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인진청간탕 및 와성 어성초 가미방의 간섬유화억제에 미치는 효과

Effect of Yinjinchunggan-tang based Herb Formulae Containing Wasong and Eosungcho on Fibrogenesis

문영훈|우홍정
대한한방내과학회 (The Society Of Korean Oriental Internal Medicine)|2011.06|대한한방내과학회지 (The Journal of Korean Oriental Internal Medicine)|제32권 제2호|pp. 153-169

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키워드

thioacetamideYinjinchunggan-tanghepatic stellate cell
주제분류한의학

초록

Objectives : This study was performed to investigate the anti-fibrogenic effect and the effect on cell growth and apoptosis in YJCGT, YJCGT YSO and YJCGT YSCO on thioacetamide-induced rat liver tissue and the immortalized human hepatic cell line LX2. Materials and Methods : LX2 cells were treated with various concentrations (0, 50, 150, 300 ug/ml) of YJCGT,Y+YSO, and Y+YSCO extract for 24, 48 and 72 hours. After the treatment, cell viability was measured by using MTT assay. Caspase inhibitor assay, and cell viability were determined by a colorimetric assay with PMS/MTS solution. Rat liver fibrosis was induced by intraperitoneal thioacetamide injection 150 mg/kg 3 times a week for 5 weeks. After the treatment, body weight, liver & spleen weights, liver function test, the complete blood cell count and the change of portal pressure were studied. After YJCGT, Y+YSO, and Y+YSCO treatment, percentages of collagen in thioacetamide-induced rat liver tissue were measured. Results : The viability of the LX2 cell decreased in a dose- and time-dependent manner. Exposure of LX2 cells to YJCGT, YJCGT+YSO and YJCGT+YSCO induced caspase-3 activation, but co-treatment of YJCGT, YJCGT+YSO and YJCGT+YSCO with the pan-caspase inhibitor Z-VAD-FMK, and the caspase-3 inhibitor Z-DEVE-FMK, blocked apoptosis. There was no difference in rat body weight between the thioacetamide only group and the YJCGT, YJCGT +YSO and YJCGT+YSCO groups. In the YJCGT, YJCGT YSO and YJCGT YSCO groups, the serum level of GPT significantly went down compared with the thioacetamide only group. In the YJCGT, Y+YSO, Y+YSCO groups, white blood cell elevated by thioacetamide injection decreased but RBC, Hgb, and Hct increased. In the Y+YSO group, the portal pressure elevated by thioacetamide injection significantly decreased. In the histological finding, thioacetamide injections caused severe fibrosis, but YJCGT, Y+YSO, and Y+YSCO treatment significantly reduced the amounts of hepatic collagens. Conclusions : YJCGT, Y+YSO, and Y+YSCO inhibit the growth of LX2 cells by inducing apoptosis through caspase activity. YJCGT, Y+YSO, and Y+YSCO have beneficial effects on the treatment of cirrhotic patients as well as patients with chronic hepatitis.

Abstract

Objectives : This study was performed to investigate the anti-fibrogenic effect and the effect on cell growth and apoptosis in YJCGT, YJCGT YSO and YJCGT YSCO on thioacetamide-induced rat liver tissue and the immortalized human hepatic cell line LX2. Materials and Methods : LX2 cells were treated with various concentrations (0, 50, 150, 300 ug/ml) of YJCGT,Y+YSO, and Y+YSCO extract for 24, 48 and 72 hours. After the treatment, cell viability was measured by using MTT assay. Caspase inhibitor assay, and cell viability were determined by a colorimetric assay with PMS/MTS solution. Rat liver fibrosis was induced by intraperitoneal thioacetamide injection 150 mg/kg 3 times a week for 5 weeks. After the treatment, body weight, liver & spleen weights, liver function test, the complete blood cell count and the change of portal pressure were studied. After YJCGT, Y+YSO, and Y+YSCO treatment, percentages of collagen in thioacetamide-induced rat liver tissue were measured. Results : The viability of the LX2 cell decreased in a dose- and time-dependent manner. Exposure of LX2 cells to YJCGT, YJCGT+YSO and YJCGT+YSCO induced caspase-3 activation, but co-treatment of YJCGT, YJCGT+YSO and YJCGT+YSCO with the pan-caspase inhibitor Z-VAD-FMK, and the caspase-3 inhibitor Z-DEVE-FMK, blocked apoptosis. There was no difference in rat body weight between the thioacetamide only group and the YJCGT, YJCGT +YSO and YJCGT+YSCO groups. In the YJCGT, YJCGT YSO and YJCGT YSCO groups, the serum level of GPT significantly went down compared with the thioacetamide only group. In the YJCGT, Y+YSO, Y+YSCO groups, white blood cell elevated by thioacetamide injection decreased but RBC, Hgb, and Hct increased. In the Y+YSO group, the portal pressure elevated by thioacetamide injection significantly decreased. In the histological finding, thioacetamide injections caused severe fibrosis, but YJCGT, Y+YSO, and Y+YSCO treatment significantly reduced the amounts of hepatic collagens. Conclusions : YJCGT, Y+YSO, and Y+YSCO inhibit the growth of LX2 cells by inducing apoptosis through caspase activity. YJCGT, Y+YSO, and Y+YSCO have beneficial effects on the treatment of cirrhotic patients as well as patients with chronic hepatitis.

참고문헌 (47)

  1. 통계청, "2009 사망원인통계", ~
  2. 이관식, "간섬유화", 대한소화기학회지, 48(5), pp.297~305 (2006), 대한소화기학회
  3. 우홍정, "만성B형간염에 대한 인진청간탕의 효과", 제2회 한중 학술대회 참가 논문집(간장병), pp.18~53 (1995)
  4. 김영철, "인진청간탕의 안전성에 관한 연구", 경희한방대논문집, 20(1), pp.57~89 (1997)
  5. 강경태, "인진청간탕가미방이 실험적 흰쥐의 간경변증에 미치는 영향", 경희한의대논문집, 20(2), pp.133~150 (1997)
  6. 문영훈, "와송이 HepG2 cell의 세포분열 및 관련유전자 발현에 미치는 영향", 대한한방내과학회지, 26(1), pp.48~59 (2005), 대한한방내과학회
  7. 윤경수, "瓦松이 만성 골수성 백혈병 세포주(K562)에서 세포사멸에 미치는 영향", 대한한방내과학회지, 27(1), pp.166~177 (2006), 대한한방내과학회
  8. 안덕균, "원색한국본초도감", pp.69~ (1998), 교학사
  9. 지형준, "대한약전 및 대한약전외 한약규격주해" (1998), 한국메디칼인덱스사
  10. 전국한의과대학 간계내과학 교수, "간계내 과학", pp.323~325 (2001), 동양의학연구원
  11. Friedman SL, "Liver fibrosis-from bench to beside", J Hepatol, 38(1), pp.38~53 (2003)
  12. Williams EJ, "Ralaxin inhibits effective deposition by cultured hepatic stellate cells and decreases rat liver fibrosis in vivo", Gut, 49(4), pp.577~578 (2001)
  13. Yoshiji H, "Imatinib mesylate (STI-571) attenuates liver fibrosis development in rats", Am J Physiol, 288(5), pp.907~913 (2005)
  14. Rockey DC, "Antifibrotic therapy in chronic liver disease", Clin Gastroenterol Hepatol, 3(2), pp.95~107 (2005)
  15. Breitkopf K, "Anti-TGF-beta strategies for the treatment of chronic liver disease", Alcohol Clin Exp Res, 29(11), pp.121~131 (2005)
  16. Tangkijvanich P, "can we reverse hepatic fibrosis", Eur J Surg Suppl, 587, pp.100~112 (2002)
  17. 박경우, "간세포암종 환자에서 병기, 간기능 및 치료법에 따른 3년 생존율 분석", Clinical and Molecular Hepatology, 12(2006), pp.41~54 (2006), 대한간학회
  18. 이관식, "간섬유화 기전", 대한간학회지, 11(2s), pp.9~19 (2006)
  19. Friedman SL, "Molecular mechanisms of hepatic fibrosis and principles of therapy", J Gastroenterol, 32(3), pp.424~430 (1997)
  20. 백용한, "간경변증: 간섬유화 기전 및 항섬유화 치료", 대한간학회지, 14(2s), pp.7~13 (2008)
  21. Breitkopf K, "Anti-TGF -beta strategies for the treatment of chronic liver disease", Alcohol Clin Exp Res, 29(11), pp.121S~131S (2005)
  22. Tangkijvanich P, "can we reverse hepatic fibrosis", Eur J Surg Suppl, 587, pp.100~112 (2002)
  23. 한광협, "간섬유화", 대한간학회지, 16(2s), pp.47~56 (2010)
  24. Friedman SL, "Reversal of hepatic fibrosis---fact or fantasy", Hepatology, 43, pp.82~88 (2006)
  25. An JH, "Rodex signaling by ionizing radiation in mouse liver", Ann N Y Acad Sci, 1030, pp.86~94 (2004)
  26. Exp Pathol, "Thioacetamide -induced cirrhosis-like liver lesions in rats unusefulness and reliability of this animal model", 34(4), pp.229~236 (1988)
  27. Jang KT, "Effect of pehtoxifylline on liver fibrosis and cell cycle related proteins in thioacetamide -induced rat cirrhosis", Korean J Hepatol, 7, pp.281~291 (2001)
  28. Kim KH, "Role of metabolic activation by cytochrome P450 in thioacetamide-induced suppression of antibody response in male BALB", c mice, 2000, pp.114(1), 225~235
  29. Yu Q, "Cell surface-localized matrix metalloproteinase-9 protelytically activates TGF-beta and promotestumor invasion and angiogrnesis", Gene Dev, 14(2), pp.163~176 (2000)
  30. Friedman SL, "Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury", J Biol Chem, 275(4), pp.2247~2250 (2000)
  31. Bataller R, "Liver fibrosis", J Clin Invest, 115(2), pp.209~218 (2005)
  32. Lee KS, "Mechanism of liver fibrosis, In Liver fibrosis", pp.27~42 (2000), Kunja
  33. 권영오, "간섬유화 치료의 최신지견", 대한간학회지, 11(2s), pp.33~39 (2005)
  34. Pinzani M, "Liver fibrosis: from the bench to clinical targets", Dig Liver Lis, 36, pp.231~242 (2004)
  35. 경희대학교 부속한방병원, "경희한방처방집", pp.244~ (1997), 트윈기획
  36. 박용진, "인진청간탕가 미방이 간세포의 증식능력에 미치는 영향", 대한한의학회지, 19(1), pp.145~164 (1998)
  37. 홍상훈, "인진청간탕가미방이 간 세포활성세포주기 및 apoptosis에 미치는 영향", 대한한의학회지, 19(2), pp.337~372 (1998)
  38. 강경태, "茵蔯淸肝湯加味方이 간조직의 섬유화 억제에 미치는 영향", 대한한의학회지, 23(2), pp.227~244 (2002), 대한한의학회
  39. 승현석, "茵蔯淸肝湯이 肝保護 및 纖維化 抑制에 미치는 影響", 대한한방내과학회지, 24(1), pp.21~32 (2003), 대한한방내과학회
  40. 김영철, "인진청간탕이 흰쥐의 간장 비실질세포의 procollagen 합성 억제에 미치는 효과에 관한 연구", 대한한방내과학회지, 24(4), pp.817~825 (2003)
  41. 박상백, "茵蔯淸肝湯이 DMN 유발 간섬유화와 단백질 발현에 미치는 영향", 대한한방내과학회지, 29(1), pp.200~218 (2008), 대한한방내과학회
  42. 박신명, "TAA로 유발된 간섬유화 동물모델에서 인진청간탕의 효과", 대한한방내과학회지, 30(2), pp.270~287 (2009), 대한한방내과학회
  43. 이홍일, "茵蔯清肝汤이 간성상세포의 섬유화 억제에 미치는 영향", 대한한방내과학회지, 30(1), pp.74~84 (2009), 대한한방내과학회
  44. 승현석, "YBR의 肝纖維化 억제 效果에 관한 硏究", 대한한방내과학회지, 31(2), pp.314~330 (2010), 대한한방내과학회
  45. Li X, "Reproducible production of thioacetamide-induced macronodular cirrhosis in the rat with no mortality", J Hepatol, 36(4), pp.488~493 (2002)
  46. Perez Tamayo R, "Is cirrhosis of the liver experimentally produced by CCl4 and adequate model of human cirrhosis", Hepatology, 3(1), pp.112~120 (1988)
  47. Simile MM, "5-Methylthioadenosine administration prevents lipid peroxidation and fibrogenesis induced in rat liver by carbontetrachloride intoxication", J Hepatol, 34(3), pp.386~394 (2001)

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