1.行政院衛生署統計室，台灣地區死因統計結果摘要(民國 96 年)，2007。
2. Brenner DA, Waterboer T, Chio SK, Lindquist JN, Stefanovic B, Burchard E, Yamauchi M, Gillan A, Rippe RA. New aspects of hepatic fibrosis. J. Hepatol. 32:
32-38, 2000.
3.Glaser S, Alvaro D, Roskams T, Phinizy JL, Stoica G, Francis H, Ueno Y, Barbaro B, Marzioni M, Mauldin J, Rashid S, Mancino MG, LeSage G, and Alpini G.
Dopaminergic inhibition of secretin-stimulated choleresis by increased PKC-gamma expression and decrease of PKA activity. Am J Physiol Gastrointest Liver Physiol 284: G683-694, 2003.
4.Soderman T，Bronk SF，Robert PJ，Gores GJ.Bile salts mediate hepatocyte apoptosis by increasing call surface trafficking of fas. Am J Physiol
278:G992-G999，2000
5.Gressner AM.Cytokines and celluar crosstalk involved in the activation of fat- storing calls. J Hepatology.22(Suppl.2):28-26,1995
6.Sokol RJ，Devereaux MW.Effect of oxypurinol,a xanthine oxidase inhibitor,on hepatic injury in the bile duct-ligated rat.Pediatr Res.44(3):397-401,1998
7. T. Malmfors and H.Thoenen. 6-Hydroxydopamine and catecholamine neurons.
Clinical Chemistry,18:176-178,1972
84
8.CT Hsu.The role of the sympathetic nervous system in promoting liver cirrhosis induced by carchloride,using the essential hypertensive animal(SHR). J Auton Nerv Syst,37:163-174,1992.
9. Bogert PT, LaRusso NF. Cholangiocyte biology. Curr Opin Gastroenterol.
23:299-305, 2007.
10.Mariano S.H.di FlORE. Atlas of human histology 5th edition.p164-p169,1985.
11. 國家動物中心-實驗動物資訊網 http://las.nhri.org.tw/index1.htm,2008.
12. Alvaro D, Alpini G, Jezequel AM, Bassotti C, Francia C,Fraioli F,Romeo R, Marucci L, LeSage G, Glaser SS, and Benedetti A. Role and mechanisms of action of acetylcholine in the regulation of rat cholangiocyte secretory functions. J Clin Invest 100: 1349–1362, 1997.
13. Jaesschke H, Farhood A, Cai SX, Tseng BY. Protection against TNF- induced liver parenchymal cell apoptosis during endotoxemia by a novel caspase inhibitor in mice. Toxicol Appl Pharmacol 169:77-83, 2000.
14. Boigk G, Stroeter L, Herbst H. Silymarin retards collagen accumulation in early and advance biliary fibrosis secondary to complete bile duct obliteration. Hepatology.
26 (3): 643- 649, 1997.
15.Ramon Bataller,David A Brenner. Liver Fibrosis. J Clin Invest.115:209-218,2005.
85 16.兒茶酚安合成路徑 Catecholamine synthesis.
http://james.pirruccello.us/index.php?title =Image:NESynth.jpg ,2008
17. Bofill-Cardona E, Kudlacek O, Yang Q, Ahorn H, Freissmuth M, and Nanoff C.
Binding of calmodulin to the D2-dopamine receptor reduces receptor signaling by arresting the G protein activation switch. J Biol Chem 275: 32672–32680, 2000.
18. LeSage G, Glaser S, and Alpini G. Regulation of cholangiocyte proliferation. Liver 21: 73-80, 2001.
19. Rodríguez-Garay EA. Cholestasis: human disease and experimental animal models. Ann Hepatol. 2:150-158. 2003.
20. Feranchak AP, Roman RM, Doctor RB, Salter KD, Toker A, and Fitz JG. The lipid products of phosphoinositide 3-kinase contribute to regulation of cholangiocyte ATP and chloride transport. J Biol Chem 274: 30979-30986, 1999.
21. Alvaro D, Mancino MG, Glaser S, Gaudio E, Marzioni M, Francis H, and Alpini G.
Proliferating cholangiocytes: a neuroendocrine compartment in the diseased liver.
Gastroenterology 132: 415-431, 2007.
22. Demorrow S, Francis H, and Alpini G. Biogenic amine actions on cholangiocyte function. Exp Biol Med (Maywood) 232: 1005-1013, 2007.
23. Marzioni M, Fava G, and Benedetti A. Nervous and Neuroendocrine regulation
86
of the pathophysiology of cholestasis and of biliary carcinogenesis. World J Gastroenterol 12: 3471-3480, 2006.
24. Cantley LC. The phosphoinositide 3-kinase pathway. Science;296:1655–1657, 2002.
25.Marzioni M, Francis H, Benedetti A, Ueno Y, Fava G, Venter J,Reichenbach R, Mancino MG, Summers R, Alpini G, Glaser S.Ca2_-dependent cytopro tective effects of ursodeoxycholic andtauroursodeoxycholic acid on the biliary epithelium in a rat model of cholestasis and loss of bile ducts. Am J Pathol 168:398–409,2006.
26. Alpini G,Alvaro D, LeSage G, Marzioni M, LaRusso NF, eds. The patho-
physiology of biliary epithelia. Georgetown, TX: Landes Biosciences 112–122,2004.
27. Gigliozzi A, Alpini G, Baroni GS, Marucci L, Metalli VD, Glaser S,Francis H, Mancino MG, Ueno Y, Barbaro B, Benedetti A, AttiliAF, Alvaro D. Nerve growth factor modulates the proliferativecapacity of the intrahepatic biliary epithelium in experimentalcholestasis.Gastroenterology 127:1198–1209,2004.
28. Alvaro D, Metalli VD, Alpini G, Onori P, Franchitto A, Barbaro B,Glaser S, Francis H, Cantafora A, Blotta I, Attili AF, Gaudio E. Theintrahepatic biliary epithelium is a target of the growth hormone/insulin-like growth factor 1 axis. J Hepatol 43:875–883,2005.
29. Brodie BC. On the effects produced by the bile in the process of digestion. Quart.
87 J. Sci 14,341-346. 1823.
30. Cameron GR, Oakley CL. Ligation of the common bile duct. J Path Bact. 35 769-798. 1932.
31. Wasser S, Tan CE. Experimental models of hepatic fibrosis in the rat. Ann Acad Med Singapore. 28:109-111. 1999.
32. Koeppel TA, Trauner M, Baas JC, Thies JC, Schlosser SF, Post S, Gebhard MM, Herfarth C, Boyer JL, Otto G. Extrahepatic biliary obstruction impairs microvascular perfusion and increases leukocyte adhesion in rat liver. Hepatology. 26:1085-1091.
1997.
33. Alpini G, Glaser S, Alvaro D, Ueno Y, Marzioni M, Francis H,Baiocchi L, Stati T, Barbaro B, Phinizy JL, Mauldin J, LeSage G.Bile acid depletion and repletion
regulate cholangiocyte growthand secretion by a phosphatidylinositol 3-kinase- dependent pathway in rats. Gastroenterology 123:1226–1237,2002.
34. Yerushalmi B, Dahl R, Devereaux MW, Gumpricht E, Sokol RJ. Bile acid-induced rat hepatocyte apoptosis is inhibited by antioxidants and blockers of the mitochondrial permeability transition. Hepatology. 33:616-626. 2001.
35. Kao J. Practical aspects of measuring [Ca2+] with fluorescent indicators. Methods Cell Biol 40: 155–181, 1994.
88
36. Canbay A, Friedman S, Gores GJ. Apoptosis: the nexus of liver injury and fibrosis.
Hepatology. 39:273-278. 2004.
37. Safadi R, Friedman SL. Hepatic fibrosis--role of hepatic stellate cell activation.
Med Gen Med . 4:27. 2002.
38. Reeves HL, Friedman SL. Activation of hepatic stellate cells--a key issue in liver fibrosis. Front Biosci. 7:d808- d826. 2002.
39. Gressner AM, Bachem MG.. Molecular mechanisms of liver fibrogenesis--a homage to the role of activated fat-storing cells. Digestion. 56:335-346. 1995.
40. LeSage EG, Alvaro D, Benedetti A, Glaser S, Marucci L,Baiocchi L, Eisel W, Caligiuri A, Phinizy JL, Rodgers R,Francis H, and Alpini G. Cholinergic system modulates growth, apoptosis, and secretion of cholangiocytes from bile duct-ligated rats. Gastroenterology 117: 191–199, 1999.
41. Nathanson MH, Burgstahler AD, Mennone A, and BoyerJL. Characte rization of cytosolic Ca2_ signaling in rat bile duct epithelia. Am J Physiol Gastrointest Liver Physiol 271: G86–G96, 1996.
42. Ito K, Nakagawa J, Minakuchi C, Fukase M. A clinical evaluation of serum monoamine oxidase, with special reference to hepatic fibrosis. Digestion 4:49-58,1971.
43. Siegel RC, Page RC, Martin GR. The relative activity of connective tissue oxidase
89
and plasma amine oxidase on collagen and elastin substrates. BBA-Molecular Basis Disease 222:552-555,1970.
44. Stefanovic B, Hellerbrand C, Brenner DA. Regulatory role of the conserved stem-loop structure at 5′ end of collagen α1(Ⅰ) . Mol Cell Biochem 19:
4334-4342,1999.
45. Kessler E, Takahara K, Biniaminov L, Brusel M, Greenspan D. Bone morphogenetic protein-1：the type Ⅰprocollagen C-proteinase. Science 271:360-362,1999.
46. Brenner DA, Waterboer T, Choi SK, Lindquist JN, Stefanovic B, Burchardt E, Yamauchi M, Gillan A, Rippe RA. New aspects of hepatic fibrosis. Hepatology 32:32-38, 2000.
47. 0gawa K, Suzuki J I, Mukai H. Sequential changes of extracellular matrix and proliferation of Ito cells with enhanced expression of desmin and actin in focal hepatic injury. Am J Pathol 125:611-619, 1986.
48. Niki T, Pekny M, Hellemans K, Bleser P, Berg K, Vaeyens F . Class Ⅵ
intermediate filament protein nestin is induced during activation of rat hepatic stellate cells. Hepatology 29:520-527,1999.
49. Friedman SL. Mechanisms of Disease: mechanisms of hepatic fibrosis and therapeutic implications. Nature Clinical Practice Gastroenterology & Hepatology
90 1:98-105,2004.
50. Friedman SL. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J. Biol. Chem. 275: 2247-2250 ,2000.
51. Friedman SL, Maher JJ, Bissell DM. Mechanisms and therapy of hepatic fibrosis:
report of the AASLD Single Topic Basic Research Conference. Hepatology 32:1403-1408 ,2000.
52. Nowicki S, Kruse MS, Brismar H, and Aperia A. Dopamine induced translocation of protein kinase C isoforms visualized in renal epithelial cells. Am J Physiol Cell Physiol 279: C1812–C1818, 2000.
53. Elke M B, Wolfgang H, Stephan K, Christine W, Büschenfelde MZ, Hermann K, Hans PD, Ansgar WL. Transforming growth factor-β1 in autoimmune hepatitis:
correlation of liver tissue expression and serum levels with disease activity.
Hepatology 28:803-811 ,1998.
54. Bedossa P, Peltier E, Terris B, Franco D, Poynard T. Transforming growth factor - beta 1 (TGF- 1) and TGF- 1 receptors in normal, cirrhotic, and neoplastic human livers. Hepatology 21: 760-766 ,1995.
55. Yau MH, Che CT, Liang SM, Kong YC, Fong WP. An aqueous extract of Rubus chingii fruits protects primary rat hepatocytes against tert-butyl hydroperoxide induced oxidative stress. Life Sciences 72:329-338 ,2002.
91
56. Taniguchi K, Umeshita K, Sakon M, Miyoshi H, Tokunaga M, Ariyoshi H,
Yamano T, Kaneda Y, Monden M. Suppression of oxidative stress-induced hepatocyte injury by calpain antisense. The Journal of Surgical Research 111:23-27 ,2003.
57. Sumbayev W, Sandau KB, Brune B. Mesangial cells but not hepatocytes are protected against NO/O2- cogeneration: mechanistic considerations.Eur J Pharmacol 444:1-11 ,2002.
58. Whalen R, Rockey DC, Friedman SL, Boyer TD. Activation of rat hepatic stellate cells leads to loss of glutathione S- transferases and their enzymatic activity against products of oxidative stress. Hepatology 30:927-933 ,1999.
59. Svegliati-Baroni G, Saccomanno S, van Goor H, Jansen P, Benedetti A, Moshage H. Involvement of reactive oxygen species and nitric oxide radicals in activation and proliferation of rat hepatic stellate cells. Liver 21:1-12 ,2001.
60. Senogles SE. The D2s dopamine receptor stimulates phospholipase D activity: a novel signaling pathway for dopamine. Mol Pharmacol 58: 455–462, 2000.
61. Lee KS, Buck M, Houglum K, Chojkier M. Activation of hepatic stellate cells by TGF alpha and collagen type I is mediated by oxidative stress through c-myb
expression. J Clin Invest 96:2461-2468 ,1995.
62. Bachem MG, Melchior R, Gressne AM. The role of thrombocytes in liver
fibrogenesis: effects of platelet lysate and thrombocyte-derived growth factors on the
92
mitogenic activity and glycosaminoglycan synthesis of cultured rat liver fat storing cells. J Clin Chem Clin Biochem 27:555-565 ,1989.
63. Gressner AM. Cytokines and cellular crosstalk involved in the activation of fat-storing cells. Hepatology 22:28-36 ,1995.
64. Fiorucci S, Antonelli E, Morelli A. Nitric oxide and portal hypertension: a nitric oxide-releasing derivative of ursodeoxycholic acid that selectively releases nitric oxide in the liver. Digestive and Liver Disease 35:S61-S69,2003.
65. Vallar L and Meldolesi J. Mechanisms of signal transduction at the dopamine D2 receptor. Trends Pharmacol Sci 10: 74–77, 1989.
66. Pinzani M, Failli P, Ruocco C, Casini A, Milani S, Baldi E, Giotti A, Gentilini P.
Fat-storing cells as liver-specific pericytes. Spatial dynamics of agonist- stimulated intracellular calcium transients. J Clin Invest 90:642-646 ,1992.
67. Tao J, Mallat A, Gallois C, Behnadani S, Mery PF, Nhieu JT, Pavoine C, Lotersztajn S. Biological effects of C-type natriuretic peptide in human myofibroblastic hepatic stellate cells. Biol Chem 274:23761-23769 ,1999.
68. Rockey DC, Fouassier L, Chung JJ, Carayon A, Vallee P, Rey C, Housset C.
Cellular localization of endothelin-1 and increased production in liver injury in the rat:
potential for autocrine and paracrine effects on stellate cell. Hepatology 27:472-480 ,1998.
93
69. Callier S, Snapyan M, Le Crom S, Prou D, Vincent JD, Vernier P. Evolution and cell biology of dopamine receptors in vertebrates. Biol Cell 95:489–502, 2003.
70. Enjalbert A. Multiple transduction mechanisms of dopamine, somatostatin and angiotensin II receptors in anterior pituitary cells. Horm Res 31:6–12, 1989.
71.Parola M,Leonarduzzi G,Robino,Poli G.On the role of liver damage induced long standing cholestasis.Free Radical Biol Med 20:351-359,1996.
72. Carvey PM, Punati A. Progressive dopamine neuron loss in Parkinson’s disease:
the multiple hit hypothesis: Cell Transplant 15:239–250, 2006.
73. Willner P. The dopamine hypothesis of schizophrenia: current status, future prospects. Int Clin Psychopharmacol 12:297–308, 1997.
74.Sokl RJ, Winklhofer-Roob B, Mckim JM, Devereaux MW. Generation of hydroperoxides in isolated rat hepatocyte and hepatic mitochondria exposed to hydrophobic bile acid. Gastroenternology 109:1249-1256,1995.
75. Marzioni M, Glaser S, Francis H, Marucci L, Benedetti A, Alvaro D, Taffetani S, Ueno Y, Roskams T, Phinizy JL, Venter J, Fava G, LeSage GD, Alpini G.
Autocrine/paracrine regulation of the growth of the biliary tree by the neuroendocrine hormone serotonin. Gastroenterology 128:121–137, 2005.
76.Calumus Y, Guechot J, Podevin P, Connefis MT, Giboudeau J. Differential effects
94
of chenodeoxycholic and ursodeoxycholic acids on IL-1,-6 and TNF-α production by monocyte. Hepatology 16:719-723,1992.
77. Glaser S, Benedetti A, Marucci L, Alvaro D, Baiocchi L, Kanno N, Caligiuri A, Phinizy JL, Chowdhury U, Papa E, LeSage G. Gastrin inhibits cholangiocyte growth in bile duct-ligated rats by interaction with cholecystokinin-B /Gastrin receptors via D-myoinositol 1,4,5-triphosphate-, Ca2+, and protein kinase C alpha dependent mechanisms. Hepatology 32:17–25, 2000.
78. Glaser SS, Rodgers RE, Phinizy JL, Robertson WE, Lasater J, Caligiuri A, Tretjak Z, LeSage GD, Alpini G. Gastrin inhibits secretin-induced ductal secretion by
interaction with specific receptors on rat cholangiocytes. Am J Physiol 273:
G1061–G1070, 1997.
79. LeSage G, Glaser S, Alpini G. Regulation of cholangiocyte proliferation. Liver 21:73–80, 2001.
80. Francis H, Glaser S, Ueno Y, Lesage G, Marucci L, Benedetti A, Taffetani S, Marzioni M, Alvaro D, Venter J, Reichenbach R, Fava G, Phinizy JL, Alpini G.
cAMP stimulates the secretory and proliferative capacity of the rat intrahepatic biliary epithelium through changes in the PKA/Src/MEK/ERK1/2 pathway. J Hepatol
41:528–537, 2004.
81. Qi Li , Gang Lu , G.E, Mak , John A ,Rudd ,The usefulness of the spontaneously hypertensive rat to model attention-deficit/hyperactivity disorder (ADHD) may be
95
explained by the differential expression of dopamine-related genes in the brain . Neurochem Int 50(6):848-857,2007
82. Autelitano DJ, and van den Buuse M. Concomitant up-regulation of
proopiomelanocortin and dopamine D2-receptor gene expression in the pituitary intermediate lobe of the spontaneously hypertensive rat. J Neuroendocrinol 9:
255-262, 1997.
83.Wu J. and Norton PA. Animal models of liver fibrosis. Scand J Gastroenterol Dec;31(12):1137-43. 1996..