https://doi.org/10.1016/S0092-8674(00)81109-5