TAA로 유발된 간섬유화 동물모델에서 인진청간탕의 효과
Effect of Yinjinchunggan-tang(YJCGT) on Fibrogenesis in Thioacetamide(TAA)-induced Rat Liver Tissue
2
조회
0
다운로드
5
인용
0
참고문헌
키워드
초록
Objective : Yinjinchunggan-tang(YJCGT) is reported previously as having theraputic effects on hepatitis such as anti-implammatory, anti-apoptotic, anti-viral(HBV), etc. Though this prescription is not studied on its anti-fibrogenic effect, it is still expected to have the effect in the liver. Thus, this study was performed to investigate the anti-fibrogenic effect of YJCGT on thioacetamide(TAA)-induced liver fibrosis in rats. Method : Rat liver fibrosis was induced by intraperitoneal TAA injection(150mg/kg) 3 times a week for 5 weeks. After the YJCGT (YJCGT 1g/kg, YJCGT 2g/kg)-treatment, body weight, liver and spleen weights, liver function test, the complete blood count and the portal pressure were studied. In addition, gene expressions of ASMA, procollagen type Ia2, MMP2, TIMP1 and TIMP2, all of which are known to be associated with liver fibrosis, were analyzed by RT-PCR. After YJCGT (YJCGT 1g/kg, YJCGT 2g/kg) treatment, percentages of collagen in TAA-induced rat liver tissue were measured by image analyzer. Results : The body weight of the normal group increased more than that of the control and YJCGT-treated groups. The AST level of the YJCGT 1g/kg-treated group significantly decreased compared to that of the control. The ALT and the GGT levels of the YJCGT 2g/kg-treated group significantly increased compared to those of the control. In the YJCGT-treated groups, WBC, RBC and Hgb elevated by TAA injection decreased but platelet count increased. In the YJCGT 1g/kg-treated group, the portal pressure elevated by TAA injection significantly decreased. The significant decreases in the gene expressions of procollagen type Ia2, MMP2 and TIMP2 were observed in the YJCGT-treated groups. In histological findings, TAA injections caused severe liver fibrosis, but the YJCGT treatment significantly reduced the amounts of hepatic collagens. Conclusions : These results suggest that YJCGT has beneficial effects on the treatment of patients with liver cirrhosis as well as chronic hepatitis. Further study should be done to decide the optimal concentration of the YJCGT for the treatment of liver cirrhosis.
Abstract
Objective : Yinjinchunggan-tang(YJCGT) is reported previously as having theraputic effects on hepatitis such as anti-implammatory, anti-apoptotic, anti-viral(HBV), etc. Though this prescription is not studied on its anti-fibrogenic effect, it is still expected to have the effect in the liver. Thus, this study was performed to investigate the anti-fibrogenic effect of YJCGT on thioacetamide(TAA)-induced liver fibrosis in rats. Method : Rat liver fibrosis was induced by intraperitoneal TAA injection(150mg/kg) 3 times a week for 5 weeks. After the YJCGT (YJCGT 1g/kg, YJCGT 2g/kg)-treatment, body weight, liver and spleen weights, liver function test, the complete blood count and the portal pressure were studied. In addition, gene expressions of ASMA, procollagen type Ia2, MMP2, TIMP1 and TIMP2, all of which are known to be associated with liver fibrosis, were analyzed by RT-PCR. After YJCGT (YJCGT 1g/kg, YJCGT 2g/kg) treatment, percentages of collagen in TAA-induced rat liver tissue were measured by image analyzer. Results : The body weight of the normal group increased more than that of the control and YJCGT-treated groups. The AST level of the YJCGT 1g/kg-treated group significantly decreased compared to that of the control. The ALT and the GGT levels of the YJCGT 2g/kg-treated group significantly increased compared to those of the control. In the YJCGT-treated groups, WBC, RBC and Hgb elevated by TAA injection decreased but platelet count increased. In the YJCGT 1g/kg-treated group, the portal pressure elevated by TAA injection significantly decreased. The significant decreases in the gene expressions of procollagen type Ia2, MMP2 and TIMP2 were observed in the YJCGT-treated groups. In histological findings, TAA injections caused severe liver fibrosis, but the YJCGT treatment significantly reduced the amounts of hepatic collagens. Conclusions : These results suggest that YJCGT has beneficial effects on the treatment of patients with liver cirrhosis as well as chronic hepatitis. Further study should be done to decide the optimal concentration of the YJCGT for the treatment of liver cirrhosis.
참고문헌 (60)
- 통계청, "2007 사망 및 사망원인통계결과"
- Bissel DM, "Hepatic fibrosis and cirrhosis In: Hepatology: A textbook of liver disease", WB Saunders, pp.506~525 (1998)
- Gressner OA, "Biomarkers of liver fibrosis: clinical translation of molecular pathogenesis or based on liver- dependent malfuntion tests", Clin Chim Acta, 381(2), pp.107~113 (2007)
- Friedman SL, "Liver fibrosis-from bench to beside", J Hepatol, pp.s38~s53 (2003)
- liams EJ, "Ralaxin inhibits effective deposition by cultured hepatic stellate cells and decreases rat liver fibrosis in vivo", Gut, 49(4), pp.577~578 (2001)
- Simile MM, "5`-Methylthioadenosine administration prevents lipid peroxidation and fibrogenesis induced in rat liver by carbon- tetrachloride intoxication", J Hepatol, 34, pp.386~394 (2001)
- Yoshiji H, "Imatinib mesylate (STI-571) attenuates liver fibrosis development in rats", Am J Physiol, 228(5), pp.907~913 (2005)
- 경희대학교 부속한방병원, "경희한방처방집", 트윈기획, pp.244~ (1997)
- 우홍정, "만성B형간염에 대한 인진청간탕의 효과", 제2회 한중 학술대회 참가 논문집(간장병), pp.18~53 (1995)
- 강우성, "HCV 환자에서 인진청간탕가미방투여후 Anti-HCV역가의 변화관찰 15예", 전국 한의학 학술대회 논문집, pp.85~86 (1998)
- 김진주, "인진청간탕이 MHV-2로 유발된 마우스의 손상간에 미치는 영향", 경희대학교 대학원 (1996)
- 김영철, "인진청간탕의 안전성에 관한 연구", 경희한의대논문집, 20(1), pp.57~89 (1997)
- 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
- 박용진, "인진청간탕가미방이 간세포의 증식능력에 미치는 영향", 대한한의학회지, 19(1), pp.145~164 (1998)
- 홍상훈, "인진청간탕가미방이 간세포활성세포주기 및 apoptosis에 미치는 영향", 대한한의학회지, 19(2), pp.337~372 (1998)
- 강경태, "인진청간탕가미방이 실험적 흰쥐의 간경변증에 미치는 영향", 경희한의대논문집, 20(2), pp.133~150 (1997)
- 김영철, "인진청간탕이 흰쥐의 간장 비실질세포의 procollagen 합성 억제에 미치는 효과에 관한 연구", 대한한방내과학회지, 24(4), pp.817~825 (2003)
- 박상백, "茵蔯淸肝湯이 DMN 유발 간섬유화와 단백질 발현에 미치는 영향", 대한한방내과학회지, 29(1), pp.200~218 (2008), 대한한방내과학회
- 지형준, "대한약전 및 대한약전외 한약규격주해", 한국메디칼인덱스사, pp.58~700 (1998)
- 김정룡, "소화기계질환", 일조각, pp.662~672 (2005)
- 주광로, "1990년대 후반 한국 성인의 B형 간염 바이러스 표지자 보유양상: 건강검진 수검자 70,347명의 성적조사", 대한소화기학회지, 33, pp.642~652 (1999)
- 권오상, "국내 만성 B형 간염 환자 자녀들의 HBV 감염율의 변화", 대한간학회지, 7(3s), pp.160~162 (2001)
- Gressner AM, "Hepatic fibrogenesis: the puzzel of interacting cells, fibrogenic cytokines, regulatory loops and extracellular matrix molecules", Zeitchrift fur Gastroenterologic, 30s, pp.5~16 (1992)
- Li D, "Liver fibrogenesis and the role of hepatic stellate cells: new insights and prospects for therapy", Journal of Gastroenterology & Hepatology, 14(7), pp.618~633 (1999)
- Niemelȁ O, "Collagen breakdown products as markers of fibrosis and cirrhosis", Alcohol & Alcoholism Supplement, 2, pp.345~352 (1994)
- 이관식, "간섬유화 기전", 대한간학회 제3차 Postgraduate Course, pp.9~19 (2005)
- Friedman SL, "Molecular mechanisms of hepatic fibrosis and principles of therapy", Journal of Gastroenterology, 32(3), pp.424~430 (1997)
- Blouin A, "Distribution of organelles and membranes between hepatocytes and nonhepatocytes in the rat liver parenchyma. A stereological study", J Cell Biol, 72, pp.441~455 (1977)
- Blomhoff R, "Perisinusoidal stellate cells of the liver: important roles in retinol metabolism and fibrosis", FASEB J, 5, pp.271~277 (1991)
- Breitkopf K, "Anti-TGF-beta strategies for the treatment of chronic liver disease", Alcohol Clin Exp Res, 29, pp.121S~131S (2005)
- Rockey DC, "Antifibrotic therapy in chronic liver disease", Clin Gastroenterol Hepatol, 3, pp.95~107 (2005)
- Tangkijvanich P, "Cirrhosis can we reverse hepatic fibrosis?", Eur J Surg Suppl, 587, pp.100~112 (2002)
- Holstege A, "The role of fibrogenesis in the pathogenesis of portal hypertension. In: Holstege A, Hahn EG, Scholmerich J ed. Portal hypertension", Netherland: Kluwer Academic Publishers, pp.33~50 (1955)
- Schuppan D, "Hepatic fibrosis: From bench to bedside", J Gastroenterol Hepatol, 17(s), pp.300~305 (2002)
- Friedman SL, "Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury", J Biol Chem, 275, pp.2247~2250 (2000)
- Bataller R, "Liver fibrosis", J Clin Invest, 115, pp.209~218 (2005)
- Lee KS, "Mechanism of liver fibrosis In: Liver fibrosis", Kunja, pp.27~42 (2000)
- 권영오, "간섬유화 치료의 최신지견", 대한간학회 제3차 Postgraduate Course, pp.33~39 (2005)
- 신상만, "인진이 TGF-β1 유도성 간섬유화에 미치는 영향", 대한한의학회지, 22(3), pp.141~155 (2001)
- 김성아, "茵蔯이 간성상세포의 섬유화 억제에 미치는 영향", 대한한방내과학회지, 29(1), pp.177~188 (2008), 대한한방내과학회
- 강병기, "六鬱湯 및 散鬱湯이 DMN및 담도결찰로 유발된 간경변증에 미치는 영향", 제2회 한중학술대회(간장병)논문집, pp.91~122 (1995), 대한한의사협회
- 이지현, "淸肝解酒湯이 TGF-β1 유도성 간섬유화에 미치는 영향", 대한한방내과학회지, 26(1), pp.1~20 (2005), 대한한방내과학회
- 전재현, "淸肝解酒湯이 알코올 유발 간섬유화와 단백질 발현에 미치는 영향", 대한한방내과학회지, 29(2), pp.469~489 (2008), 대한한방내과학회
- 최은경, "丹蔘이 간성상세포의 섬유화 억제에 미치는 영향", 대한한방내과학회지, 29(2), pp.299~310 (2008), 대한한방내과학회
- Kimura K, "Immunopathogenesis of hepatic fibrosis in chronic liver injury induced by repeatedly administered concanavalin A", Int Immunol, 11, pp.1491~1500 (1999)
- Lee SS, "Hemodynamic characterization of chronic bile duct-ligated rats: effect of pentobarbital sodium", Am J Physiol, 251, pp.G176~G180 (1986)
- Giavarotti L, "Liver necrosis induced by acute intraperitoneal ethanol administration in aged rats", Free Radic Res, 36, pp.269~275 (2002)
- Jeong DH, "Expression patterns of cell cycle-related proteins in a rat cirrhotic model induced by CCl4 or thioacetamide", J Gastroenterol, 36, pp.24~32 (2001)
- Jenkins SA, "A dimethylnitrosamine -induced model of cirrhosis and portal hypertension in the rat", Jouranal of Hepatology, 1, pp.489~499 (1985)
- Xiangnong Li, "Reproducible production of thioacetamide- induced macronodular cirrhosis in the rat with no mortality", Journal of Hepatology, 36, pp.488~493 (2002)
- Muller A, "Thioacetamide-induced cirrhosis-like liver lesions in rats unusefulness and reliability of this animal model", Exp Pathol, 34, pp.229~236 (1988)
- 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)
- Perez Tamayo R, "Is cirrhosis of the liver experimentally produced by CCl4 and adequate model of human cirrhosis?", Hepatology, 3, pp.112~120 (1988)
- 정규원, "만성간질환의 미세구조-간섬유조직증식과 간유동의 성상세포", 대한간학회지, 8(3), pp.343~353 (2002)
- Gianluca Svegliati Baroni, "Interferon -gamma decreases hepatic stellate cell activation and extracellular matrix deposition in rat liver fibrosis", Hepatology, 23(5), pp.1189~1199 (1996)
- Iredale JP, "Mechanisms of spontaneous resolution of rat liver fibrosis. Hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors", J Clin Invest, 102, pp.538~549 (1998)
- Friedman SL, "Reversal of hepatic fibrosis-fact or fantasy?", Hepatology, 43(s), pp.82~88 (2006)
- Friedman SL, "Mechanism and therapy of hepatic fibrosis: report of the AASLD single topic basic research conference", Hepatology, 32, pp.1403~1408 (2000)
- Benyon RC, "Progelatinase A is produced and activated by rat hepatic stellate cells and promotes their proliferation", Hepatology, 30, pp.977~986 (1999)
- Knittel T, "Expression patterns of matrix metalloproteinases and their inhibitors in parenchymal and onoparenchymal cells of rat liver regulation by TNF-alpha and TNF-beta", J Hepatol, 30, pp.48~60 (1999)
