黄芩汤有效部位组方抗大鼠溃疡性结肠炎的实验研究
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摘要
溃疡性结肠炎(Ulcerative Colitis, UC)是最严重的胃肠道疾病之一，近年来其发病率逐渐升高，病因及确切发病机制至今未明，一般认为涉及到遗传、免疫、感染、精神等多方面的因素。本病的临床表现具备炎症性肠病的特点，可见脓血便或粘液血便、里急后重，或伴腹痛、发热等症状。本病常突然起病，病情轻重悬殊，多数病程缓慢，有反复发作倾向，少数病例急性暴发，病情凶险。由于本病治愈难度大，且常易复发，并与结肠癌的发病存在一定的关系，因此被世界卫生组织列为现代难治病之一。西药在治疗本病上大多存在停药后易复发，长期用药副反应多，部分顽固性病例疗效并不理想等缺点。因此寻找更为有效、副作用少的药物成为当今的研究重点。中药在治疗溃疡性结肠炎方面有显著优势，具有较突出的开发研究价值和广阔的前景。
本研究在系统整理古今文献的基础上，结合导师的临床经验，以中药复方的有效成分研究思路为依托，就黄芩汤及其单味药有效部位组方对大鼠实验性溃疡性结肠炎的作用进行了药效学研究、拆方研究及疗效机制研究。
药效学研究结果表明，黄芩汤及其单味药有效部位组方都具有较好的抗炎、止泻、镇痛作用，并可改善UC大鼠的一般状况，对UC大鼠的病理组织学改变也有较好的修复作用。
拆方研究结果表明，黄芩汤单味药有效部位的各组方均有不同程度的抗炎、止泻、镇痛作用，其中以黄芩苷+甘草酸+白芍总甙十大枣cAMP组效果最佳。由此初步确认黄芩苷、甘草酸、白芍总甙，大枣cAMP是黄芩汤治疗溃疡性结肠炎的主要物质基础。
黄芩汤有效部位组方治疗UC大鼠作用机制的研究结果表明，UC大鼠的外周血IL-1β含量显著升高，进一步证实了 IL-1β在溃疡性结肠炎发展过程中的重要作用。IL-4具有下行调节作用，可抑制IL-1β产量，抑制超氧化物阴离子形成。本实验表明UC大鼠外周血IL-4含量显著降低，同时结肠组织中SOD的活力也降低，这在一定程度上加重了IL-1β等细胞因子的致炎作用和氧自由基对细胞的损伤，MDA含量的升高则证实了这一点。UC大鼠经黄芩汤有效部位组方治疗后，IL-1β和MDA含量降低，而IL-4和SOD含量升高，炎症损伤程度也有明显减轻。因此，黄芩汤有效部位组方对IL-1β、IL-4、SOD、MDA均有一定的调节作用，对UC大鼠的治疗是有效的，并从细胞因子和自由基角度说明了本方的作用机制，反映出中药多环节、多途径、多靶点的作用特点。
Ulcerative colitis (UC) is one of the most serious gastrointestinal disease. Incidence of UC gradually increases with years. The etiological factor and pathogenesis remain unknown. The major factors generally include heredity, immune, infection and psychosomatic theory. The major symptoms of UC include diarrhea, rectal bleeding, the passage of mucus, tenesmus and abdominal pain, those symptoms is characteristic of inflammatory bowel disease. The onset of UC is acute and patient's condition is great disparity. In general, UC's progress is slow, but it tends to relapse. Severity condition of this disease may be found in some case who are acute. UC has been listed as refractory disease by WHO because it's treatment is very difficulty and frequently relapse, meanwhile, it correlates with cancer of colon. There are some deficiencies of UC's treatment through western medicine, such as frequently relapse after drug withdrawal, there are some side effect after taking medicine in a long time, there is no good effect in refractory case. So, it is the most important research to find effective drug. There are significant superiority, prominent investigation value and wide prospect in the aspect treatment of UC by Chinese medicine.
This paper base on systemically arranging literature and tutor's clinic experience, meanwhile, depend on the ways of thinking in the active elements of Chinese medicine research. Pharmacodynamics, taking prescription apart and curative mechanism that compound elements of HuangQinTang and HuangQin Tang treat experimental ulcerative colitis on rat were observed.
Pharmacodynamics result show that compound elements of HuangQinTang and HuangQin Tang have good effect of anti-inflammatory, antidiarrhea and relieve pain, meanwhile, it can improve the general condition and histopathologic condition.
Taking prescription apart result show that compound elements of HuangQinTang and HuangQin Tang have good effect of anti-inflammatory, antidiarrhea and relieve pain on some extent. The group of Baicalin + Glycyrrhizic acid + Panglycoside of white peony root + cAMP of jujube have the best effect in all group. So, the main substance that HuangQin Tang treat UC are Baicalin, Glycyrrhizic acid, Panglycoside of white peony root and cAMP of jujube.
The curative mechanism that compound elements of HuangQinTang treat UC show that IL-1 , IL-4, SOD, MDA had significant difference between model group and normal group ( P < 0.01 ) .Meanwhile,the medium dosage group of compound elements
Abstract
of HuangQinTang can significantly decrease the content of IL-1 , MDA and increase the content of IL-4, SOD,which significantly differs from those of the model group ( P
本研究在系统整理古今文献的基础上，结合导师的临床经验，以中药复方的有效成分研究思路为依托，就黄芩汤及其单味药有效部位组方对大鼠实验性溃疡性结肠炎的作用进行了药效学研究、拆方研究及疗效机制研究。
药效学研究结果表明，黄芩汤及其单味药有效部位组方都具有较好的抗炎、止泻、镇痛作用，并可改善UC大鼠的一般状况，对UC大鼠的病理组织学改变也有较好的修复作用。
拆方研究结果表明，黄芩汤单味药有效部位的各组方均有不同程度的抗炎、止泻、镇痛作用，其中以黄芩苷+甘草酸+白芍总甙十大枣cAMP组效果最佳。由此初步确认黄芩苷、甘草酸、白芍总甙，大枣cAMP是黄芩汤治疗溃疡性结肠炎的主要物质基础。
黄芩汤有效部位组方治疗UC大鼠作用机制的研究结果表明，UC大鼠的外周血IL-1β含量显著升高，进一步证实了 IL-1β在溃疡性结肠炎发展过程中的重要作用。IL-4具有下行调节作用，可抑制IL-1β产量，抑制超氧化物阴离子形成。本实验表明UC大鼠外周血IL-4含量显著降低，同时结肠组织中SOD的活力也降低，这在一定程度上加重了IL-1β等细胞因子的致炎作用和氧自由基对细胞的损伤，MDA含量的升高则证实了这一点。UC大鼠经黄芩汤有效部位组方治疗后，IL-1β和MDA含量降低，而IL-4和SOD含量升高，炎症损伤程度也有明显减轻。因此，黄芩汤有效部位组方对IL-1β、IL-4、SOD、MDA均有一定的调节作用，对UC大鼠的治疗是有效的，并从细胞因子和自由基角度说明了本方的作用机制，反映出中药多环节、多途径、多靶点的作用特点。
Ulcerative colitis (UC) is one of the most serious gastrointestinal disease. Incidence of UC gradually increases with years. The etiological factor and pathogenesis remain unknown. The major factors generally include heredity, immune, infection and psychosomatic theory. The major symptoms of UC include diarrhea, rectal bleeding, the passage of mucus, tenesmus and abdominal pain, those symptoms is characteristic of inflammatory bowel disease. The onset of UC is acute and patient's condition is great disparity. In general, UC's progress is slow, but it tends to relapse. Severity condition of this disease may be found in some case who are acute. UC has been listed as refractory disease by WHO because it's treatment is very difficulty and frequently relapse, meanwhile, it correlates with cancer of colon. There are some deficiencies of UC's treatment through western medicine, such as frequently relapse after drug withdrawal, there are some side effect after taking medicine in a long time, there is no good effect in refractory case. So, it is the most important research to find effective drug. There are significant superiority, prominent investigation value and wide prospect in the aspect treatment of UC by Chinese medicine.
This paper base on systemically arranging literature and tutor's clinic experience, meanwhile, depend on the ways of thinking in the active elements of Chinese medicine research. Pharmacodynamics, taking prescription apart and curative mechanism that compound elements of HuangQinTang and HuangQin Tang treat experimental ulcerative colitis on rat were observed.
Pharmacodynamics result show that compound elements of HuangQinTang and HuangQin Tang have good effect of anti-inflammatory, antidiarrhea and relieve pain, meanwhile, it can improve the general condition and histopathologic condition.
Taking prescription apart result show that compound elements of HuangQinTang and HuangQin Tang have good effect of anti-inflammatory, antidiarrhea and relieve pain on some extent. The group of Baicalin + Glycyrrhizic acid + Panglycoside of white peony root + cAMP of jujube have the best effect in all group. So, the main substance that HuangQin Tang treat UC are Baicalin, Glycyrrhizic acid, Panglycoside of white peony root and cAMP of jujube.
The curative mechanism that compound elements of HuangQinTang treat UC show that IL-1 , IL-4, SOD, MDA had significant difference between model group and normal group ( P < 0.01 ) .Meanwhile,the medium dosage group of compound elements
Abstract
of HuangQinTang can significantly decrease the content of IL-1 , MDA and increase the content of IL-4, SOD,which significantly differs from those of the model group ( P
引文
1 Papadakis KA. The etiology and pathogenesis of inflammatory bowel disease. Gastroenterol Clinic North Am, 1999, 28(1): 283-296
2 Karlinger K,Gyorke T, Mako E, et al. Theepidemiology and thepathogenesis of inflammatory bowel disease. Eur J Radiol, 2000, 35(3): 154-167
3 江学良，王志奎，秦成勇．中国溃疡性结肠炎的研究现状与对策．世界华人消化杂志，2000，8(6)：610-613
4 Curran ME, Lau KF, Hampe J, et al. Genetic analysis of inflammatory bowel disease in a large European cohort supports linkage to chromosomes 12 and 16. Gastroenterology, 1998, 115(5): 1286-1289
5 Satsangi J, Parkes M, Louis E, et al. Two stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7 and 12. Nat Genet, 1996, 14(2):199-202
6 Parkes M, Satsngi J, Jewell DP, et al. Ulcerative colitis is more strongly linked to chromosome 12 than Crohn' s disease. Gut, 2001, 49(2): 311
7 Tountas NA, Casini RV, Yang H, et al. Functional and ethnic association of allele 2 of the interleukin-1 receptor antagonist gene in ulcerative colitis. Gastroenterology, 1999, 117(4): 806-813
8 Carr I,Mayberry JF. The effects of migration on ulcerative colitis: a three-year prospective study among Europeans and first-and-second generation South Asians in Leicester (1991-1994). Am J Gastroenterol, 1999, 94(10):2918-2922
9 Irvine EJ, Farrokhyar F, Swarbrick ET. A critical review of epide miological studies in inflammatory bowel disease. Scand J Gastroenterol, 2001, 36(1): 2-15
10 Mayer L. IBD: immunologic research at the mount Sinai hospital. Mt Sinai J Med, 2000, 67(3):208-213
11 郝微微．溃疡性结肠炎发病机理的研究进展．陕西医学杂志，2002，31(12)：1100-1102
12 Hoffmann JC, Peters K, Henschke S, et al. Role of T lymphocyte in rat 2, 4, 6-trinitrobenzene sulphonic acid(TNBS) induced colitis: increased mortality after gammadeta T cell depletion and no effect of alphabeta T cell depletion. Gut, 2001, 48(4):489
13 Caradonna L, Amati L, Lella P, et al. Phagocytosis, killing, lymphocyte mediated antibacterial activity, serum autoantibodies and plasma endotoxins in inflammatory bowel disease. Am J Gastroenterol, 2000, 95(6): 1495
14 黄永平，张元德，邢玉馥，等．大鼠溃疡性结肠炎模型的建立与观察．白求恩医科大学，1995，21(4)：357-359
15 潘伯荣，吴秀华，薛芳芳，等．肠道炎症性疾病患者抑制细胞功能的初步研
究．新消化病学杂志，1995，3(1)：11-12
16 金航．国外医学中医中药分册．1995，17(1)：23-24(日)／松生恒夫／／临床上研究．1993，70(1)：331-334
17 高亚菲，李旭，朱昭明．明显溃疡性结肠炎患者外周血 NK 细胞活性的研究．西安医科大学学报，1994，15(4)：338-339
18 严瑾．炎性肠病与T细胞亚群比例失衡．国外医学·消化系疾病分册，1999，19(2)：83-87
19 Subrata G, Alan S, Anne F. Ulcerative colitis. 英国医学杂志中文版，2002，5(3):144-148
20 Mahida YR. The key role of macrophages in the immunopathogenesis of inflammatory bowel disease. Infiamm Bowel Dis, 2000, 6:21-33
21 Huang GT-J, Eckmann L, Savidge TC, et al. Infection of human intestinal epithelial cells with invasive bacteria upregulates apical intercellular adhesion molecule-1(ICAM-1) expression and neutrophil adhesion. J Clin Invest. 1996, 98:572
22 Binion DG, West GA, Ina K, et al. Enhanced leukocyte hinding by intestinal microvascular endothelial cells in inflammatory bowel disease. Gastroenterology, 1997, 112:1895
23 李国栋，陈思昶，王瑛．中药灌肠方法治疗溃疡性结肠炎临床观察及实验研究．中西医结合杂志，1989，9(10)：616
24 溃疡性结肠炎患儿的抗嗜中性粒细胞胞浆抗体，国外医学儿科学分册，1995，
25 Steven TR, Harley SL, Groom JS, et al. Anti-endothelial cell antibodies in inflammatory bowes disease. Dig Dis Sci, 1993, 38(3):426-432
26 刘新光，于涛，赵明辉，等．抗中性粒细胞胞浆抗体对溃疡性结肠炎的诊断价值．中华内科杂志，1999，38(7)：451
27 薛予萌，王秀珍．日本对溃疡性结肠炎病因病理研究的进展．中国肛肠病杂志，1991，(1)：35-36
28 巫协宁．炎症性肠病的研究现状．中华消化杂志，1990，10(2)：63-64
29 Xia B, Cmsius JBA, Meuwissen SGM, et al. Inflammatory bowel disease: definition, epidemiology, etiologic aspects, and immunogenetic studies. World Surg, 1998, 22: 382-389
30 Rogler G, Andus T, Cytokines in inflammatory bowel disease. World Surg, 1998, 22:382-389
31 Fiocchi C, Podolsky DK, Cytokines and growth factors in inflammatory bowel disease, In:Kirsner JB, Shorter YG, ed. Inflammatory Bowel Disease. 4th ed. Baltimore: Wilkins, 1995, 252-280
32 Fiocchi C. Cytokines and animal models:A combined path to inflammatory bowel disease pathogenesis.Gastroenterology, 1993, 104:1202-1206
33 Sartor RB. Cytokine in intestinal inflammation: Pathophysiological and clnical considerations. Gastroenterology, 1994, 106: 533-538
34 Mcalinclon ME, Hawkey CJ, Mahida YR. Expression of interleukin-1 β and inerleukin-1 βconverting enzyme by intestinal mactophages in health and inflammatory bowel disease. Gut, 1998, 42: 214-219
35 Manida YR, Wu K, Jewell DP. Enhanced production of interleukyn-1 β imononuclear cellsisolated from mueosa with active colitis and crohn' s disease. Gut, 1989, 30: 835-841
36 Andus T, Daig R, Vogl O, et al. Imbalance of the interleukin-1 system in colonic mucosa-association with intestinal inflammation and interleukin 1 receptor antagonist[corrected] genotype2. Gut, 1997, 41(5):651-657
37 Jshiguro Y. Mucosal proinflammatory cytokine production correlates with endoscopic activity of ulcerative colitis. J Gastroenterol, 1999, 34(4):66
38 毛一雷，杜顺达．炎性肠道疾病与免疫和介质的关系．中国实用外科杂志，2001，21(12)：747-749
39 Ferretti M, Casini-Raggi V, Pizarro TT, et al. Neutralization of endogenous IL-1 receptor antagonist exacerhates and prolongs inflammation ion rabbit immunecolitis. Clin Invest. 1994, 94:449-453
40 朱峰，钱家鸣，潘国宗，等．白细胞介素1β和白细胞介素8在实验性结肠炎发病中的作用及白细胞介素1受体拮抗剂治疗作用的探讨．中国医学科学院学报，1998，20：388-394
41 Reineeker HC, Steffen M, Witthoeft T, et al. Enhanced secretion of tumour nectosis factor-alpha, IL-6, and IL-1 β by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn' s disease. Clin Exp Innunol, 1993, 94:174-181
42 Almawi WY, Lipman ML, Stevens AC, et al. Abrogation of glucocorticosterid-mediated inhibition of T cell proliferation by the synergistic action of IL-1, IL-6 and TNF-α. J Immunol, 1991, 146: 3526-3529
43 Ixutani R, Ohyanagi H, Macdermott P, et al. Quantitative PCR for detection of femtogran quantities of interleukin-8 mRNA expression microbiol. Immunol, 1994, 38:233
44 Arai F, Takahashi T, Furukawa K, et al. Mucosal expression of interleukin-6 and interleukin-8 messenger RNA in ulcerative colitis and in Crohn' s. Dig Dis Sci, 1998, 43:2071-2079
45 Daig R, Aschenbrenner E, et al. Increased interleukin-8 expression in the colon mucosa of patients with inflammatory bowel disease. Gut, 1996, 38:216-222
46 李琪佳．细胞因子与溃疡性结肠炎．临床内科杂志，1997，14(6)：297-298
47 Ehrhardt RO, Ludviksson BR, Gray B, et al. Induction and prevention of
colonic inflammation in IL-2-deficient mice. Immunol, 1997, 158:566-573
48 Kullberg MC, Ward JM, Gorelick PL, et al. Helicobacter hepatieus triggers colitis in specific-pathogen-free interleukin-10(IL-10)-deficient mice through an IL-2 and gamma interferon-dependent mechanism. Infect Immunol, 1998, 66:5157-5166
49 彭仲生．炎症性肠病与细胞因子．国外医学内科学分册，2000，27( 6): 234-237
50 Sakai T, Kusugami K, Nishinara H, et al. Gastroenterology, 1998, 114:1237-1243
51 Barbulescu K, Becker C, Schlaak JF, et al. J Immunol, 1998.160(8):3642-3647
52 Takeuchi M, Nishizaki Y, Sano O, et al. Cell Tissue Res, 1997, 289:499-503
53 Breese J, Michie A, Nicholls W, et al. Tumor necrosis factor producing cells in the intestinal mucosa of children with inflammatory bowel disease. Gastroenterology, 1994, 106:1445-1452
54 Halstensen TS, Mollnes TE, Garred P, et al. Epithelial deposition of immunoglobulin G and activated complement(C3b and terminal complement complex) in ulcerative colitis. Gastroenterology. 1990, 98: 1264-1272
55 Potton JS, Peters PM, Mc Cabe J, et al. Development of partial tolerance to the gastrointestinal effects of high does of recombinant tumor necrosis factor-a in rodens. Clin Invest, 1987, 80: 1587-1595
56 Carol M, Lambrechts A, Van Gossum A, et al. Spontaneous secretion of interferon-γ and inerleukin-4 by human intraepithelial and lamina propria gut lymphocytes. Gut, 1998, 42:643-649
57 Fuss U, Neurath MF, Boirivant M, et al. Disperate CD4+ lmina propia(LP) lymphokine secretion profiles in inflammatory bowel disease. Immunol, 1996, 157:1261-1270
58 Reinecher HC, Lou EY, Ringler DJ, etal. Gastroenterology, 1995,108:40-50
59 Rogy MA, Beinhauer BG, Reinisch W, et al. Clinical protocol: transfer of inerleukin-4 and interleukin-10 in patients with severe inflammatory bowel disease of rectum. Human Gene Ther, 2000, 11(12): 1731
60 Niessner M, Volk BA. Altered Th1/Th2 cytokine profiles in the intestinal mucosa of patients with inflammatory bowel disease as assessed by quantitative reversed transcribed polymerase chain reaction(RT-PCR). Clin Exp Immunol, 1996, 101:428-435
61 Autschbach F, Braunstein J, Helmke B, et al. In situ expression of interleukin-10 in noninflamed human gut and in inflammatory bowel disease. Am J Pathol, 1998, 153:121-130
62 Schreiber S, Heimig T, Thiele HG, et al. Immunoregulatory role of interleukin-10 in patients with inflammatory bowel disease. Gastroenterology, 1995,
108:1434-1444
63 张晓峰．细胞因子与溃疡性结肠炎，2001，7(5)：465-468
64 Luck MS, Bass P. Effect of epidermal growth factor on experimental colitis in the rat. Phamacol Exp Ther, 1993, 264: 984-990
65 Procaccino F, Reishagen M, Hoffmam P, et al. Protective effect of epidermal growth factor in an experimental model of colitis in rats. Gastroenterology, 1994,107:12-17
66 Lawrance IC, Maxwell L, Doe W, et al. Inflammation location, but not type, determines the increase in TGF-beta 1 and IGF-1 expression and collagen deposition in IBD intestine. Inflamm Bowel Dis, 2001, 7(1):16
67 Sambuelli A, Diez RA, Sugai E, et al. Serum transforming growth factor-beta 1 levels increase in response to successful anti-inflammatory therapy in ulcerative colitis. Aliment Pharmacol Ther, 2000, 14(11):1443
68 Babyatsky MW, Rossiter G, Podulsky DK. Expression of transforming growth factor α and β in colonic mucosa in inflammatory bowel disease. Gastroenterology, 1996, 110:441
69 Taniguchi T, Tsukada H, Nakanura H, et al. Effect of the anti-ICAM-1 monocloned antibody on dextran sodium sulphate induced colitis in rats. J Gastroenterol-Hepatol, 1998, 13:945
70 Schurmann GM, et al. Gut, 1995, 36(3):411-418] [Leeuwenberg JFM, et al. Immunology, 1992, 77(2):543-549][Mackay CR, et al. J Cell Biol, 1994, 124(1):71-82
71 Henke CA, Roongta U, Mickelson DJ. CD44-related chondroitin sulfate proteoglycan, a cell surface receptor implicated with tumor cell invasion, mediateds endothelial cell migration fibrin and invasion into a fibrin matrix. J Clin Invest, 1996, 77:2544-2552
72 Heide KH, Mukder JWR, Ostermann E. Splice variants for the surface glycolprotein CD44 associated with metastatic tumor cells are expressed in normal tissues of humans and cynomoglus monkeys. Eur J Cancer, 1996, 31A:2385-2391
73 Resenberg WM, Prince C, Kaklamanis L, et al. Increased expression of CD44v6 and CD44v3 in ulcerative colitis but not Crohn' s disease. Lancet, 1995, 345: 1205-1209
74 Reinish W, Heider KH, Oberhuber G, et al. Poor diagnostic value of colonic CD44v6 expression and serum concertrations of its soluble from Crohn' s disease. Gut, 1998, 43:375-382
75 Fromont HG, Cezard JP, Aigrain Y, et al. CD44 variant expression in inflammatory colonic mucosa is not disease specific but associated with increased crypt cell proliferation. Histopathology, 1998, 32:317-321
76 Folwanczny C, Noehl N, Urban S, et al. Systemic levels of soluble CD44 variant(sCD44v6) in chronic inflammatory bowel disease. AJG, 1996, 91: 1681-1682
77 Kitano A, Oshitani N, Matsumoto T. CD44 variants in ulcerative colitis and Crohn' s disease. Lancet, 1996, 348: 266-267
78 江学良，权启镇，孙自勤，等．溃疡性结肠炎患者粘附分子的变化意义．华人消化杂志，1998，(6)：54-55
79 Seth R, Raymond FD, MakgobaMW. Circulating ICAM-1 isoforms: diagnostic prospects for inflammatory and immune disorders. Lancet, 1991, 338:83-89
80 Hynes RO. Integrins: versatility, modulation and signaling in cell adhesion. Cell, 1992, 69:11-25
81 江学良，权启镇，孙自勤，等．糖皮质激素对重度溃疡性结肠炎患者淋巴细胞粘附分子表达的影响．中国危重病急救医学，1998，(10)：366-368
82 Yacysky BR, Lazarovits A, Tsai V. Crohn' s disease, ulcerative colitis, and normal intestinal lymphocytes express integrins in dissimilar patterns. Gastroenterology, 1994, 107:1367-1371
83 邓火金，孙滨．糖皮质激素对哮喘患者 CD4 T 淋巴细胞和嗜酸细胞活化的影响．中华内科杂志，1997，(36)：7-10
84 Dustin ML, Springer TA. Lymphocyte function associated antigen-1 interaction with intracellular adhesion molecule-1 is one of at least three mechanism for lymphocyte adhesion to cultured endothelial cell. J Cell Biol, 1988, 107:321-329
85 Malizia G, Calabrease A, Cotton M. Expression of leukocyte adhesion moleculues by mucosal mononuclear phagocytes in inflammatory bowel disease. Gastroenterology, 1991, 100: 150-159
86 Okumura M, Fuji Y, Inada K. Both CD45RA+and CD45RO+subpopulations of CD8+T cells contain cells with high levels of LFA-1 expression, a phenotype of primed T cell. J Immnol, 1993, 150:270-273
87 陈骏，龚肖琦，钟纪根．糖皮质激素对免疫炎症过程中中性粒细胞粘附的影响．中华医学杂志，1995，75：270-273
88 江学良，权启镇，刘涛，等．溃疡性结肠炎研究的新进展．世界华人消化杂志，2000，8(2)：216-218
89 贺国斌．溃疡性结肠炎的血栓前状态与肝素治疗．国外医学内科学分册，2000，27(6)：238-241
90 Maciejewski J, Selleri C, Sato T, et al. Br J Haematol, 1995, 91:245-252
91 Anel A, Bufeme M, Boyer C, et al. Eur J Immunol, 1994, 24(10):2469-2476
92 Calera F, Garcia AB, Falcai RP, et al. Br J Haematol, 1998, 100:698-703
93 吴国新，阮长耿．血小板颗粒膜蛋白研究进展．中华血液杂志，1994，15(3)：162
94 江学良．溃疡性结肠炎患者血小板活化的检测．新消化病杂志，1997，11(5)：
736
95 Collins CE, Cihill MR, Newland AC, et al. Platelets circulation in an activated state in inflammatory bowel disease. Gastroenterology, 1994, 106(4):840-845
96 徐萍，吴锡琛．血小板功能障碍：炎症性肠病研究的一种新动向．国外医学消化系统疾病分册，1996，16(1)：43
97 Graef V, Baggenstoss AH, Sauer WG, et al. Venous thromblsis occurring in nonspecific ulcerative colitis. Arch Intern Med, 1996, 117(3):337
98 张连峰，田曙光，王国新．溃疡性结肠炎哈血小板功能状态的研究．中国实用内科杂志，2000，20(2)：98-99
99 张继平．溃疡性结肠炎的免疫学研究进展．中国误诊学杂志，2002，2(1)：57-59
100 Singer H, Kawka DW, Scott S, et al. Expression of inducible nitric oxide synthase and nitrotyrosine in colonic epithelium in inflammatory bowel disease. Gastroenterology, 1996, 111:871
101 Granger DN, Rutili G, Mcord JM. Superoxide radicals in felin intestinal ischemia. Gastroenterology, 1981, 81(1):22-25
102 Mulder JPJ. et al. Gut, 1991, 32:1146-1149
103 Tamai H, Levin S, Gagniella TS, et al. Free radicall induced colitis in the rat: a new model of inflammatory bowel disease. Gastroenterology, 1990, 98:A476
104 Rachimlewitz D, Stamler JS, Karmli F, et al. Peroxynitrite-induced rat colitis-a new model of colonic inflammation. Gastroenterology, 1993, 105:1681-1688
105 Tran DD, Visser TT, Pool MO, et al. Enhanced systemic nitric oxide production inflammatory bowel disease. Lancet, 1993, 341:1151
106 Oudkerk P, Bouma G, Visser TT, et al. Serum nitrate level in ulcerative colitis and Crohn' s disease. Scand J Gastroenterol, 1995, 30:784-788
107 Reynold PD, et al. Gut, 1994, 35(4):30-31
108 Zidek Z, et al. Int J Immunopharmacol, 1998, 20(7):319-343
109 Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: physiology, pathophsiology, and pharmacology. Pharmacol Rev, 1991, 43(2):109-142
110 Middleton SJ, Shorthouse M, Hunter JO. Increased nitric oxide synthesis in ulcerative colotis. Lancet, 1993, 341(8843):465-469
111 Boughton-Smith NK, Evans SM, Hawkey CJ, et al. Nitric oxide synthase activity in ulcerative colitis and Crohn' s disese. Lancet, 1993, 342(8866):338-344
112 欧阳钦．炎症性肠病的病因和发病机理．临床内科杂志，1998，15(2)：59
113 刘时光．炎症性肠病与细胞凋亡．国外医学·消化系统疾病分册，2001，10(2)：120
114 Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wild ranging implications in tissue kinctics. Br J Cancer, 1972, 26:239-245
115 Ueyama H, Kiyohara T, Sawada N, et al. High Fas ligand expression on lymphocytes in lesions of ulcerative colitis. Gut, 1998, 43:48-55
116 Strater J, Wellish I, Riedl S, et al. CD95 (Apo-1/Fas) mediated apoptosis in colon epithelial cell:a possible role in ulcerative colitis.J Pathol, 1996, 180:152-159
117 Iwamoto M, Koji T, Makiyama K, et al.Apoptosis of crypt epithelial cell in ulcerative colitis. J Pathol, 1996, 180:152-159
118 Krus MD, Shahsafaei A, Antin J, et al. Relation of Bcl-2 expression with apoptosis and proliferation in colonic graft versus host disease. Hum Pathol, 1998, 29:869-875
119 Sakai T, Kimura Y, Ohara KI, et al. Fas mediated cytotoxity by intestinal intraepithelial lymphocyte during acute graf-versus-host disease in mice. Gastroenterology, 1997, 113: 167-174
120 江学良，权启镇，孙自勤，等．溃疡性结肠炎患者淋巴细胞凋亡调控蛋白的表达．世界华人消化杂志，1997，7：902-905
121 彭黎明．细胞凋亡的基础与临床．北京：人民卫生出版社，2000，419
122 Iwamoto M. Apoptosis of erypt epithelial cell in ulcerative colitis. J Pathol, 1996; 180:152
123 Arai N. Enhanced epithelial cell turnover associated with P53 accumulation and high P21 WAF1/CIP1 expression in ulcerative colitis. Mod Pathol, 1999, 12:604
124 Suzuki A. Fas/Fas ligand expression and characteristics of primed CD45RO+T cells in the inflamed mucosa of ulcerative colitis. Scand J Gastroenterol, 2000, 35:1278
125 Fas S. A death factor and its receptor. Adv Immunol, 1994, 57:129
126 Asakura H. Gut-associated lymphoid tissues in ulcerative colitis. JPEN J Parenter Enteral Nutr, 1999, 276:25
127 Abreu-Martin MT.Fas activates the JNK pathway in human colonic epithelial cells: lack of a direct role in apoptosis. Am J Physiol, 1999, 276:599
128 Bregenholt S.The majority of lamina propria CD4(+)T-cells from scid mice with colitis undergo Fas-mediated apoptosis in vivo. Immunol Lett, 2001, 78:7
129 Fas S.A death factor and its receptor. Adv Immunol, 1994, 57:129
130 Coffey JC. Upregulation of Fas-Fas-L(CD95/CD95L)-mediated epithelial apoptosisa putative role in pouchitis? neJ Surg Res, 2001, 98:27
131 Rabago LR.Treatment of inoperable malignant gastric stenosis with self-expanding prosthesis. Gastroenterol Hepatol, 1999, 22:510
132 Ueyama H. High Fas ligand expression on lymphocytes in lesions of ulcerative colitis, 1998, 43:48
133 Sandoval M.Peroxynitrite-induced apoptosis in human intestinal epithelial cells is attenuated by mesalamine. Gastoenterology, 1997, 113:1480
134 Merritt AJ.Differential expression of bcl-2 in intestinal epithelia. Correlation with
attenuation of apoptosis in colonic crypts and the incidence of colonic neoplasia. J Cell Science, 1995, 108:2261
135 Krajewski S.Immunohistochemical determination of in vivo distribution of Bax, a dominant inhibitor of Bcl-2. Am J Pathol, 1994, 145:1323
136 Krajeuski S.Immunohistochemical analysis of in vivo patterns of Bax expression. Aproapoptotic member of the Bcl-2 protein family. Cancer Res, 1996, 56:2849
137 Itoh J. Decreased Bax expression by mucosal T cells favours resistance to apoptosis in Crohn's disease. Gut, 2001, 49(1):35
138 Iimura M. Bax is downregulated in inflamed colonic mucosa of ulcerative colitis. Gut, 2000, 47(2):228
139 Liu Z. IL-15 is highly expressed in inflammatory bowel disease and regulated local T cell-dependent cytokine pro-duction. J Immunol, 2000, 164:3608
140 Bulfonepaus SD.Interleukin-15 proteets from lethal apoptosis in vivo. Nat Med, 1997, 3:1124
141 戴育成．深入开展细胞凋亡的研究．中华血液病学杂志，1996，17(2)：617
142 Madsen KL, Doyle JS, Jewell LD, et al. Lactobacillus species prevents colitis in interleukin 10 gene-deficient mice. Gastroenterology. 1999, 116, 1107
143 彭仲生，胡品津．炎症性肠病发病机理研究概况．现代临床医学生物工程学杂志，2000，6(2)：77-80
144 Duchmann R, Schmitt E, Knolle P, et al. Tolerance towards resident intestinal flora in mice is abrogated in experimental colitis and restored by treatment with interleukin-10 or antibodiesto inerleukin-12. Eur J Immunol. 1996, 26:934
145 Casati J, Toner BB, Rooy ECD, et al. Concerns of patients with inflammatory bowel disease. A review of emerging themes. Dig Dis Sci, 2000, 45:26-31
146 Geerling BJ,Dagnelie PC,Badart-Smook A,et al. Diet as a risk factor for the development of ulcerative colitis.Am J Gastroenterol, 2000, 95(4): 1008-1013
147 Pullan RD, Rhodes J, Ganesh S, et al. Transdermal nicotine for active ulcerative colitis. N Engl J Med. 1994, 330:811
148 Beaugerie L, Massot N, Carbonnel F. Impact of cessation of smoking on the course of ulcerative colitis. Am J Gastroenterol,2001, 96(7):2113-2116
149 张新晨．溃疡性结肠炎诊治进展．医师进修杂志，2002，25(9)：54-56
150 Corrao G,Tragnone A,Caprilli R.Risk of inflammatory bowel disease attributabl to smoking, oral contraception and breast feeding in Italy: a nationwide case-control study. Cooperative Investigators of the Italian Group for the Study of the Colon and Retum(GISC).Int J Epidmiol, 1998, 27(3):397-404
151 Nos P, Hinojos AJ,Gomollo NF, et al. Budesonide in inflammatory bowel disease: a meta-analysis. Med Clin(Barc), 2001, 116(2):47-53
152 欧阳钦．溃疡性结肠炎的治疗．见：徐克成主编．消化病现代治疗．南京·江
苏科技出版社，1993，171
153 Robinson M. Optimizing therapy for inflammatory bowel disease. Am J Gastroenterol, 1997, 92(12):12-18
154 Gaimbaud R, Bertrand V, Chauvelot ML, et al. Network of inflammatory cytokines and correlation with disuse activity in ulcerative colitis. Am J Gastroenterol, 1998, 93(12):2397-2340
155 Kombluth A, Sachar DB. Ulcerative colitis practice guidelines in adults. Am J Gastroenterol, 1997, 92(2):204-207
156 Hanauer SB, Meyers S. Management of Crohn' s disease in adults. Am J Gastroenterol, 1997, 92(4):599
157 光山庆一．溃疡性结肠炎治疗最近话题．日本消化器病学会杂志，2000，97：10-18
158 Katz JA, Itoh J, Fiocchi C. Pathogenesis of inflammatory bowel disease. Curr Opin Gastroenterol, 1999, 15:291-297
159 Sandborn WJ, Hanauer SB. Antitumor necrosis factor therapy for inflammatory bowel disease: a review of agents, pharmacology, clinical results and safety. Inflamm Bowel Dis, 1999, 5:119-133
160 Mitsuyama K, Ide M, Nishiyama T. Role ofinterleukin-18 in a murine model of dextran sulfate sodium-induced colitis. Gastroenterology, 1998, 114:A1040
161 Su CG, Wen X, Bailey ST. A novel therapy for colitis utilizing PPAR-ligands to inhibit the epithelial inflammatory response. J Clin Invest, 1999, 104:383-389
162 Newberry RD, Stenson WF, Lorenz RG. Cyclo-oxygenase-2-dependent arachidonic acid metabolites are essential modulators of the intestinal immune response to dietary antigen. Nat Med, 1995, 5:900-906
163 Rampton DS, Phil D.New treatments for inflammatory bowel disease. World J Gastroentero, 1998, 4:369-376
164 Rampton DS. Management of difficult inflammatory bowel disease: where are we now? World J Gastroentero, 2000, 6:315-323
165 台卫平，罗和生．短链脂肪酸在溃疡性结肠炎病因及治疗中的作用．世界华人消化杂志，2000，(8)：96-97
166 Hoque SS, Ghosh S, Poxton IR. Role of endogenous luminal bascterial antigens in the pathogenesis of ulcerative colitis. Am J Gastroenterol, 1999, 94:2691
167 Cuffari C, Hunt S, Bayless T. Enhanced bioavailability of Imuran[TM] therapy in IBD: Correlations with treatment efficacy. Am J Gastroenterol, 1999, 94:2669
168 Shanahan F. Probiotics and inflammatory bowel disease: is there a scientific rationale? Inflamm Bowel Dis, 2000, 6:107-115
169 Sandbom WJ. Therapy for ulcerative colitis. Curr Opin Gastroenterol, 1998, 14:312-316
170 Madsen KL, Doyle JS, Jewell LD. Lactobacillus species prevent colitis in interleukin-10 gene-deficient mice. Gastroenterology, 1999, 116:1107-1114
171 江学良，刘涛．肝素治疗顽固性溃疡性结肠炎1例．世界华人消化杂志，1999，7：694
172 Green JT, Richardson C, Marshall RW, et al. Nitricoxide mediates a therapeutic effect of nicotine in ulcerative colitis. Ali Ment Pharmacol Ther,2000,14(11):1429-1434
173 Thomas GA, Rhodes J, Green JT. Role of smoking in inflammatory bowel disease: implications for therapy. Postgrad Med J(England), 2000, 76:273-279
174 Murata Y, Itoh J, Han Y, etal. The in vivo effect of nicotine on both Th1-and Th2-type response in murine models of inflammatory bowel disease. Gastrointestinal Function, 2000, 18:87-100
175 Murata Y, Itoh J, Han Y, et al. Nicotine ameliorate oxazolone-induced colitis of murine model by inhibition of increased IL-4 production. Gastroenterology, 2000, 118:721
176 Murata Y, Itoh J, Han Y, et al. Smoking and nicotine enhance Th1 response and suppress Th2 response on DSS-induced colitis of murine model. Gastroenterology, 2000, 118:720
177 Murata Y, Itoh J, Han Y, et al. Effect of nicotine on expression of nAchR on CD4+ cells of splenocytes and thymocytes in oxazolone-induced colitis of murine model. Gastroenterology, 2000, 118:5117
178 Wahl C, Liptay S, Adler G. Sulfasalazine: a potent and specific inhibitor of nuclear factor kappa B. J Clin Invest, 1998, 101:1163-1174
179 秦成勇，韩国庆．溃疡性结肠炎氨基水杨酸类药物和皮质类固醇药物治疗．世界华人消化杂志，2000，(8)：338-339
180 朱炳喜，吕愈敏，叶嗣懋．柳氮磺胺吡啶对大鼠乙酸性溃疡性结肠炎组织中氧自由基的影响．新消化病学杂志，1997，(5)：769-770
181 江学良．溃疡性结肠炎的诊断和治疗．世界华人消化杂志，2000，(8)：322-342
182 Prakash A, Markham A. Oral delayed-release mesalazine. A review of its use in ulcerative colitis and Crohn' s disease. Drugs, 1999, 57:383-408
183 Xu CT, Pan BR. Current medical therapy for ulcerative colitis. World J Gastroentero, 1999, 5:64-72
184 Rampton DS. Management of difficult inflammatory bowel disease: where are we now? World J Gastroentero, 2000, 6:315-323
185 李若平，王苑本．免疫抑制剂治疗炎症性肠病．华人消化杂志，1998．(6)：718-719
186 Taylor AC, Connell WR, Elliott, R. Oral cyclosporine in refractory inflammatory
bowel disease. Aust N Z J Med, 1998, 28:79-83
187 Haslam N, Hearing SD, Probert CS. Audit of cyclosporine use in inflammatory bowel disease: limited benefits, numerous side-effedts. Eur J Gastroenterol Hepatol, 2000, 12:657-660
188 Fellermann K, Ludwig D, Stahl M. Steroid-unresponseive acute attacks of inflammatory bowel disease: immunomodulation by tacrolimus(FK506). Am J Gastroenterol, 1998, 93:1860-1866
189 Rutgeerts P. Medical therapy of inflammatory bowel disease. Digestion, 1998, 59:453-469
190 Reimann J, Rudolphi A, Claesson MH. Novel experimental approaches in the study of the immunopathology in inflmmatory bowel disease.J Molecular Medicine, 1995,73:133
191 Takagi K,Okabe S,Saziki R.A new method for the production of chronic gastric ulcer in tats and the effect of several drugs on its healing. Jap J Pharmac,1970,19:418
192 夏冰，邓长生，易季云，等．大白鼠乙酸溃疡性结肠炎模型的制作与观察．中华病理学杂志，1992，21：311
193 Mann NS, Mann SK, Cheung EC.Fiberoptic colonoscopic study of experimental chemical colitis. Gastrointest Endosc,1980,26:28
194 Mann NS,Demers LM.Experimental colitis studied by colonscopy in the rat:effect of indomethcin. Gastrointest Endosc, 1983,29:77
195 Sharon P, Stenson WF. Metabolism of arachidonic acid in acetic acid colitis in rat:similarity to human inflammatory bowel disease. Gastroenterology, 1985,88:55
196 Noronha-Blob L,Lowe VC,Muhlhauser RO,et al.NPC15669,an inhibitor of neutrophil recruitment,is efficacious in acetic acid-induced colitis in rats. Gastroenterology, 1993,104,1021
197 林军，邓长生，陈德基，等．表皮生长因子、谷氨酰胺对鼠乙酸性结肠炎的保护作用．医学新知，1994，4：154
198 邓长生，夏冰，陈德基，等．超氧化物歧化酶对大鼠乙酸性结肠炎粘膜的保护作用．中华病理生理杂志，1994，10：23
199 Kitano A,Matsumoto T, Hiki M,et al.Epithelial dysplasia of the rabbit colon induced by degraded carrageenan. Cancer Res, 1986,46,1374
200 Onderdonk AB,Franklin ML,Cisneros RL,et al.Production of experimental ulcerative colitis in gnotobiotic guinea pigs with a simplified microflora. Infect Immun, 1981,32:225
201 Kitsukawa Y, Saito H,Suzuki Y, et al. Effect of ingestion of eicosapentaenoic acid ethyl ester on carrageenan induced colitis in Guinea Pigs. Gastroenterology, 1992,102:1859
202 Morris GP, Beck PL,Herridge MS,et al. Hapten induced model of chronic
inflammation and ulceration in the rat colon. Gastroenterology, 1989,96:795-811
203 Yamada T, Marshall S,Specian BD,et al.A comparative analysis of two models of colitis in rats. Gastroenterology, 1992,102:1524
204 MacDermott RP, ed.Inflammatory bowel disease: Current status and future approch. Amsterdam: Elsevier Science Publishers, 1988, 201
205 Vilaseca J, Salas A, Guamer F, et al. Participation of thromboxane and other eicosanoid synthesis in the course of experimental inflammatory colitis. Gastroenterology, 1990,98:269
206 Rachmilewitc D, Simon PL, Schwartz LW, et al. Inflammatory mediators of experimental colitis in rats. Gastroenterology, 1989,97:326
207 夏冰，于皆平．豚鼠溃疡性结肠炎模型．湖北医学院学报，1989，10：137
208 夏冰，黄梅芳，付苓，等．细胞免疫反应性溃疡性结肠炎模型．中华实验外科杂志，1992，9：130
209 连至诚，吴晓斌，林永成等．大鼠实验性结肠溃疡的肠道推进行为异常及二氢黄酮B_3等植物药的调整作用．中华病理生理杂志，1994，10：205
210 刘知惠，王志洁，代文体，等．溃疡性结肠炎的大白鼠模型观察．中华消化杂志，1998，8(5)：291
211 Reimann J,Rudolphi A,Tscheming T, et al. Selective engraftment of memory CD4 + T cell with an unusual recirculation pattern and a diverse T cell receptor-v β repertoire into scid mice.Eur J Immunol,1993,23:350
212 Morrissey PJ, Charrier, Braddy S,et al. CD4 + T cell that express high levels of CD45RB induce wasting disease when transferred into congenic severe combined immunodeficiant mice. Disease development is prevented by cotransfer of purified CD4 + T cell.J Exp Med, 1993,178:237
213 Pawrie F, Leach MW, Mauze S, et al. Inhibitor of TH1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhiCD4 + T cells. Immunity, 1994,1:553
214 Fowell D,Mason DW. Evidence that the T cell repertoire of normal rats contains cells with the potential to cause diabetes. Characterization of the CD4 + T cell subset that inhibits this autoimmune potential. J Exp Med, 1993,177:623
215 Fowell D,Mcknight AJ,Powrie F, et al.Subsets of CD4 + T cells and their roles in the induction and prevention of autoimmunity. Immunol Rev, 1991,123:37
216 Hammer RE,Maika SD,Richardson JA,et al.Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and Human β 2m:an animal model of HLA-B27-associated human disorders. Cell, 1990,63:1099
217 Taurog JD,Breban M,Simmons WA,et al.New experimental model of IBD:HLA-B27 transgenic.Res Cli Foru, 1993,15:173
218 Aiko S,Grisham MB.Spontaneous intestinal inflammation and nitric oxide
metabolism in HLA-B27 transgenic rats. Gastroenterology, 1995,109:142
219 Tygat GNJ,Bartelsman JFWM,Van Deventer SJH. eds. Inflammatory bowel disease.Dordrecht:Kluwer Academic Publishers, 1995,408～417
220 任晋斌，许卫红，马文运，等．柳氮磺吡啶栓治疗实验性结肠炎的药效学研究．中国医药工业杂志，1993，24(9)：408
221 徐叔云．药理实验方法学．人民卫生出版社出版．1991：1160
222 陈治水，聂志伟，张志清，等．溃疡性性结肠炎动物模型的复制与健脾灵复健作用的研究．中医药学报，1990，(2)：49
223 赵辉，周建中．溃疡性结肠炎的中药治疗及对结肠粘膜影响的研究．北京医科大学学报．1990，22(3)：197
224 陈治水，张志清，聂志伟，等．溃疡性结肠炎动物模型与健脾灵复健作用的研究．中西医结合杂志，1990，10(8)：488
225 马贵同．防治溃疡性结肠炎的临床与实验研究．上海中医药杂志。1996，(12)：2
226 马贵同．清肠栓对溃疡性结肠炎大鼠实验模型的影响．上海中医药杂志．1991，(9)：1-5
227 黄梅芳，付苓．溃疡性结肠炎的细胞毒实验研究及临床探讨．中华消化杂志．1990，10(5)：268
228 黄永年，张元德，刑玉馥．大鼠溃疡性结肠炎模型的建立与观察．中华病理学杂志．1995，24(6)：392
229 马贵同，赵鸿，程焕章，等．清肠栓治疗溃疡性结肠炎的临床和实验研究．上海中医药杂志，1991，(9)：1
230 吴焕淦，陈汉平，王楠，等．溃疡性结肠炎动物模型与隔艾灸治疗作用的形态学研究．中国针灸，1994，(3)：35
231 王玉良，谢杰，李显华，等．固本益肠片治疗实验性豚鼠脾虚型溃疡性结肠炎的研究．中国中西医结合杂志，1995，(2)：98
232 韩英，李世荣．溃疡性结肠炎治疗的新进展及新策略．世界华人消化杂志，2000，8(11)：1273-1275
2 Karlinger K,Gyorke T, Mako E, et al. Theepidemiology and thepathogenesis of inflammatory bowel disease. Eur J Radiol, 2000, 35(3): 154-167
3 江学良，王志奎，秦成勇．中国溃疡性结肠炎的研究现状与对策．世界华人消化杂志，2000，8(6)：610-613
4 Curran ME, Lau KF, Hampe J, et al. Genetic analysis of inflammatory bowel disease in a large European cohort supports linkage to chromosomes 12 and 16. Gastroenterology, 1998, 115(5): 1286-1289
5 Satsangi J, Parkes M, Louis E, et al. Two stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7 and 12. Nat Genet, 1996, 14(2):199-202
6 Parkes M, Satsngi J, Jewell DP, et al. Ulcerative colitis is more strongly linked to chromosome 12 than Crohn' s disease. Gut, 2001, 49(2): 311
7 Tountas NA, Casini RV, Yang H, et al. Functional and ethnic association of allele 2 of the interleukin-1 receptor antagonist gene in ulcerative colitis. Gastroenterology, 1999, 117(4): 806-813
8 Carr I,Mayberry JF. The effects of migration on ulcerative colitis: a three-year prospective study among Europeans and first-and-second generation South Asians in Leicester (1991-1994). Am J Gastroenterol, 1999, 94(10):2918-2922
9 Irvine EJ, Farrokhyar F, Swarbrick ET. A critical review of epide miological studies in inflammatory bowel disease. Scand J Gastroenterol, 2001, 36(1): 2-15
10 Mayer L. IBD: immunologic research at the mount Sinai hospital. Mt Sinai J Med, 2000, 67(3):208-213
11 郝微微．溃疡性结肠炎发病机理的研究进展．陕西医学杂志，2002，31(12)：1100-1102
12 Hoffmann JC, Peters K, Henschke S, et al. Role of T lymphocyte in rat 2, 4, 6-trinitrobenzene sulphonic acid(TNBS) induced colitis: increased mortality after gammadeta T cell depletion and no effect of alphabeta T cell depletion. Gut, 2001, 48(4):489
13 Caradonna L, Amati L, Lella P, et al. Phagocytosis, killing, lymphocyte mediated antibacterial activity, serum autoantibodies and plasma endotoxins in inflammatory bowel disease. Am J Gastroenterol, 2000, 95(6): 1495
14 黄永平，张元德，邢玉馥，等．大鼠溃疡性结肠炎模型的建立与观察．白求恩医科大学，1995，21(4)：357-359
15 潘伯荣，吴秀华，薛芳芳，等．肠道炎症性疾病患者抑制细胞功能的初步研
究．新消化病学杂志，1995，3(1)：11-12
16 金航．国外医学中医中药分册．1995，17(1)：23-24(日)／松生恒夫／／临床上研究．1993，70(1)：331-334
17 高亚菲，李旭，朱昭明．明显溃疡性结肠炎患者外周血 NK 细胞活性的研究．西安医科大学学报，1994，15(4)：338-339
18 严瑾．炎性肠病与T细胞亚群比例失衡．国外医学·消化系疾病分册，1999，19(2)：83-87
19 Subrata G, Alan S, Anne F. Ulcerative colitis. 英国医学杂志中文版，2002，5(3):144-148
20 Mahida YR. The key role of macrophages in the immunopathogenesis of inflammatory bowel disease. Infiamm Bowel Dis, 2000, 6:21-33
21 Huang GT-J, Eckmann L, Savidge TC, et al. Infection of human intestinal epithelial cells with invasive bacteria upregulates apical intercellular adhesion molecule-1(ICAM-1) expression and neutrophil adhesion. J Clin Invest. 1996, 98:572
22 Binion DG, West GA, Ina K, et al. Enhanced leukocyte hinding by intestinal microvascular endothelial cells in inflammatory bowel disease. Gastroenterology, 1997, 112:1895
23 李国栋，陈思昶，王瑛．中药灌肠方法治疗溃疡性结肠炎临床观察及实验研究．中西医结合杂志，1989，9(10)：616
24 溃疡性结肠炎患儿的抗嗜中性粒细胞胞浆抗体，国外医学儿科学分册，1995，
25 Steven TR, Harley SL, Groom JS, et al. Anti-endothelial cell antibodies in inflammatory bowes disease. Dig Dis Sci, 1993, 38(3):426-432
26 刘新光，于涛，赵明辉，等．抗中性粒细胞胞浆抗体对溃疡性结肠炎的诊断价值．中华内科杂志，1999，38(7)：451
27 薛予萌，王秀珍．日本对溃疡性结肠炎病因病理研究的进展．中国肛肠病杂志，1991，(1)：35-36
28 巫协宁．炎症性肠病的研究现状．中华消化杂志，1990，10(2)：63-64
29 Xia B, Cmsius JBA, Meuwissen SGM, et al. Inflammatory bowel disease: definition, epidemiology, etiologic aspects, and immunogenetic studies. World Surg, 1998, 22: 382-389
30 Rogler G, Andus T, Cytokines in inflammatory bowel disease. World Surg, 1998, 22:382-389
31 Fiocchi C, Podolsky DK, Cytokines and growth factors in inflammatory bowel disease, In:Kirsner JB, Shorter YG, ed. Inflammatory Bowel Disease. 4th ed. Baltimore: Wilkins, 1995, 252-280
32 Fiocchi C. Cytokines and animal models:A combined path to inflammatory bowel disease pathogenesis.Gastroenterology, 1993, 104:1202-1206
33 Sartor RB. Cytokine in intestinal inflammation: Pathophysiological and clnical considerations. Gastroenterology, 1994, 106: 533-538
34 Mcalinclon ME, Hawkey CJ, Mahida YR. Expression of interleukin-1 β and inerleukin-1 βconverting enzyme by intestinal mactophages in health and inflammatory bowel disease. Gut, 1998, 42: 214-219
35 Manida YR, Wu K, Jewell DP. Enhanced production of interleukyn-1 β imononuclear cellsisolated from mueosa with active colitis and crohn' s disease. Gut, 1989, 30: 835-841
36 Andus T, Daig R, Vogl O, et al. Imbalance of the interleukin-1 system in colonic mucosa-association with intestinal inflammation and interleukin 1 receptor antagonist[corrected] genotype2. Gut, 1997, 41(5):651-657
37 Jshiguro Y. Mucosal proinflammatory cytokine production correlates with endoscopic activity of ulcerative colitis. J Gastroenterol, 1999, 34(4):66
38 毛一雷，杜顺达．炎性肠道疾病与免疫和介质的关系．中国实用外科杂志，2001，21(12)：747-749
39 Ferretti M, Casini-Raggi V, Pizarro TT, et al. Neutralization of endogenous IL-1 receptor antagonist exacerhates and prolongs inflammation ion rabbit immunecolitis. Clin Invest. 1994, 94:449-453
40 朱峰，钱家鸣，潘国宗，等．白细胞介素1β和白细胞介素8在实验性结肠炎发病中的作用及白细胞介素1受体拮抗剂治疗作用的探讨．中国医学科学院学报，1998，20：388-394
41 Reineeker HC, Steffen M, Witthoeft T, et al. Enhanced secretion of tumour nectosis factor-alpha, IL-6, and IL-1 β by isolated lamina propria mononuclear cells from patients with ulcerative colitis and Crohn' s disease. Clin Exp Innunol, 1993, 94:174-181
42 Almawi WY, Lipman ML, Stevens AC, et al. Abrogation of glucocorticosterid-mediated inhibition of T cell proliferation by the synergistic action of IL-1, IL-6 and TNF-α. J Immunol, 1991, 146: 3526-3529
43 Ixutani R, Ohyanagi H, Macdermott P, et al. Quantitative PCR for detection of femtogran quantities of interleukin-8 mRNA expression microbiol. Immunol, 1994, 38:233
44 Arai F, Takahashi T, Furukawa K, et al. Mucosal expression of interleukin-6 and interleukin-8 messenger RNA in ulcerative colitis and in Crohn' s. Dig Dis Sci, 1998, 43:2071-2079
45 Daig R, Aschenbrenner E, et al. Increased interleukin-8 expression in the colon mucosa of patients with inflammatory bowel disease. Gut, 1996, 38:216-222
46 李琪佳．细胞因子与溃疡性结肠炎．临床内科杂志，1997，14(6)：297-298
47 Ehrhardt RO, Ludviksson BR, Gray B, et al. Induction and prevention of
colonic inflammation in IL-2-deficient mice. Immunol, 1997, 158:566-573
48 Kullberg MC, Ward JM, Gorelick PL, et al. Helicobacter hepatieus triggers colitis in specific-pathogen-free interleukin-10(IL-10)-deficient mice through an IL-2 and gamma interferon-dependent mechanism. Infect Immunol, 1998, 66:5157-5166
49 彭仲生．炎症性肠病与细胞因子．国外医学内科学分册，2000，27( 6): 234-237
50 Sakai T, Kusugami K, Nishinara H, et al. Gastroenterology, 1998, 114:1237-1243
51 Barbulescu K, Becker C, Schlaak JF, et al. J Immunol, 1998.160(8):3642-3647
52 Takeuchi M, Nishizaki Y, Sano O, et al. Cell Tissue Res, 1997, 289:499-503
53 Breese J, Michie A, Nicholls W, et al. Tumor necrosis factor producing cells in the intestinal mucosa of children with inflammatory bowel disease. Gastroenterology, 1994, 106:1445-1452
54 Halstensen TS, Mollnes TE, Garred P, et al. Epithelial deposition of immunoglobulin G and activated complement(C3b and terminal complement complex) in ulcerative colitis. Gastroenterology. 1990, 98: 1264-1272
55 Potton JS, Peters PM, Mc Cabe J, et al. Development of partial tolerance to the gastrointestinal effects of high does of recombinant tumor necrosis factor-a in rodens. Clin Invest, 1987, 80: 1587-1595
56 Carol M, Lambrechts A, Van Gossum A, et al. Spontaneous secretion of interferon-γ and inerleukin-4 by human intraepithelial and lamina propria gut lymphocytes. Gut, 1998, 42:643-649
57 Fuss U, Neurath MF, Boirivant M, et al. Disperate CD4+ lmina propia(LP) lymphokine secretion profiles in inflammatory bowel disease. Immunol, 1996, 157:1261-1270
58 Reinecher HC, Lou EY, Ringler DJ, etal. Gastroenterology, 1995,108:40-50
59 Rogy MA, Beinhauer BG, Reinisch W, et al. Clinical protocol: transfer of inerleukin-4 and interleukin-10 in patients with severe inflammatory bowel disease of rectum. Human Gene Ther, 2000, 11(12): 1731
60 Niessner M, Volk BA. Altered Th1/Th2 cytokine profiles in the intestinal mucosa of patients with inflammatory bowel disease as assessed by quantitative reversed transcribed polymerase chain reaction(RT-PCR). Clin Exp Immunol, 1996, 101:428-435
61 Autschbach F, Braunstein J, Helmke B, et al. In situ expression of interleukin-10 in noninflamed human gut and in inflammatory bowel disease. Am J Pathol, 1998, 153:121-130
62 Schreiber S, Heimig T, Thiele HG, et al. Immunoregulatory role of interleukin-10 in patients with inflammatory bowel disease. Gastroenterology, 1995,
108:1434-1444
63 张晓峰．细胞因子与溃疡性结肠炎，2001，7(5)：465-468
64 Luck MS, Bass P. Effect of epidermal growth factor on experimental colitis in the rat. Phamacol Exp Ther, 1993, 264: 984-990
65 Procaccino F, Reishagen M, Hoffmam P, et al. Protective effect of epidermal growth factor in an experimental model of colitis in rats. Gastroenterology, 1994,107:12-17
66 Lawrance IC, Maxwell L, Doe W, et al. Inflammation location, but not type, determines the increase in TGF-beta 1 and IGF-1 expression and collagen deposition in IBD intestine. Inflamm Bowel Dis, 2001, 7(1):16
67 Sambuelli A, Diez RA, Sugai E, et al. Serum transforming growth factor-beta 1 levels increase in response to successful anti-inflammatory therapy in ulcerative colitis. Aliment Pharmacol Ther, 2000, 14(11):1443
68 Babyatsky MW, Rossiter G, Podulsky DK. Expression of transforming growth factor α and β in colonic mucosa in inflammatory bowel disease. Gastroenterology, 1996, 110:441
69 Taniguchi T, Tsukada H, Nakanura H, et al. Effect of the anti-ICAM-1 monocloned antibody on dextran sodium sulphate induced colitis in rats. J Gastroenterol-Hepatol, 1998, 13:945
70 Schurmann GM, et al. Gut, 1995, 36(3):411-418] [Leeuwenberg JFM, et al. Immunology, 1992, 77(2):543-549][Mackay CR, et al. J Cell Biol, 1994, 124(1):71-82
71 Henke CA, Roongta U, Mickelson DJ. CD44-related chondroitin sulfate proteoglycan, a cell surface receptor implicated with tumor cell invasion, mediateds endothelial cell migration fibrin and invasion into a fibrin matrix. J Clin Invest, 1996, 77:2544-2552
72 Heide KH, Mukder JWR, Ostermann E. Splice variants for the surface glycolprotein CD44 associated with metastatic tumor cells are expressed in normal tissues of humans and cynomoglus monkeys. Eur J Cancer, 1996, 31A:2385-2391
73 Resenberg WM, Prince C, Kaklamanis L, et al. Increased expression of CD44v6 and CD44v3 in ulcerative colitis but not Crohn' s disease. Lancet, 1995, 345: 1205-1209
74 Reinish W, Heider KH, Oberhuber G, et al. Poor diagnostic value of colonic CD44v6 expression and serum concertrations of its soluble from Crohn' s disease. Gut, 1998, 43:375-382
75 Fromont HG, Cezard JP, Aigrain Y, et al. CD44 variant expression in inflammatory colonic mucosa is not disease specific but associated with increased crypt cell proliferation. Histopathology, 1998, 32:317-321
76 Folwanczny C, Noehl N, Urban S, et al. Systemic levels of soluble CD44 variant(sCD44v6) in chronic inflammatory bowel disease. AJG, 1996, 91: 1681-1682
77 Kitano A, Oshitani N, Matsumoto T. CD44 variants in ulcerative colitis and Crohn' s disease. Lancet, 1996, 348: 266-267
78 江学良，权启镇，孙自勤，等．溃疡性结肠炎患者粘附分子的变化意义．华人消化杂志，1998，(6)：54-55
79 Seth R, Raymond FD, MakgobaMW. Circulating ICAM-1 isoforms: diagnostic prospects for inflammatory and immune disorders. Lancet, 1991, 338:83-89
80 Hynes RO. Integrins: versatility, modulation and signaling in cell adhesion. Cell, 1992, 69:11-25
81 江学良，权启镇，孙自勤，等．糖皮质激素对重度溃疡性结肠炎患者淋巴细胞粘附分子表达的影响．中国危重病急救医学，1998，(10)：366-368
82 Yacysky BR, Lazarovits A, Tsai V. Crohn' s disease, ulcerative colitis, and normal intestinal lymphocytes express integrins in dissimilar patterns. Gastroenterology, 1994, 107:1367-1371
83 邓火金，孙滨．糖皮质激素对哮喘患者 CD4 T 淋巴细胞和嗜酸细胞活化的影响．中华内科杂志，1997，(36)：7-10
84 Dustin ML, Springer TA. Lymphocyte function associated antigen-1 interaction with intracellular adhesion molecule-1 is one of at least three mechanism for lymphocyte adhesion to cultured endothelial cell. J Cell Biol, 1988, 107:321-329
85 Malizia G, Calabrease A, Cotton M. Expression of leukocyte adhesion moleculues by mucosal mononuclear phagocytes in inflammatory bowel disease. Gastroenterology, 1991, 100: 150-159
86 Okumura M, Fuji Y, Inada K. Both CD45RA+and CD45RO+subpopulations of CD8+T cells contain cells with high levels of LFA-1 expression, a phenotype of primed T cell. J Immnol, 1993, 150:270-273
87 陈骏，龚肖琦，钟纪根．糖皮质激素对免疫炎症过程中中性粒细胞粘附的影响．中华医学杂志，1995，75：270-273
88 江学良，权启镇，刘涛，等．溃疡性结肠炎研究的新进展．世界华人消化杂志，2000，8(2)：216-218
89 贺国斌．溃疡性结肠炎的血栓前状态与肝素治疗．国外医学内科学分册，2000，27(6)：238-241
90 Maciejewski J, Selleri C, Sato T, et al. Br J Haematol, 1995, 91:245-252
91 Anel A, Bufeme M, Boyer C, et al. Eur J Immunol, 1994, 24(10):2469-2476
92 Calera F, Garcia AB, Falcai RP, et al. Br J Haematol, 1998, 100:698-703
93 吴国新，阮长耿．血小板颗粒膜蛋白研究进展．中华血液杂志，1994，15(3)：162
94 江学良．溃疡性结肠炎患者血小板活化的检测．新消化病杂志，1997，11(5)：
736
95 Collins CE, Cihill MR, Newland AC, et al. Platelets circulation in an activated state in inflammatory bowel disease. Gastroenterology, 1994, 106(4):840-845
96 徐萍，吴锡琛．血小板功能障碍：炎症性肠病研究的一种新动向．国外医学消化系统疾病分册，1996，16(1)：43
97 Graef V, Baggenstoss AH, Sauer WG, et al. Venous thromblsis occurring in nonspecific ulcerative colitis. Arch Intern Med, 1996, 117(3):337
98 张连峰，田曙光，王国新．溃疡性结肠炎哈血小板功能状态的研究．中国实用内科杂志，2000，20(2)：98-99
99 张继平．溃疡性结肠炎的免疫学研究进展．中国误诊学杂志，2002，2(1)：57-59
100 Singer H, Kawka DW, Scott S, et al. Expression of inducible nitric oxide synthase and nitrotyrosine in colonic epithelium in inflammatory bowel disease. Gastroenterology, 1996, 111:871
101 Granger DN, Rutili G, Mcord JM. Superoxide radicals in felin intestinal ischemia. Gastroenterology, 1981, 81(1):22-25
102 Mulder JPJ. et al. Gut, 1991, 32:1146-1149
103 Tamai H, Levin S, Gagniella TS, et al. Free radicall induced colitis in the rat: a new model of inflammatory bowel disease. Gastroenterology, 1990, 98:A476
104 Rachimlewitz D, Stamler JS, Karmli F, et al. Peroxynitrite-induced rat colitis-a new model of colonic inflammation. Gastroenterology, 1993, 105:1681-1688
105 Tran DD, Visser TT, Pool MO, et al. Enhanced systemic nitric oxide production inflammatory bowel disease. Lancet, 1993, 341:1151
106 Oudkerk P, Bouma G, Visser TT, et al. Serum nitrate level in ulcerative colitis and Crohn' s disease. Scand J Gastroenterol, 1995, 30:784-788
107 Reynold PD, et al. Gut, 1994, 35(4):30-31
108 Zidek Z, et al. Int J Immunopharmacol, 1998, 20(7):319-343
109 Moncada S, Palmer RMJ, Higgs EA. Nitric oxide: physiology, pathophsiology, and pharmacology. Pharmacol Rev, 1991, 43(2):109-142
110 Middleton SJ, Shorthouse M, Hunter JO. Increased nitric oxide synthesis in ulcerative colotis. Lancet, 1993, 341(8843):465-469
111 Boughton-Smith NK, Evans SM, Hawkey CJ, et al. Nitric oxide synthase activity in ulcerative colitis and Crohn' s disese. Lancet, 1993, 342(8866):338-344
112 欧阳钦．炎症性肠病的病因和发病机理．临床内科杂志，1998，15(2)：59
113 刘时光．炎症性肠病与细胞凋亡．国外医学·消化系统疾病分册，2001，10(2)：120
114 Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wild ranging implications in tissue kinctics. Br J Cancer, 1972, 26:239-245
115 Ueyama H, Kiyohara T, Sawada N, et al. High Fas ligand expression on lymphocytes in lesions of ulcerative colitis. Gut, 1998, 43:48-55
116 Strater J, Wellish I, Riedl S, et al. CD95 (Apo-1/Fas) mediated apoptosis in colon epithelial cell:a possible role in ulcerative colitis.J Pathol, 1996, 180:152-159
117 Iwamoto M, Koji T, Makiyama K, et al.Apoptosis of crypt epithelial cell in ulcerative colitis. J Pathol, 1996, 180:152-159
118 Krus MD, Shahsafaei A, Antin J, et al. Relation of Bcl-2 expression with apoptosis and proliferation in colonic graft versus host disease. Hum Pathol, 1998, 29:869-875
119 Sakai T, Kimura Y, Ohara KI, et al. Fas mediated cytotoxity by intestinal intraepithelial lymphocyte during acute graf-versus-host disease in mice. Gastroenterology, 1997, 113: 167-174
120 江学良，权启镇，孙自勤，等．溃疡性结肠炎患者淋巴细胞凋亡调控蛋白的表达．世界华人消化杂志，1997，7：902-905
121 彭黎明．细胞凋亡的基础与临床．北京：人民卫生出版社，2000，419
122 Iwamoto M. Apoptosis of erypt epithelial cell in ulcerative colitis. J Pathol, 1996; 180:152
123 Arai N. Enhanced epithelial cell turnover associated with P53 accumulation and high P21 WAF1/CIP1 expression in ulcerative colitis. Mod Pathol, 1999, 12:604
124 Suzuki A. Fas/Fas ligand expression and characteristics of primed CD45RO+T cells in the inflamed mucosa of ulcerative colitis. Scand J Gastroenterol, 2000, 35:1278
125 Fas S. A death factor and its receptor. Adv Immunol, 1994, 57:129
126 Asakura H. Gut-associated lymphoid tissues in ulcerative colitis. JPEN J Parenter Enteral Nutr, 1999, 276:25
127 Abreu-Martin MT.Fas activates the JNK pathway in human colonic epithelial cells: lack of a direct role in apoptosis. Am J Physiol, 1999, 276:599
128 Bregenholt S.The majority of lamina propria CD4(+)T-cells from scid mice with colitis undergo Fas-mediated apoptosis in vivo. Immunol Lett, 2001, 78:7
129 Fas S.A death factor and its receptor. Adv Immunol, 1994, 57:129
130 Coffey JC. Upregulation of Fas-Fas-L(CD95/CD95L)-mediated epithelial apoptosisa putative role in pouchitis? neJ Surg Res, 2001, 98:27
131 Rabago LR.Treatment of inoperable malignant gastric stenosis with self-expanding prosthesis. Gastroenterol Hepatol, 1999, 22:510
132 Ueyama H. High Fas ligand expression on lymphocytes in lesions of ulcerative colitis, 1998, 43:48
133 Sandoval M.Peroxynitrite-induced apoptosis in human intestinal epithelial cells is attenuated by mesalamine. Gastoenterology, 1997, 113:1480
134 Merritt AJ.Differential expression of bcl-2 in intestinal epithelia. Correlation with
attenuation of apoptosis in colonic crypts and the incidence of colonic neoplasia. J Cell Science, 1995, 108:2261
135 Krajewski S.Immunohistochemical determination of in vivo distribution of Bax, a dominant inhibitor of Bcl-2. Am J Pathol, 1994, 145:1323
136 Krajeuski S.Immunohistochemical analysis of in vivo patterns of Bax expression. Aproapoptotic member of the Bcl-2 protein family. Cancer Res, 1996, 56:2849
137 Itoh J. Decreased Bax expression by mucosal T cells favours resistance to apoptosis in Crohn's disease. Gut, 2001, 49(1):35
138 Iimura M. Bax is downregulated in inflamed colonic mucosa of ulcerative colitis. Gut, 2000, 47(2):228
139 Liu Z. IL-15 is highly expressed in inflammatory bowel disease and regulated local T cell-dependent cytokine pro-duction. J Immunol, 2000, 164:3608
140 Bulfonepaus SD.Interleukin-15 proteets from lethal apoptosis in vivo. Nat Med, 1997, 3:1124
141 戴育成．深入开展细胞凋亡的研究．中华血液病学杂志，1996，17(2)：617
142 Madsen KL, Doyle JS, Jewell LD, et al. Lactobacillus species prevents colitis in interleukin 10 gene-deficient mice. Gastroenterology. 1999, 116, 1107
143 彭仲生，胡品津．炎症性肠病发病机理研究概况．现代临床医学生物工程学杂志，2000，6(2)：77-80
144 Duchmann R, Schmitt E, Knolle P, et al. Tolerance towards resident intestinal flora in mice is abrogated in experimental colitis and restored by treatment with interleukin-10 or antibodiesto inerleukin-12. Eur J Immunol. 1996, 26:934
145 Casati J, Toner BB, Rooy ECD, et al. Concerns of patients with inflammatory bowel disease. A review of emerging themes. Dig Dis Sci, 2000, 45:26-31
146 Geerling BJ,Dagnelie PC,Badart-Smook A,et al. Diet as a risk factor for the development of ulcerative colitis.Am J Gastroenterol, 2000, 95(4): 1008-1013
147 Pullan RD, Rhodes J, Ganesh S, et al. Transdermal nicotine for active ulcerative colitis. N Engl J Med. 1994, 330:811
148 Beaugerie L, Massot N, Carbonnel F. Impact of cessation of smoking on the course of ulcerative colitis. Am J Gastroenterol,2001, 96(7):2113-2116
149 张新晨．溃疡性结肠炎诊治进展．医师进修杂志，2002，25(9)：54-56
150 Corrao G,Tragnone A,Caprilli R.Risk of inflammatory bowel disease attributabl to smoking, oral contraception and breast feeding in Italy: a nationwide case-control study. Cooperative Investigators of the Italian Group for the Study of the Colon and Retum(GISC).Int J Epidmiol, 1998, 27(3):397-404
151 Nos P, Hinojos AJ,Gomollo NF, et al. Budesonide in inflammatory bowel disease: a meta-analysis. Med Clin(Barc), 2001, 116(2):47-53
152 欧阳钦．溃疡性结肠炎的治疗．见：徐克成主编．消化病现代治疗．南京·江
苏科技出版社，1993，171
153 Robinson M. Optimizing therapy for inflammatory bowel disease. Am J Gastroenterol, 1997, 92(12):12-18
154 Gaimbaud R, Bertrand V, Chauvelot ML, et al. Network of inflammatory cytokines and correlation with disuse activity in ulcerative colitis. Am J Gastroenterol, 1998, 93(12):2397-2340
155 Kombluth A, Sachar DB. Ulcerative colitis practice guidelines in adults. Am J Gastroenterol, 1997, 92(2):204-207
156 Hanauer SB, Meyers S. Management of Crohn' s disease in adults. Am J Gastroenterol, 1997, 92(4):599
157 光山庆一．溃疡性结肠炎治疗最近话题．日本消化器病学会杂志，2000，97：10-18
158 Katz JA, Itoh J, Fiocchi C. Pathogenesis of inflammatory bowel disease. Curr Opin Gastroenterol, 1999, 15:291-297
159 Sandborn WJ, Hanauer SB. Antitumor necrosis factor therapy for inflammatory bowel disease: a review of agents, pharmacology, clinical results and safety. Inflamm Bowel Dis, 1999, 5:119-133
160 Mitsuyama K, Ide M, Nishiyama T. Role ofinterleukin-18 in a murine model of dextran sulfate sodium-induced colitis. Gastroenterology, 1998, 114:A1040
161 Su CG, Wen X, Bailey ST. A novel therapy for colitis utilizing PPAR-ligands to inhibit the epithelial inflammatory response. J Clin Invest, 1999, 104:383-389
162 Newberry RD, Stenson WF, Lorenz RG. Cyclo-oxygenase-2-dependent arachidonic acid metabolites are essential modulators of the intestinal immune response to dietary antigen. Nat Med, 1995, 5:900-906
163 Rampton DS, Phil D.New treatments for inflammatory bowel disease. World J Gastroentero, 1998, 4:369-376
164 Rampton DS. Management of difficult inflammatory bowel disease: where are we now? World J Gastroentero, 2000, 6:315-323
165 台卫平，罗和生．短链脂肪酸在溃疡性结肠炎病因及治疗中的作用．世界华人消化杂志，2000，(8)：96-97
166 Hoque SS, Ghosh S, Poxton IR. Role of endogenous luminal bascterial antigens in the pathogenesis of ulcerative colitis. Am J Gastroenterol, 1999, 94:2691
167 Cuffari C, Hunt S, Bayless T. Enhanced bioavailability of Imuran[TM] therapy in IBD: Correlations with treatment efficacy. Am J Gastroenterol, 1999, 94:2669
168 Shanahan F. Probiotics and inflammatory bowel disease: is there a scientific rationale? Inflamm Bowel Dis, 2000, 6:107-115
169 Sandbom WJ. Therapy for ulcerative colitis. Curr Opin Gastroenterol, 1998, 14:312-316
170 Madsen KL, Doyle JS, Jewell LD. Lactobacillus species prevent colitis in interleukin-10 gene-deficient mice. Gastroenterology, 1999, 116:1107-1114
171 江学良，刘涛．肝素治疗顽固性溃疡性结肠炎1例．世界华人消化杂志，1999，7：694
172 Green JT, Richardson C, Marshall RW, et al. Nitricoxide mediates a therapeutic effect of nicotine in ulcerative colitis. Ali Ment Pharmacol Ther,2000,14(11):1429-1434
173 Thomas GA, Rhodes J, Green JT. Role of smoking in inflammatory bowel disease: implications for therapy. Postgrad Med J(England), 2000, 76:273-279
174 Murata Y, Itoh J, Han Y, etal. The in vivo effect of nicotine on both Th1-and Th2-type response in murine models of inflammatory bowel disease. Gastrointestinal Function, 2000, 18:87-100
175 Murata Y, Itoh J, Han Y, et al. Nicotine ameliorate oxazolone-induced colitis of murine model by inhibition of increased IL-4 production. Gastroenterology, 2000, 118:721
176 Murata Y, Itoh J, Han Y, et al. Smoking and nicotine enhance Th1 response and suppress Th2 response on DSS-induced colitis of murine model. Gastroenterology, 2000, 118:720
177 Murata Y, Itoh J, Han Y, et al. Effect of nicotine on expression of nAchR on CD4+ cells of splenocytes and thymocytes in oxazolone-induced colitis of murine model. Gastroenterology, 2000, 118:5117
178 Wahl C, Liptay S, Adler G. Sulfasalazine: a potent and specific inhibitor of nuclear factor kappa B. J Clin Invest, 1998, 101:1163-1174
179 秦成勇，韩国庆．溃疡性结肠炎氨基水杨酸类药物和皮质类固醇药物治疗．世界华人消化杂志，2000，(8)：338-339
180 朱炳喜，吕愈敏，叶嗣懋．柳氮磺胺吡啶对大鼠乙酸性溃疡性结肠炎组织中氧自由基的影响．新消化病学杂志，1997，(5)：769-770
181 江学良．溃疡性结肠炎的诊断和治疗．世界华人消化杂志，2000，(8)：322-342
182 Prakash A, Markham A. Oral delayed-release mesalazine. A review of its use in ulcerative colitis and Crohn' s disease. Drugs, 1999, 57:383-408
183 Xu CT, Pan BR. Current medical therapy for ulcerative colitis. World J Gastroentero, 1999, 5:64-72
184 Rampton DS. Management of difficult inflammatory bowel disease: where are we now? World J Gastroentero, 2000, 6:315-323
185 李若平，王苑本．免疫抑制剂治疗炎症性肠病．华人消化杂志，1998．(6)：718-719
186 Taylor AC, Connell WR, Elliott, R. Oral cyclosporine in refractory inflammatory
bowel disease. Aust N Z J Med, 1998, 28:79-83
187 Haslam N, Hearing SD, Probert CS. Audit of cyclosporine use in inflammatory bowel disease: limited benefits, numerous side-effedts. Eur J Gastroenterol Hepatol, 2000, 12:657-660
188 Fellermann K, Ludwig D, Stahl M. Steroid-unresponseive acute attacks of inflammatory bowel disease: immunomodulation by tacrolimus(FK506). Am J Gastroenterol, 1998, 93:1860-1866
189 Rutgeerts P. Medical therapy of inflammatory bowel disease. Digestion, 1998, 59:453-469
190 Reimann J, Rudolphi A, Claesson MH. Novel experimental approaches in the study of the immunopathology in inflmmatory bowel disease.J Molecular Medicine, 1995,73:133
191 Takagi K,Okabe S,Saziki R.A new method for the production of chronic gastric ulcer in tats and the effect of several drugs on its healing. Jap J Pharmac,1970,19:418
192 夏冰，邓长生，易季云，等．大白鼠乙酸溃疡性结肠炎模型的制作与观察．中华病理学杂志，1992，21：311
193 Mann NS, Mann SK, Cheung EC.Fiberoptic colonoscopic study of experimental chemical colitis. Gastrointest Endosc,1980,26:28
194 Mann NS,Demers LM.Experimental colitis studied by colonscopy in the rat:effect of indomethcin. Gastrointest Endosc, 1983,29:77
195 Sharon P, Stenson WF. Metabolism of arachidonic acid in acetic acid colitis in rat:similarity to human inflammatory bowel disease. Gastroenterology, 1985,88:55
196 Noronha-Blob L,Lowe VC,Muhlhauser RO,et al.NPC15669,an inhibitor of neutrophil recruitment,is efficacious in acetic acid-induced colitis in rats. Gastroenterology, 1993,104,1021
197 林军，邓长生，陈德基，等．表皮生长因子、谷氨酰胺对鼠乙酸性结肠炎的保护作用．医学新知，1994，4：154
198 邓长生，夏冰，陈德基，等．超氧化物歧化酶对大鼠乙酸性结肠炎粘膜的保护作用．中华病理生理杂志，1994，10：23
199 Kitano A,Matsumoto T, Hiki M,et al.Epithelial dysplasia of the rabbit colon induced by degraded carrageenan. Cancer Res, 1986,46,1374
200 Onderdonk AB,Franklin ML,Cisneros RL,et al.Production of experimental ulcerative colitis in gnotobiotic guinea pigs with a simplified microflora. Infect Immun, 1981,32:225
201 Kitsukawa Y, Saito H,Suzuki Y, et al. Effect of ingestion of eicosapentaenoic acid ethyl ester on carrageenan induced colitis in Guinea Pigs. Gastroenterology, 1992,102:1859
202 Morris GP, Beck PL,Herridge MS,et al. Hapten induced model of chronic
inflammation and ulceration in the rat colon. Gastroenterology, 1989,96:795-811
203 Yamada T, Marshall S,Specian BD,et al.A comparative analysis of two models of colitis in rats. Gastroenterology, 1992,102:1524
204 MacDermott RP, ed.Inflammatory bowel disease: Current status and future approch. Amsterdam: Elsevier Science Publishers, 1988, 201
205 Vilaseca J, Salas A, Guamer F, et al. Participation of thromboxane and other eicosanoid synthesis in the course of experimental inflammatory colitis. Gastroenterology, 1990,98:269
206 Rachmilewitc D, Simon PL, Schwartz LW, et al. Inflammatory mediators of experimental colitis in rats. Gastroenterology, 1989,97:326
207 夏冰，于皆平．豚鼠溃疡性结肠炎模型．湖北医学院学报，1989，10：137
208 夏冰，黄梅芳，付苓，等．细胞免疫反应性溃疡性结肠炎模型．中华实验外科杂志，1992，9：130
209 连至诚，吴晓斌，林永成等．大鼠实验性结肠溃疡的肠道推进行为异常及二氢黄酮B_3等植物药的调整作用．中华病理生理杂志，1994，10：205
210 刘知惠，王志洁，代文体，等．溃疡性结肠炎的大白鼠模型观察．中华消化杂志，1998，8(5)：291
211 Reimann J,Rudolphi A,Tscheming T, et al. Selective engraftment of memory CD4 + T cell with an unusual recirculation pattern and a diverse T cell receptor-v β repertoire into scid mice.Eur J Immunol,1993,23:350
212 Morrissey PJ, Charrier, Braddy S,et al. CD4 + T cell that express high levels of CD45RB induce wasting disease when transferred into congenic severe combined immunodeficiant mice. Disease development is prevented by cotransfer of purified CD4 + T cell.J Exp Med, 1993,178:237
213 Pawrie F, Leach MW, Mauze S, et al. Inhibitor of TH1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhiCD4 + T cells. Immunity, 1994,1:553
214 Fowell D,Mason DW. Evidence that the T cell repertoire of normal rats contains cells with the potential to cause diabetes. Characterization of the CD4 + T cell subset that inhibits this autoimmune potential. J Exp Med, 1993,177:623
215 Fowell D,Mcknight AJ,Powrie F, et al.Subsets of CD4 + T cells and their roles in the induction and prevention of autoimmunity. Immunol Rev, 1991,123:37
216 Hammer RE,Maika SD,Richardson JA,et al.Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and Human β 2m:an animal model of HLA-B27-associated human disorders. Cell, 1990,63:1099
217 Taurog JD,Breban M,Simmons WA,et al.New experimental model of IBD:HLA-B27 transgenic.Res Cli Foru, 1993,15:173
218 Aiko S,Grisham MB.Spontaneous intestinal inflammation and nitric oxide
metabolism in HLA-B27 transgenic rats. Gastroenterology, 1995,109:142
219 Tygat GNJ,Bartelsman JFWM,Van Deventer SJH. eds. Inflammatory bowel disease.Dordrecht:Kluwer Academic Publishers, 1995,408～417
220 任晋斌，许卫红，马文运，等．柳氮磺吡啶栓治疗实验性结肠炎的药效学研究．中国医药工业杂志，1993，24(9)：408
221 徐叔云．药理实验方法学．人民卫生出版社出版．1991：1160
222 陈治水，聂志伟，张志清，等．溃疡性性结肠炎动物模型的复制与健脾灵复健作用的研究．中医药学报，1990，(2)：49
223 赵辉，周建中．溃疡性结肠炎的中药治疗及对结肠粘膜影响的研究．北京医科大学学报．1990，22(3)：197
224 陈治水，张志清，聂志伟，等．溃疡性结肠炎动物模型与健脾灵复健作用的研究．中西医结合杂志，1990，10(8)：488
225 马贵同．防治溃疡性结肠炎的临床与实验研究．上海中医药杂志。1996，(12)：2
226 马贵同．清肠栓对溃疡性结肠炎大鼠实验模型的影响．上海中医药杂志．1991，(9)：1-5
227 黄梅芳，付苓．溃疡性结肠炎的细胞毒实验研究及临床探讨．中华消化杂志．1990，10(5)：268
228 黄永年，张元德，刑玉馥．大鼠溃疡性结肠炎模型的建立与观察．中华病理学杂志．1995，24(6)：392
229 马贵同，赵鸿，程焕章，等．清肠栓治疗溃疡性结肠炎的临床和实验研究．上海中医药杂志，1991，(9)：1
230 吴焕淦，陈汉平，王楠，等．溃疡性结肠炎动物模型与隔艾灸治疗作用的形态学研究．中国针灸，1994，(3)：35
231 王玉良，谢杰，李显华，等．固本益肠片治疗实验性豚鼠脾虚型溃疡性结肠炎的研究．中国中西医结合杂志，1995，(2)：98
232 韩英，李世荣．溃疡性结肠炎治疗的新进展及新策略．世界华人消化杂志，2000，8(11)：1273-1275