溃疡性结肠炎应用5-ASA前药的疗效、机制及β2GPⅠ在发病中的作用研究
|
摘要
通过5-ASA新前体药物—巴柳氮对噁唑酮(OXZ)诱导的结肠炎小鼠模型进行干预,检测其对模型小鼠疾病活动指数、炎症指标、病理改变以及代表Th1、Th2型免疫反应的细胞因子的影响,从分子和蛋白水平、肠道局部免疫观察治疗效果并探讨可能的作用机制。同时应用巴柳氮对42例溃疡性结肠炎(UC)患者进行了临床观察并检测治疗前后细胞因子的变化,进一步探讨5-ASA可能的治疗作用机制,并从不同角度探讨了细胞因子在UC发病机制中的作用。通过检测UC患者血清抗β2糖蛋白Ⅰ抗体水平及β2糖蛋白Ⅰ与血小板结合水平探讨UC高凝状态的机制及其检测的临床意义。结果表明,我们成功建立了小鼠实验性结肠炎模型,巴柳氮对OXZ诱导的结肠炎具有良好的干预性作用,同时在临床观察中进一步证明了其疗效和安全性,其机制可能是通过适当的上调IL-10发挥治疗作用的。细胞因子IFN-γ在UC的发病机制中的作用可能不是必需的,而IL-4可能在UC的发生发展中的某一阶段,参与了发病。抗β2糖蛋白Ⅰ抗体可能和UC的发病机制有关,是其高凝状态的可能原因之一。β2糖蛋白Ⅰ与血小板结合水平可以在一定程度上预测UC患者血液的高凝状态。本课题为今后深入探讨UC的治疗药物、血液高凝状态及发病机制奠定了理论与实验基础。
Ulcerative colitis(UC) is an immunologic disease which is presumably resulted from the combined contribution of immunity,infection,environmental factors and genetic factors.But the exact etiology and pathogenesis is not clear at present.The role of immune factors is confirmed to be more important through many investigation,especially the disorder of cytokine(CK) network plays an important role in UC.It is more common in our country with the improvement of living standard and the change of diet.Because of the backwardness in investigation and slow progress in treatment,exploring the pathogenesis and new therapeutic tool,especially the safe and effective medicine,is of heated discussion.
Part one:Current treatment strategies endeavor to control the underlying inflammation,and conventional anti-inflammatory medicines including 5-aminosalicylic acid(5-ASA),glucocorticoid,immuno-suppressive agent and immunomodulator,which are used widely.However,they have many adverse effects and recurrent attacks might occur after discontinuation.5-ASA is the main therapeutic medicine to treat UC in the active period.In order to strengthen its efficacy and degrade its toxicity,researchers have been trying to find a more effective prodrug.Balsalazide is a new prodrug of 5-ASA.Compared with the congener drug salfasalazine(SASP),which is a prodrug of 5-ASA,balsalazide possesses more favourable drug tolerance because of the non-existence of SP,decreasing the adverse effect such as digestive symptom or drug hypersensitivity.To investigate about its therapeutic effect and safety on Chinese patients,and the possible mechanism, we conducted animal experiments and clinical observation systematically,which is the first time in China.The role of some cytokines in UC was also investigated from a different point of view.
Set up an oxazolone(OXZ)-induced colitis mice model and treat them with balsalazide,Compared with SASP.Detect their DAI score,macroscopic damage,histological score,MPO activity and the cytokines(IFN-γ、IL-4、IL-10)representing the Th1 or Th2 immunoreaction by enzyme-linked immunosorbent assay(ELISA) and RT-PCR to evaluate the colitis mice model’s value in this study;investigate the efficacy and immunologic mechanism of balsalazied.The result shows that the DAI score,macroscopic damage score,histological score,MPO activity in OXZ induced colitis were significantly higher than control group(P<0.05),and the IL-4 level was obviously higher than the control group,but IFN-γwas lower,which indicated the seting up of an OXZ induced colitis mice model successful.In the intervention experiment with medicine,all kinds of detect index in the balsalazide group were ameliorated obviously compared with normal sodium(NS) group and OXZ group(P<0.05),at the same time surpassing the SASP group.The level of IFN-γfrom LPMC in SASP and balsalazide group were not significantly different from OXZ group on days 3 and 7 post-intervention(P>0.05).The level of IFN-γmRNA by RT-PCR in SASP and balsalazide group were significantly higher on days 3(P<0.05),but the level decreased on days 7.The level of IL-4 from LPMC and IL-4mRNA in OXZ group were significantly higher than normal control group(P<0.05).The levels of IL-4 and IL-4mRNA were significantly decreased in balsalazide group on days 3 and 7 post-intervention(P<0.05).The level of IL-10 from LMPC were significantly higher than normal control group(P<0.05),but the level of IL-10mRNA were significantly higher on days 3,which no significantly different from normal control group on days 7.The levels of IL-10 from LPMC in SASP and balsalazide group were significantly higher than OXZ group(P<0.05),especially in balsalazide group(P<0.05).The level of IL-10mRNA in balsalazide group was significantly higher than OXZ group on days 3.Furthermore,the up-regulation was more obvious on days 7.Still,the level in SASP were inferior to alsalazide group.
The clinical trial portion:fouty-six patients with UC were randomly allocated into balsalazide group(n=24) or SASP group(n=22) in double-blind and double mimic trial and treated for eight weeks. The efficacy and adverse events of this drug were evaluated on the basis of the clinical improvements of symptoms and colonoscopic changes.And detecting the cytokines(IFN-γ、IL-4、IL-10)by ELISA and RT-PCR to investigate the efficacy and immunologic mechanism of balsalazied.Results:The rate of total efficiency rate in balsalazide group was higher than that in SASP group(96% vs 45%,P<0.01).The rate of drug adverse events in balsalazide group was lower than that in SASP group(4% vs 36%,P<0.05).The level of IFN-γmRNA in balsalazide and SASP group were not significantly different from normal control group prior therapy or after the weeks.The level of IL-4 from serum and IL-4mRNA from colon in all the groups were not significantly different(P>0.05).The levels of IL-10 from serum and IL-10mRNA from colon in balsalazide and SASP group were significantly higher than normal control group prior therapy and after 8 weeks,which were higher in balsalazide group than that in SASP group(P<0.05)as well.
Conclusions:The setting-up of the OXZ induced colitis mice model was successful;OXZ induced colitis is T helper cell type 2(Th2) inflammation,which is similar to the human UC;balsalazide has good therapeutic efficacy to the OXZ induced colitis mice model;balsalazide is obviously effective and safe in the treatment of mildly to moderately active UC,which surpass SASP.The mechanism may be through inducing the proper doses of IL-10 to educe the dominance of anti-inflammatory reaction and recover the balance of Th1/Th2;the role of IFN-γwas not significant,maybe not necessary in UC;IL-4 participate in the morbility of UC at some stage. Part two: It has been about 40 years since Beta2-glycoproteinⅠ(β2GPⅠ) was discovered,and for about 10 years it has been a focus.But most researches involved were about blood clotting,regulation of fibrolysis system and the relationship with SLE and Antiphospholipid(APS). In the various complications,thromboembolic disease is very severe and become one of the three causes of death in UC.The internal hypercoagulable state is likely to generate microthrombus,which may be one of the most important pathogenesis,and the creation of abnormal immune antibody should not be neglected.The relationship betweenβ2GPⅠand the hypercoagulable state in UC has not been reported yet while the connection ofβ2GPⅠand the function of the blood clotting and the change of platelet in UC patients remain to be explored.By ELISA and flow cytometry(FCM),we detected the level and clinical significance of anti-beta2-glycoproteinⅠantibodies(anti-β2GPⅠ) and combination rate betweenβ2GPⅠand platelet in UC patients.
The levels and the positive rates of anti-β2GPⅠof type IgM and IgG were detected in three groups:active UC,inactive UC and normal control groups by using ELISA.Results:1.There were both significant increase in the levels of IgM and IgG anti-β2GPⅠin active UC group and inactive UC group than in normal control group.There was also significant difference on the levels of anti-β2GPⅠof IgG between active UC group and inactive one(P<0. 05).2.On the positive rates of anti-β2GPⅠ,there was statistical significance between active UC group and inactive UC group;they had both remarkable difference with the normal control group,especially the active UC group(P<0.01).Combination rates ofβ2-GPⅠand platelet in the UC patients and in the normal control subjects were detected respectively.Results:There was significant difference in the combination rates ofβ2-GPⅠand platelet in the two UC groups and normal control group(P<0.01);meanwhile,there was also remarkable statistical significance between the active UC group and the remittent group(P<0.01).
Conclusion:anti-β2GPⅠmaybe play a role in the pathogenesis of UC and is a possible reason for its hypercoagulabale state;the examination of combination rates betweenβ2GPⅠand platelet in the UC patients may predict their hypercoagulabale state to some degree.
Our investigation established valuable theory evidence in both theory and practice for the screening of the efficacious drug,the study of hypercoagulable state and the pathogenesis of UC.
Ulcerative colitis(UC) is an immunologic disease which is presumably resulted from the combined contribution of immunity,infection,environmental factors and genetic factors.But the exact etiology and pathogenesis is not clear at present.The role of immune factors is confirmed to be more important through many investigation,especially the disorder of cytokine(CK) network plays an important role in UC.It is more common in our country with the improvement of living standard and the change of diet.Because of the backwardness in investigation and slow progress in treatment,exploring the pathogenesis and new therapeutic tool,especially the safe and effective medicine,is of heated discussion.
Part one:Current treatment strategies endeavor to control the underlying inflammation,and conventional anti-inflammatory medicines including 5-aminosalicylic acid(5-ASA),glucocorticoid,immuno-suppressive agent and immunomodulator,which are used widely.However,they have many adverse effects and recurrent attacks might occur after discontinuation.5-ASA is the main therapeutic medicine to treat UC in the active period.In order to strengthen its efficacy and degrade its toxicity,researchers have been trying to find a more effective prodrug.Balsalazide is a new prodrug of 5-ASA.Compared with the congener drug salfasalazine(SASP),which is a prodrug of 5-ASA,balsalazide possesses more favourable drug tolerance because of the non-existence of SP,decreasing the adverse effect such as digestive symptom or drug hypersensitivity.To investigate about its therapeutic effect and safety on Chinese patients,and the possible mechanism, we conducted animal experiments and clinical observation systematically,which is the first time in China.The role of some cytokines in UC was also investigated from a different point of view.
Set up an oxazolone(OXZ)-induced colitis mice model and treat them with balsalazide,Compared with SASP.Detect their DAI score,macroscopic damage,histological score,MPO activity and the cytokines(IFN-γ、IL-4、IL-10)representing the Th1 or Th2 immunoreaction by enzyme-linked immunosorbent assay(ELISA) and RT-PCR to evaluate the colitis mice model’s value in this study;investigate the efficacy and immunologic mechanism of balsalazied.The result shows that the DAI score,macroscopic damage score,histological score,MPO activity in OXZ induced colitis were significantly higher than control group(P<0.05),and the IL-4 level was obviously higher than the control group,but IFN-γwas lower,which indicated the seting up of an OXZ induced colitis mice model successful.In the intervention experiment with medicine,all kinds of detect index in the balsalazide group were ameliorated obviously compared with normal sodium(NS) group and OXZ group(P<0.05),at the same time surpassing the SASP group.The level of IFN-γfrom LPMC in SASP and balsalazide group were not significantly different from OXZ group on days 3 and 7 post-intervention(P>0.05).The level of IFN-γmRNA by RT-PCR in SASP and balsalazide group were significantly higher on days 3(P<0.05),but the level decreased on days 7.The level of IL-4 from LPMC and IL-4mRNA in OXZ group were significantly higher than normal control group(P<0.05).The levels of IL-4 and IL-4mRNA were significantly decreased in balsalazide group on days 3 and 7 post-intervention(P<0.05).The level of IL-10 from LMPC were significantly higher than normal control group(P<0.05),but the level of IL-10mRNA were significantly higher on days 3,which no significantly different from normal control group on days 7.The levels of IL-10 from LPMC in SASP and balsalazide group were significantly higher than OXZ group(P<0.05),especially in balsalazide group(P<0.05).The level of IL-10mRNA in balsalazide group was significantly higher than OXZ group on days 3.Furthermore,the up-regulation was more obvious on days 7.Still,the level in SASP were inferior to alsalazide group.
The clinical trial portion:fouty-six patients with UC were randomly allocated into balsalazide group(n=24) or SASP group(n=22) in double-blind and double mimic trial and treated for eight weeks. The efficacy and adverse events of this drug were evaluated on the basis of the clinical improvements of symptoms and colonoscopic changes.And detecting the cytokines(IFN-γ、IL-4、IL-10)by ELISA and RT-PCR to investigate the efficacy and immunologic mechanism of balsalazied.Results:The rate of total efficiency rate in balsalazide group was higher than that in SASP group(96% vs 45%,P<0.01).The rate of drug adverse events in balsalazide group was lower than that in SASP group(4% vs 36%,P<0.05).The level of IFN-γmRNA in balsalazide and SASP group were not significantly different from normal control group prior therapy or after the weeks.The level of IL-4 from serum and IL-4mRNA from colon in all the groups were not significantly different(P>0.05).The levels of IL-10 from serum and IL-10mRNA from colon in balsalazide and SASP group were significantly higher than normal control group prior therapy and after 8 weeks,which were higher in balsalazide group than that in SASP group(P<0.05)as well.
Conclusions:The setting-up of the OXZ induced colitis mice model was successful;OXZ induced colitis is T helper cell type 2(Th2) inflammation,which is similar to the human UC;balsalazide has good therapeutic efficacy to the OXZ induced colitis mice model;balsalazide is obviously effective and safe in the treatment of mildly to moderately active UC,which surpass SASP.The mechanism may be through inducing the proper doses of IL-10 to educe the dominance of anti-inflammatory reaction and recover the balance of Th1/Th2;the role of IFN-γwas not significant,maybe not necessary in UC;IL-4 participate in the morbility of UC at some stage. Part two: It has been about 40 years since Beta2-glycoproteinⅠ(β2GPⅠ) was discovered,and for about 10 years it has been a focus.But most researches involved were about blood clotting,regulation of fibrolysis system and the relationship with SLE and Antiphospholipid(APS). In the various complications,thromboembolic disease is very severe and become one of the three causes of death in UC.The internal hypercoagulable state is likely to generate microthrombus,which may be one of the most important pathogenesis,and the creation of abnormal immune antibody should not be neglected.The relationship betweenβ2GPⅠand the hypercoagulable state in UC has not been reported yet while the connection ofβ2GPⅠand the function of the blood clotting and the change of platelet in UC patients remain to be explored.By ELISA and flow cytometry(FCM),we detected the level and clinical significance of anti-beta2-glycoproteinⅠantibodies(anti-β2GPⅠ) and combination rate betweenβ2GPⅠand platelet in UC patients.
The levels and the positive rates of anti-β2GPⅠof type IgM and IgG were detected in three groups:active UC,inactive UC and normal control groups by using ELISA.Results:1.There were both significant increase in the levels of IgM and IgG anti-β2GPⅠin active UC group and inactive UC group than in normal control group.There was also significant difference on the levels of anti-β2GPⅠof IgG between active UC group and inactive one(P<0. 05).2.On the positive rates of anti-β2GPⅠ,there was statistical significance between active UC group and inactive UC group;they had both remarkable difference with the normal control group,especially the active UC group(P<0.01).Combination rates ofβ2-GPⅠand platelet in the UC patients and in the normal control subjects were detected respectively.Results:There was significant difference in the combination rates ofβ2-GPⅠand platelet in the two UC groups and normal control group(P<0.01);meanwhile,there was also remarkable statistical significance between the active UC group and the remittent group(P<0.01).
Conclusion:anti-β2GPⅠmaybe play a role in the pathogenesis of UC and is a possible reason for its hypercoagulabale state;the examination of combination rates betweenβ2GPⅠand platelet in the UC patients may predict their hypercoagulabale state to some degree.
Our investigation established valuable theory evidence in both theory and practice for the screening of the efficacious drug,the study of hypercoagulable state and the pathogenesis of UC.
引文
[1]Kawada M,Arihiro A,Mizoguchi E.Insights from advances in research of chemically induced experimental models of human inflammatory bowel disease.World J Gastroenterol,2007 Nov 14;13(42):5581-5593.
[2]Eaden J,Abrams K,Ekbom A,et al.Colorectal cancer prevention in ulcerative colitis:a case-control study.Aliment Pharmacol Ther,2000 Feb;14(2):145-153.
[3]Russel MG.Changes in the incidence of inflammatory bowel disease:what does it mean?Eur J Intern Med,2000 Aug;11(4):191-196.
[4]Orchard TR,Chua CN,Ahmad T,et al.Uveitis and erythema no-dosum in inflammatory bowel disease:clinical features and the role of HLA genes.Gastroenterology,2002 Sep;123(3):714-718.
[5]Ghosh S, Shand A, Ferguson A. Ulcerative colitis. Br Med J,2000 Apr 22;320(7242):1119-1123.
[6]Ardizzone S, Bianchi Porro G.Comparative tolerability of therapies for ulcerative colitis[J].Drug Saf,2002;25(8):561-582.
[7]Sandborn WJ.Oral 5-ASA Therapy in Ulcerative Colitis:What are the Implications of the New Formulations?J Clin Gastroenterol,2008 Apr;42(4):338-344.
[8]Farrell RJ. Peppercorn MA. Ulcerative colitis.Lancet,2002 Jan 26;359(9303):331-340.
[9]Xu CT, Meng SY, Pan BR. Drug therapy for ulcerative colitis.World J Gastroentero1,2004 Aug;10(16):2311-2317.
[10] 梁 毅 超 , 卿 三 华 . 溃 疡 性 结 肠 炎 的 外 科 治 疗 指 南 . 世 界 华 人 消 化 杂志,2006,14(21):2130-2134.
[11]Campbell DE, Berglindh T.Pharmacology of Olsalazine[J].Scand J Gastroenteol Suppl,1988;148:7-12.
[12]Wadorth AN,Fitton A.Olsalazine.A review of its pharmaco dynamic and pharmacokinetic properties and therapeutic potential in inflammatory bowel disease[J]. Drugs,1991Apr;41(4):647-664.
[13]Zhong YQ,Huang HR,Zhu ZH,et al.Effects of sulfasalazine on biopsy mucosalpathologies and histological grading of patients with active ulcerative colitis.World J Gastroenterol,2005 Jul;11(28):4435-4438.
[14]Chen QK,Yuan SZ,Wen ZF,et al.Characteristics and therapeutic efficacy of sulfasalazine in patients with mildly and moderately active ulcerative colitis.World J Gastroenterol,2005 Apr 28;11(16):2462-2466.
[15]Kamm MA.Review article:maintenance of remission in ulcerative colitis[J].Aliment Pharmacol Ther,2002 Jul;16 (Suppl4):21-24.
[16]胡伏莲,林庚金.美沙拉嗪治疗炎症性肠病的疗效及安全性-全国多中心临床研究[J].中国新药杂志,2001,10(3):201-203.
[17]Swaminath A,Kornbluth A.Optimizing drug therapy in inflammatory bowel disease.Curr Gastroenterol Rep,2007 Dec;9(6):513-520.
[18]Hanauer SB,Sandborn WJ,Kornbluth A,et al.Delayed-release oral mesalamine at4. 8 g/day (800 mg tablet) for the treatment of moderately active ulcerative colitis:the ASCEND II trial[J].Am J Gastroenterol,2005 Nov;100(11):2478-2485.
[19]Marteau P,Probert CS,Lindgren S,et a1.Combined oral and enema treatment with Pentasa(mesalazine) is superior to oral therapy alone in patients with extensive mild/moderate active ulcerative colitis: a randomised,double blind,placebo controlled study[J].Gut,2005 Jul;54(7):960-965.
[20]Gisbert JP,Gomollon F,Mate J,et al.Role of 5-aminosalicylicacid(5-ASA)in treatment of inflammatory bowel disease:a systematic review.Dig Dis Sci,2002 Mar;47(3):471-488.
[21]Frandsen NE,Saugmann S,Marcussen N.Acute interstitial nephritis associated with the use of mesalazine in inflammatory bowel disease.Nephron,2002 Sep;92(1):200-202
[22]Malchow H.A new mesalazine foam enema compared with a standard liquid enema in patients with active distal ulcerative colitis.Aliment Pharmacol Ther,2002 Mar;16(3):415-423.
[23]Hanauer SB.Medical therapy for ulcerative colitis 2004. Gastroenterol,2004 May; 126(6):1582-1592.
[24]Mahkam M.New pH-sensitive glycopolymers for colon-specific drug delivery.Drug Deliv,2007 Mar;14(3):147-153.
[25]蔡建庭,吴林峰,杜勤,等,奥沙拉秦钠胶囊和柳氮磺吡啶片治疗溃疡性结肠炎的随机对照研究[J].中华消化杂志,2001,21(10):593~595. Cai Jianting, Wu Linfeng, Du Qin,et al. Olaslazine Versus Sulfasalazine in the Treatment of Ulcerative Colitis: Randomized Controlled Clinical Trial[J]. Chinese Journal Digest,2001,21(10):593~595.
[26]Kruis W,Brandes JW,Schreiber S,et al.Olsalazine versus mesalazine in the treatment of mild to moderate ulcerative colitis.Aliment Pharmacol Ther,1998,12(8): 7607-7615.
[27]Prakash A,Markham A.Oral delayed-release mesalazine:a review of its use in ulcerative colitis and Crohn′s disease.Drugs,1999 Mar;57(3):383-408.
[28]Singer Mv,Schmausser H,Sch?nfeld G.Efficacy and tolerability of olsalazine (dipentum) in the treatment of patients with ulcerative colitis--results of a field study.Hepatogastroenterology,2006 May-Jun;53(69):317-321.
[29]Knoll U, Strauhs P, Schusser G,et al.Study of the plasma pharmacokinetics and faecal excretion of the prodrug olsalazine and it metabolites after oral administration to horses[J].J Vet Pharmaco Ther, 2002 Apr;25(2):135-143.
[30]Sandborn WJ,Hanauer SB.Systematic review:the pharmacokinetic profiles of oral mesalazine formulations and mesalazine pro-drugs used in the management of ulcerative colitis.Aliment Pharmacol Ther,2003 Jan;17(1):29-42.
[31]Stoa-Birketvedt G,Florholmen J.The systemic load and efficient delivery of active 5-aminosalicylic acid in patients with ulcerative colitis on treatment with olsalazine or mesalazine.Aliment Pharmacol Ther,1999;13(3):357-361.
[32]Kles KA,Vavricka SR,Turner JR,et al.Comparative analysis of the in vitro prosecretory effects of balsalazide,sulfasalazine,olsalazine,and mesalamine in rabbit distal ileum.Inflamm Bowel Dis,2005 Mar;11(3):253-257.
[33]Kornbluth A,Sachar DB. Ulcerative colitis.Am J Gastroenterol 1997;92(2):204-211.
[34]Ragunath K,Williams JG.Review article:balsalazide therapy in ulcerativecolitis[J].Aliment Pharmacol Ther,2001 Oct;15(10):1549-1554.
[35]王海鸥,韩伟,朱庆.巴柳氮钠研究情况综述.实用医技杂志,2003,10(5):531-533.
[36]Levine DS, Riff DS, Pruitt R,et al.A randomized,double blind,dose-response comparison of balsalazide (6.75 g), balsalazide (2.25 g), and mesalamine (2.4 g) in the treatment of active, mild-to-moderate ulcerative colitis.Am J Gastroenterol,2002 Jun;97(6):1398-1407.
[37]Mansfield JC, Giaffer MH, Cann PA,et al. A double-blind comparison of balsalazide, 6.75 g, and sulfasalazine, 3 g, as sole therapy in the management of ulcerative colitis.Aliment Pharmacol Ther. 2002 Jan;16(1):69-77.
[38]Stein RB,Hanauer SB.Comparative tolerability of treatments for inflammatory bowel disease.Drug Saf. 2000 Nov;23(5):429-448. Review.
[39] 温 忠 慧 , 欧 阳 钦 .4- 氨 基 水 杨 酸 治 疗 溃 疡 性 结 肠 炎 [J]. 中 华 内 科 杂志,1997,36(70):470-471. Wen Zhonghui, Ouyang Qin. 4-ASA in the Treatment of Ulcerative Colitis [ J ]. Chinese Journal of Internal Medicine,1997,36(70):470-471.
[40]刘军英,李玉凤,刑林山.4-氨基水杨酸局部治疗溃疡性结肠炎[J].临床消化杂志,1997,9(2):82.
[41]Daniel F,Seksik P,Cacheux W,et al.Tolerance of 4-aminosalicylic acid enemas in patients with inflammatory bowel disease and 5-aminosalicylic-induced actue pancreatitis.Inflamm Bowel Dis,2004 May;10(3):258-260.
[42]Beeken W,Howard D,Bigelow J,et al.Controlled trial of 4-ASA in ulcerative colitis.Dig Dis Sci,1997 Feb;42(2):354-358.
[43]Domenech E. Inflammatory bowel disease: current therapeutic options [J]. Digestion, 2006;73 Suppl 1:67-76.
[44]Kornbluth A, Sachar DB.Ulcerative colitis practice guidelines in adults(update): American College of Gastroenterology,Practice Parameters Committee[J]. Am J Gastroenterol,2004 Jul;99(7):1371-1385.
[45]Lakatos PL,Lakatos L.Ulcerative proctitis:a review of pharmacotherapy and management.Expert Opin Pharmacother,2008 Apr;9(5):741-749.
[46]Sood A,Midha V,Sood N,et al.A prospective,open-label trial assessing dexamethasone pulse therapy in moderate to severe ulcerative colitis[J].J Clin Gastroenterol,2002 Oct;35(4):328-331.
[47]Cunliffe RN,Scott BB.Monitoring for drug side-effects in inflammatory bowel disease[J].Aliment Pharmacol Ther,2002;16(4): 647-662.
[48]Gionchetti P,Rizzello F,Poggioli G,et al.Oral budesonide in the treatment of chronic refractory pouchitis.Aliment Pharmacol Ther,2007 May;25(10):1231-1236.
[49]Gionchetti P,D’Arienzo A,Rizzello F,et al.Topic treatment of distal active ulcerative colitis with beclomethasone dipropionate or mesalamine:a single-blind randomized controlled trial.J Clin Gastroenterol,2005 Apr;39(4):291-297.
[50]Katz JA.Treatment of inflammatory bowel disease with corticosteroids. Gastroenterol Clin North Am,2004 Jun;33(2):171-189.
[51]Haghighi DB,Lashner BA.Left sided ulcerative colitis.Gastroenterol Clin North Am, 2004 Jun;33(2):271-284.
[52]Okamura S,Aoki H,Ohashi S,et a1.Efficacy of cyclosporin with corticotrophin for refractory ulcerative colitis[J]. Hepatogastroentero1ogy,2003 Jan-Feb;50(49):91-94.
[53]Ouyang Q,Tandon R,Goh KL,et al.Management consensus of inflammatory bowel disease for the Asia-Pacific region[J].J Gastroenterol Hepatol,2006 Dec;21(12): 1772-1782..
[54]Cameron EA,Binnie JA,Balan K,et al.Oral prednisolone metasulphobenzoate in the treatment of active ulcerative colitis.Scand J Gastroenterol,2003 May;38(5):535-537.
[55]Durai D,Hawthorne AB.Review article:how and when to use ciclosporin in ulcerative colitis[J]. Aliment Pharmacol Ther,2005 Nov 15;22(10):907-916.
[56]Danese S,De la Rue SA,Gasbarrini A.Antibody to alpha4beta7 integrin for ulcerative colitis.N Engl J Med,2005 Sep15;353(11):1180-1181.
[57]王群英,陈村龙,孙勇,等.溃疡性结肠炎患者菌群分析结果的研究[J].中国微生态学杂志,2002,14(1): 31-32.
[58]辛光宾,李立新.地尔硫与环丙沙星联用治疗溃疡性结肠炎 16 例分析[J].辽宁医学杂志,2000,14(4):213.
[59]Ohkusa T,Nomura T,Terai T,et al.Effectiveness of antibiotic combination therapy in patients with active ulcerative colitis:A randomized,controlled pilot trial with long-term follow-up[J]. Scand J Gastroenterol,2005 Nov;40(11):1334-1342.
[60]Gionchetti P,Rizzello F,Morselli C,et al.Management of inflammatory bowel disease:does rifaximin offer any promise?Chemotherapy,2005;51 Suppl 1:96-102.
[61]Kozuch PL,Hanauer SB.Treatment of inflammatory bowel disease:a review of medical therapy.World J Gastroenterol,2008 Jan 21;14(3):354-377.
[62]Satror RB.Mechanisms of disease:pathogenesis of crohn’s disease and ulcerative colitis.Gastroenterol Hepatol,2006,3(7):390-406.
[63]Kato K,Mizuno S,Umesaki Y,et al.Randomized placebo-controlled trial assessing the effect of bifidobacteria-fermented milk on active ulcerative colitis.Aliment Pharmacol Ther,2004,20(10):1133-1141.
[64]Ishikawa H,Akedo I,Umesaki Y,et al.Randomized controlled trial of the effect of bifidobacteria-fermented milk on ulcerative colitis.J Am Coll Nutr,2003 Feb;22(1):56-63.
[65]Chapman TM,Plosker GL,Fiqqitt DP.Spotlight on VSL#3 probiotic mixture in chronic inflammatory bowel diseases.BioDrugs,2007;21(1):61-63.
[66]Bibiloni R,Fedorak RN,Tannack GW,et al.VSL#3 probiotic-mixture induces remis -sion in patients with active ulcerative colitis.Am J Gastroenterol, 2005 Jul;100(7): 1539- 1546.
[67]Chermesh I,Eliakim R.Probiotics and the gastrointestinal tract:Where are we in 2005?World J Gastroenterol,2006 Feb 14;12(6):853-857.
[68]Kruis W, Fric P, Pokrotnieks J, et al. Maintaining remission of ulcerative colitis with probiotic Escherichia coliNissle 1917 is as effective as with standard mesalazine[J].Gut,2004 Nov; 53(11):1617-1623.
[69]Famularo G, Mosca L, Minisola G, et al. Probiotic lactobacilli a new perspective for the treatment of inflammatory bowel disease[J].Curr Pharm Des, 2003;9(24): 1973-1980.
[70]Tursi A,Brandimarte G,Giorgetti GM,et al.Low-dose balsalazide plus a high-potencyprobiotic preparation is more effective than balsalazide alone or mesalazine in the treatment of acute mild-to-moderate ulcerative colitis.Med Sci Monit,2004,10(11):PI 126-131.
[71]Zocco MA,dal Verme LZ,Cremonini F,et al.Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitis.Aliment Pharmacol Ther,2006 Jun 1;23(11):1567-1574.
[72]Mimura T,Rizzello F,Helwig U,et al.Once daily high dose probiotic therapy (VSL#3) for maintaining remission in recurrent or refractory pouchitis.Gut,2004 Jan;53(1)108-114.
[73]Fedorak RN,Madsen KL.Probiotics and the management of inflammatory bowel disease.Inflamm Bowel Dis.2004 May;10(3):286-299.
[74]Tursi A,Brandimarte G,Giorqett GM,et al.Balsalazide and/or high-potency probiotic mixture(VSL#3)in maintaining remission after attack of acute,uncomplicated diverticulitis of the colon.Int J Colorectal Dis,2007 Sep;22(9):1103-1108.
[75]Rioux KP,Fedorak RN.Probiotics in the treatment of inflammatory bowel disease.J Clin Gastroenterol,2006,40(3):260-263.
[76]Shanahan F.Probiotics in inflammatory bowel disease-therapeutic rationale and role.Adv Dru Deliv Rev,2004 Apr 19;56(6):809-818.
[77]Ben-Arye E,Goldin E,Wengrower D,et al.Wheat grass juice in the treatment of active distal ulcerative colitis:a randomized double-blind placebo-controlled trial.Scand J Gastroenterol,2002 Apr;37(4):444-449.
[78]Langmead L,Dawson C,Hawkins C,et al.Antioxidant effects of herbal therapies used by patients with inflammatory bowel disease:an in vitro study.Aliment Pharmacol Ther,2002 Feb;16(2):197-205.
[79]吕永慧.炎症性肠病的中医治疗[J].中国实用内科杂志,2003, 19 (5): 457-459.
[80]张振书,周殿元.溃疡性结肠炎的内科治疗[J].胃肠病学,2004,9(4):251-254.
[81]宋良,张进峰,郜艳丽.中西医结合治疗慢性非特异性结肠炎 131 例[J].河南中医学院学报,2003,18(1):47-48.
[82]夏金荣,张少虹,杨杰.中西药联合灌肠治疗溃疡性结肠炎的疗效观察.临床消化病杂志,2002,14(1):19-21.
[83]苏娟萍,冯五金.肠必安灌肠治疗溃疡性结肠炎的临床研究[J].山西中医学院学报,2006,7(3):30-31.
[84] 朱 凤 玲 . 中 药 灌 肠 治 疗 慢 性 溃 疡 性 结 肠 炎 50 例 [J]. 实 用 中 医 内 科 杂志,2005,19(1):70-71.
[85]杜群,李红,王建华等.溃结灵对溃疡性结肠炎大鼠结肠粘膜 NF-κB p65 蛋白表达及血清 TNF-α含量的影响.广州中医药大学学报,2007,5(24):396-399.
[86]陈英群,马贵同,冯怡等.清肠泡腾栓对溃疡性结肠炎模型大鼠细胞因子的影响.中医杂志,2007,7(48):638-640.
[87]段永强,程畅和,成映霞等.痛泻二草方对溃疡性结肠炎模型大鼠血清IL-2含量及肠黏膜NO含量、NOS活性的影响.中国中医药信息杂志,2007,1(14):34-36.
[88]Papa A,Danese S,Gasbarrini G,et al.When can unfractionated heparin really be useful in the treatment of ulcerative colitis?Gastroenterology,2001 Apr;120(5):1306-1307.
[89]He G,Ouyang Q,Chen D,et al.The microvascular thrombi of colonic tissue in ulcerative colitis.Dig Dis Sci,2007 Sep;52(9):2236-2240.
[90]贺国斌.溃疡性结肠炎的血栓前状态与肝素治疗[J].国外医学#内科学分册,2000,27(6):238-241.
[91]贺国斌,欧阳钦.肝素治疗右旋葡聚糖硫酸钠诱导小鼠结肠炎的疗效观察[J].中华消化杂志,2002,22(9):546-549.
[92]Hostutler RA,Luria BJ,Johnson SE,et al.Antibiotic-responsive histiocytic ulcerative colitis in 9 dogs.J Vet Intern Med,2004,18(4):499-504.
[93]Zezos P,Papaioannou G,Nikolaids N,et al.Low-molecular-weight heparin(enoxaparin) as adjuvant therapy in the treatment of active ulcerative colitis:a randomized,controlled,comparative study.Aliment Pharmacol Ther,2006 May;23(10):1443-1453.
[94]Shen J,Ran ZH,Tong JL,et al.Meta-analysis:The utility and safety of heparin in the treatment of active ulcerative colitis.Aliment Pharmacol Ther,2007 Sep;26(5):653-663.
[95]Dotan I,Hallak A,Arber N,et al.Low-dose low-molecular weight heparin(enoxaparin)is effective as adjuvant treatment in active ulcerative colitis:an open trial.Digestive Disease and Sciences,2001 Oct;46(10):2239-2244.
[96]徐德亮,穆平,沙士义等.溃疡性结肠炎血液流变学及抗凝治疗的临床研究.胃肠病学和肝病学杂志,2005,4(14):413
[97] 江学良 , 刘涛 . 肝素治疗顽固性溃疡性结肠炎一例 [J]. 世界华人消化杂志,1999,7(8):694.
[98]McGilligan VE,Wallace JM,Heavey PM,et al.Hypothesis about mechanisms through which nicotine might exert its effect on the interdependence of inflammation and gut barrier function in ulcerative colitis.Inflamm Bowel Dis,2007 Jan;13(1):108-115.
[99]Sandborn WJ,Tremaine WJ,Offord KP,et al.Transdermal nicotine for mildly to moderately active ulcerative colitis:a randomized,double blind,placebo-controlled trial.Ann Intern Med,1997 Mar 1;126(5):364-371.
[100]Ingram JR,Rhodes J,Evans BK,et al.Preliminary observations of oral nicotine therapy for inflammatory bowel disease:an open-label phase Ⅰ - Ⅱ study of tolerance.Inflamm Bowel Dis,2005 Dec;11(12):1092-1096.
[101]Hanauer SB.Review article:the long-term management of ulcerative colitis.Aliment Pharmacol Ther,2004 Oct;20(Suppl 4):97-101
[102]Green JT,Richardson C,Marshall RW,et al.Nitric oxide mediates a therapeutic effect of nicotine in ulcerative colitis[J].Aliment Pharmacol Ther,2000 Nov;14(11):1429- 1434.
[103]Bartnik W.Inflammatory bowel disease Polish contribution [J].J Physiol Pharmacol,2003,54(Suppl 3):205-210.
[104]Fuss IJ.Cytokine network in inflammatory bowel disease.Curr Drug Targets Inflamm Allergy.2003 Jun;2(2):101-112.
[105]Braegger CP,Macdonald TT.Immune mechanisms in chronic inflammatory bowel disease.Ann Allergy,1994 Feb;72(2):135-141.
[106]Bhan AK,Mizoguchi E,Smith RN,et al.Colitis in transgenic and knockout animals as models of human inflammatory bowel disease.Immunol Rev,1999 Jun;169:195–207.
[107]Hanauer SB.Inflammatory bowel disease:epidemiology,pathogenesis,and therapeutic opportunities.Inflamm Bowel Dis,2006 Jan;12 Suppl 1:S3-9.
[108]丁伟群,林庚金,徐三荣等.溃疡性结肠炎发病中白介素水平的变化[J].复旦学报(医学科学版),2001,28(4):330-333.
[109]Kelly-Welch AE, Hanson EM, Boothby MR,et al.Interleukin-4 and interleukin-13 signaling connections maps.Science,2003 Jun 6;300(5625):1527-1528.
[110]Carol M,Lambrechts A,Van Gossum A,et al.Spontaneous secretion of interferon gamma and interleukin 4 by human intraepithelial and lamina propria gut lymphocytes[J].Gut,1998 May;42(5):643-649.
[111]Elson CO,Beagley KW,Sharmanov AT,et al.Hapten-induced model of murine inflammatory bowel disease.Mucosal immune responses and protection by tolerance.J Immunol,1996 Sep 1;157(5):2174–2185.
[112]Nielsen OH,Koppen T,Rudiger N,et al.Involvement of interleukin-4 and-10 in inflammatory bowel disease.Dig Dis Sci,1996 Sep;41(9):1786-1793.
[113]Hogaboam CM,Vallance BA,Kumar A,et al.Therapeutic effects of interleukin-4 gene transfer in experimental inflammatory bowel disease.J Clin Invest,1997 Dec 1;100(11):2766-2776.
[114]Macdonald TT. Viral vectors expressing immunoregulatory cytokines to treat inflammatory bowel disease[J].Gut,1998,42(4):460-461.
[115]West GA,Matsuura T,Levine AD,et al.Interleukin-4 in inflammatory bowel disease and mucosal immune reactivity[J].Gastroenterology,1996,110(6):1683-1695.
[116]Mittal RD,Bid HK,Ghoshal UC.IL-1 receptor antagonist (IL-1Ra) gene polymorphism in patients with inflammatory bowel disease in India. Scand J Gastroenterol. 2005 Jul;40(7):827-831.
[117]Rogy MA,Beinhauer BG,Reinisch W,et al.Transfer of interleukin-4 and Interleukin-10 in patients with severe inflammatory bowel disease of the rectum.Hum Gene Ther,2000 Aug 10;11(12):1731-1741.
[118]Blumberg RS,Saubermann LJ,Strober W.Animal models of mucosal inflammation and their relation to human inflammatory bowel disease.Crurr Opin Immunol,1999Dec;11(6):648-656.
[119]Sawa Y, Oshitani N, Adachi K,et al. Comprehensive analysis of intestinal cytokine messenger RNA profile by real-time quantitative polymerase chain reaction in patients with inflammatory bowel disease.Int J Mol Med,2003;11(2):175-179.
[120]Inoue S, Matsumoto T, Iida M, et al. Characterization of cytokine expression in the rectal mucosa of ulcerative colitis: correlationwith disease activity. Am J Gastroenterol, 1999 Sep;94(9):2441-2446.
[121]Erdman S E,Rao V P,Poutahidis T,et al.CD4( +)CD25(+) regulatory lymphocytes require interleukin-10 to interrupt colon carcinogenesis in mice[J].Cancer Res,2003 Sep 15;63(18):6042-6050.
[122]Rennick DM,Fort MM . Lessons from genetically engineered animal models.XII.IL-10-deficient (IL-10-/-) mice and intestinal inflammation[J].Am J Physiol Gastrointest Liver Physiol,2000,278(6):G 829-833.
[123]Latinne D,Fiasse R.New insights into the cellular immunology of the intestine in relation to the pathophysiology of inflammatory bowel diseases.Acta Gastroenterol Belg,2006 Oct-Dec;69(4):393-405.
[124]Joel V,Weinstock,Arthur Blum,et al.Substance P Regulates Th1-Type Colitis in IL-10 Knockout Mice[J].J Immunol,2003;171(2):3762-3767.
[125]Gasche C,Bakos S,Dejaco C,et al.IL-10 secretion and sensitivity in normal human intestine and inflammatory bowel disease.J Clin Immunol,2000 Sep;20(5):362-370.
[126]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 Jul;153(1):121-130.
[127] Mitsuyama K,Tomiyasu N,Takaki K,et al.Interleukin-10 in the pathophysiology of inflammatory bowel disease:increased serum concentrations during the recovery phase.Mediators Inflamm,2006;2006(6):26875.
[128]Melgar S,Yeung MM,Bas A,et al.Over-expression of interleukin 10 in mucosal T cells of patients with active ulcerative colitis. Clin Exp Immunol,2003 Oct;134(1): 127-137.
[129]Driessler F,Venstrom K,Sabat R,et al.Molecular mechanisms of interleukin-10-mediated inhibition of NF-kappa B activity:a role for p50.Clin Exp Immunol,2004 Jan;135(1):64-73.
[130]Lindsay JO,CiesielskiC J,ScheininT,et al.Local delivery of adenoviral vectors encoding murine interleukin-10 induces colonic interleukin-10 production and is therapeutic for murine colitis[J].Gut,2003 Jul;52(7):981-987.
[131]Lindsay JO,Sandison A,Cohen P,et al.IL-10 gene therapy is therapeutic for dextran sodium sulfate induced murine colitis[J].DigDis Sci,2004 Aug;49(7-8):1327-1334.
[132]Schreiber S,Fedorak RN,Nielsen OH,et al.Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn’s disease. Crohn’s Disease IL-10 Cooperative Study Group[J].Gastroenterology,2000;119(6):1461-1472.
[133]Bickston SJ,Cominelli F.Recombinant interleukin 10 for the treatment of active Crohn’s disease:lessons in biologic therapy[J].Gastroenterology,2000 Dec;119(6): 1781- 1783.
[134]Fedorak RN,Gangl A,Elson CO,et al.Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn’s disease.The Interleukin 10 Inflammatory Bowel Disease Cooperative Study Group [J].Gastroenterology,2000;119(6):1473-1482.
[135]Schreiber S,Hernig T,Thiele HG,et al.Immmunoregulatory role of interleukin-10 in patients with inflammatory bowel disease[J].Gastroenterology,1995 May;108(5):1434-1444.
[136]Niedergang F,Didierlaurent A,Kraehenbuhl JP,et al.Dendritic cells:the host Achille’s heel for mucosal pathogens?Trends Microbiol,2004 Feb;12(2):79-88.
[137]Sandborn WJ,Targan SR[J].Biologic therapy of inflammatory bowel disease.Gastroenterology,2002 May;122(6):1592-1608.
[138] 吕 农 华 , 罗 玲 玉 . 白 细 胞 介 素 与 炎 症 性 肠 病 [J]. 中 国 实 用 内 科 杂志.2007,18(27):1437-1439.
[139]Nikolaus S,Rutgeerts P,Fedorak R,et al.Interferon beta-1a in ulcerative colitis: a placebo controlled,randomised,dose escalating study[J].Gut,2003 Sep;52(9):1286-1290.
[140]Fuss IJ,Neurath M,Boirivant M,et al.Disparate CD+4 lamina propria(LP)lymphokine secretion profiles in inflammatory bowel disease.Crohn’s disease LP cells manifest increased Secretion of IFN-gamma,whereas ulcerative colitis LP cells manifest increased secretion of IL-5[J].J Immunol,1996 Aug;157(3):1261-1270.
[141]Schlottmann K,Wachs F P,Grossmann J,et al.Interferon gamma downregulates IL-8 production in primary human colonic epithelial cells without induction of apoptosis[J].Int J Colorectal Dis,2004 Sep;19(5):421-429.
[142]Sventoraitte J,Zvirbliene A,Kiudelis G,et al.Immune system alterations in patients with inflammatory bowel disease during remission.Medicina(Kaunas), 2008;44(1):27-33.
[143]Simpson SJ,Hollander GA,Mizoguchi E,et al.Expression of pro-inflammatory cytokines by TCR alpha beta+ and TCR gamma delta+T cells in an experimental model of colitis.Eur J Immunol,1997 Jan;27(1):17-25.
[144]Ito R,Shin-Ya M,Kishida T,et al.Interferon-gamma is causatively involved in experimental inflammatory bowel disease in mice.Clin Exp Immunol,2006 Nov;146(2):330-338.
[145]Mizoguchi A,Mizoguchi E,Chiba C,et al.Cytokine imbalance and autoantibody production in T cell receptor-alpha mutant mice with inflammatory bowel disease.J Exp Med,1996;183(3):847-856.
[146]Takahashi I,Iijima H,Katashima R,et al.Clonal expansion of CD4+TCRbetabeta+T cells in TCR alpha-chain-deficient mice by gut-derived antigens.J Immunol,1999;162(3):1843-1850.
[147]Waidmann M,Allemand Y, Lehmann J,et al.Microflora reactive IL-10 producing regulatory T cells are present in the colon of IL-2 deficient mice but lack efficacious inhibition of IFN-gamma and TNF-alpha production[J].Gut,2002 Feb; 50(2): 170-179.
[148]Malek TR.The main function of IL-2 is to promote the development of T regulatorycells[J].J Leukoc Biol,2003 Dec;74(6):961-965.
[149]Kullberg MC,Ward JM,Gorelick PL,et al.Helicobacter hepaticus triggers colitis in specific-pathogen-free interleukin-10 ( IL-10)-deficientmice through an IL-12-and gamma interferon-depend-entmechanism[J].Infect Immun,1998 Nov;66(11): 5157- 5166.
[150]Elson CO,Cong Y,McCracken VJ,et al.Experimental models of inflammatory bowel disease reveal innate, adaptive, and regulatory mechanisms of host dialogue with the microbiota[J].Immun Rev,2005 Aug;206:260-276.
[151]Ohman L, Franzen L,Rudolph U,et al.Regression of Peyers'patches in Gai2 deficient mice prior to colitis is associated with reduced expression of Bcl-2 and increased apoptosis[J].Gut,2002 Sep;51(3):392-397.
[152]Dieleman LA,Goerres MS,Arends A,et al.Lactobacihhus GG prevents recurrence of colitis inHLA-B27 transgenic rats after antibiotic treatment[J].Gut,2003 Mar;52(3): 370-376.
[153]Wirtz S,Finotto S,Kanzler S,et al.Cutting edge: chronic intestinal inflammation in STAT-4 transgenic mice:characterization of disease and adoptive transfer by TNF-plus IFN-gamma-producing CD4+T cells that respond to bacterial antigens[J].J Immunol,1999 Feb;162(4):1884-1888.
[154]Madara JL,Podolsky DK,King NW,et al.Characterization of spontaneous colitis in cotton-top tamarins(Saguinus oedipus)and its response to sulfasalazine[J].Gastroenterology, 1985 Jan;88(1 Pt 1):13-19.
[155]Sundberg JP,Elson CO,Bedigian H,et al.Spontaneous,heritable colitis in a new substrain of C3H/HeJ mice.Gastroenterology,1994 Dec,107(6):1726-1735.
[156]Matsumoto S,Okabe Y,Setoyama H,et al.Inflammatory bowel disease-like enteritis and caecitis in a senescence accelerated mouse P1/Yit strain.Gut,1998;43(1):71-78.
[157]Aranda R,Sydora BC,McAllister PL,et al.Analysis of intestinal lymphocytes in mouse colitis mediated by transfer of CD4+,CD45RBhigh T cells to SCID recipients.J Immunol,1997;158(7):3464-3473.
[158]Wirtz S,Neufert C,Weigmann B,et al. Chemically induced mouse models ofintestinal inflammation.Nat Protoc,2007;2(3):541-546.
[159]Neurath MF,Fuss I,Kelsall BL,et al.Antibodies to interleukin 12 abrogate established experimental colitis in mice[J].J Exp Med,1995 Nov 1;182(5):1281-1290.
[160]Bailón E, Camuesco D,Nieto A,et al.The intestinal anti-inflammatory effects of the novel agent UR-1505 in the TNBS model of rat colitis are mediated by T-lymphocyte inhibition.Biochem Pharmacol,2007 Nov 15;74(10)1496-1506.
[161]Okayasu I,Hatakeyama S,Yamada M,et al.A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice[J].Gastroenterology,1990 Mar;98(3):694-702.
[162]Sivakumar PV,Westrich GM, Kanaly S,et al.Interleukin 18 is a primary mediator of the inflammation associated with dextran sulphate sodium induced colitis: blocking interleukin 18 attenuates intestinal damage[J].Gut,2002 Jun;50(6):812-820.
[163]Cooper HS,Murthy S,Kido K,et al.Dysplasia and cancer in the dextran sulfate sodium mouse colitis model.Relevance to colitis-associated neoplasia in the human:a study of histopathology,B-catenin and p53 expression and the role of inflammation.Carcinogenesis,2000,21(4):757-768.
[164]Guo SM,Tong HB,Bai LS,et al.Effect of traditional Chinese medicinal enemas on ulcerative colitis of rats[ J].World J Gastroenterol,2004 Jul 1;10(13):1914-1917.
[165]Glick ME,Falchuk ZM.Dinitrochlorobenzene-induced colitis in the guinea-pig:studies of colonic lamina propria lymphocytes[J].Gut,1981 Feb;22(2): 120-125.
[166]Boirivant M,Fuss IJ,Chu A,et al.Oxazolone colitis:a murine model of T helper cell type 2 colitis treatable with antibodies to interleukin 4[J].J Exp Med.1998 Nov;188(10):1929–1939.
[167]Kojima R,Kuroda S,Ohkishi T, et al.Oxazolone-induced colitis in BALB/C Mice: a new method to evaluate the efficacy of therapeutic agents for ulcerative colitis[J].J Pharmacol Sci,2004 Nov;96(3):307-313.
[168]Heller F,Fuss IJ,Nieuwenhuis EE,et al.Oxazolone colitis,a Th2 colitis model resembling ulcerative colitis,is mediated by IL-13-producing NK-T cells[J].Immunity,2002 Nov,17(5): 629-638.
[169]Thomson JA,Troutt AB,Kelso A.Contact sensitization to oxazolone:involvement of both interferon-gamma and interleukin-4 in oxazolone-specific Ig and T-cell respo- nses.Immunology,1993 Feb;78(2):185-192.
[170]Sun X,Somada S,Shibata K,el al.A critical role of CD30 ligand/CD30 in controlling inflammatory bowel diseases in mice[J].Gastroenterology,2008 Feb;134(2):447-458.
[171]Arseneau KO,Pizarro TT,Cominelli F.Discovering the cause of inflammatory bowel disease:lessons from animal models.Curr Opin Gastroenterol,2000 Jul;16(4):310-317.
[172]Philippe D,Dubuquoy L,Groux H,et al.Anti-inflammatory properties of the mu opioid receptor support its use in the treatment of colon inflammation[J].J Clin Invest,2003 May;111(9):1329-1338.
[173]Luk HH,Ko JK,Fung HS,et al.Delineation of the protective action of zinc sulfate on ulcerative colitis in rats.Eur J Pharmacol,2002 May 17;443(1-3):197-204.
[174]韩英,村田有志,伊东重豪等.长期应用尼古丁对噁唑酮诱导的实验性小鼠肠炎模型的影响及其机制探讨.中华消化杂志,2001;21(8):473-476.
[175]Fabia R,Ar’Rajab A,Johansson ML,et al.The effect of exogenous administration of Lactobacillus reuteri R2LC and oat fiber on acetic acid-induced colitis in the rat.Scand J Gastroenterol,1993 Feb;28(2):155-162.
[176]Strober W,Fuss IJ,Blumberg RS.The immunology of mucosal models of inflammation.Annu Rev Immunol,2002;20:495–549.
[177]Neurath MF,Finotto S,Glimcher LH.The role of Th1/Th2 polarization in mucosal immunity.Nat Med,2002 Jun;8(6):567-573.
[178] Bamias G,Sugawara K,Pagnini C,et al.The Th1 immune pathway as a therapeutic target in Crohn's disease.Curr Opin Investig Drugs,2003 Nov;4(11):1279-1286.
[179] Okazawa A,Kanai T,Watanabe M,et al.Th1-mediated intestinal inflammation in Crohn's disease may be induced by activation of lamina propria lymphocytes through synergistic stimulation of interleukin-12 and interleukin-18 without T cell receptor engagement.Am J Gastroenterol,2002 Dec;97(12):3108-3117.
[180]Mizoguchi A,Mizoguchi E,Saubermann LJ,et al.Limited CD4 T-cell diversityassociated with colitis in T-cell receptor alpha mutant mice requires a T helper 2 environment.Gastroenterology,2000 Oct;119(4):983-995.
[181]Van Damme N,De Keyser F,Demetter P,et al.The proportion of Th1 cells,which prevail in gut mucosa,is decreased in inflammatory bowel syndrome.Clin Exp Immunol,2001 Sep;125(3):383-390.
[182]Salem ML.Estrogen,a double-edged sword:modulation of TH1-and TH2-mediated inflammations by differential regulation of TH1/TH2 cytokine production.Curr Drug Targets Inflamm Allergy,2004 Mar;3(1):97-104.
[183]Boirivant M,Strober W,Fuss IJ.Regulatory cells induced by feeding TNP-haptenated colonic protein cross-protect mice from colitis induced by an unrelated hapten.Inflamm Bowel Dis,2005 Jan;11(1):48-55.
[184]Neurath M,Fuss I,Strober W.TNBS-colitis.Int Rev Immunol,2000;19(1):51-62.
[185]Cottrez F,Hurst SD,Coffman RL,et al.T regulatory cells 1 inhibit a Th2-specific response in vivo.J Immunol,2000 Nov 1;165(9):4848-4853.
[186]中华医学会消化病学分会.对炎症性肠病诊断治疗规范的建议[J].中华消化杂志,2001;21(4):236-239.
[187]Truelove SC,Richards WC.Biopsy studies in ulcerative colitis[J]. Br Med J,1956 Jun 9;1(4979):1315-1318.
[188]中国炎症性肠病协作组.3100 例溃疡性结肠炎住院病例回顾分析.中华消化杂志,2006,26(6):368-372.
[189]Jani N, Regueiro MD.Medical therapy of ulcerative colitis[J].Gastroenterol Clin North Am,2002 Mar;31(1):147-166.
[190]陈劲勇,周志光,王跃平.柳氮磺吡啶加中药与单用柳氮磺吡啶在溃疡性结肠炎中的疗效比较[J].中国新药与临床杂志,2003,22(5):287-288.
[191]Hanauer SB.Update on the etiology, pathogenesis and diagnosis of ulcerative colitis.Nat Clin Pract Gastroenterol Hepatol,2004 Nov;1(1):26-31.Review.
[192]庞艳华,郑长清,王轶淳等.IL-4 和 IL-13 在溃疡性结肠炎中的表达.胃肠病学和肝病学杂志,2005,4(14):410-412.
[193]Kimura I,Kawasaki M,Nagahama S,et al.Determination of the active moiety ofBX661A,a new therapentic agent for ulcerative colitis,by studying its therapeutic effects on ulcerative colitis induced by dextran sulfate sodium in rats[J].Arznei mittelforschung,1998 Nov;48(11):1091-1096.
[194] 木 村 伊 佐 美 , 永 滨 忍 , 川 崎 真 规 . 巴 柳 氮 的 药 理 学 研 究 [J]. 日 药 理志,1997,109(2):85-94.
[195]McNeil HP, Simpson RJ,Chesterman CN, et al.Antiphospholipid antibodies are directed against a complex antigen that includes a lipid binding inhibitor of coagulation β2-glycoproteinⅠ (apolipoprotein H)[J].Proc Natl Acad Sci USA,1990;87(11): 4120-4124.
[196]Galli M, Comfuius P,Maassen C, et al.Anticardiolipin antibodies(ACA) directed not to cardiolipin but to a plasma cofactor[ J].Lancet,1990;335(8705):1544-1547.
[197]Davies ML,Young SP,Welsh K,et al.Immune responses to native beta(2)-glycoprotein I in patients with systemic lupus erythematosus and the antiphospholipid syndrome.Rheumatology(Oxford),2002 Apr;41(4):395-400.
[198]Kalt M,Gertner E.Antibodies to beta 2-glycoprotein I and cardiolipin with symptoms suggestive of systemic lupus erythematosus in parvovirus B19 infection.J Rheumatol,2001 Oct;28(10):2335-2336.
[199]Gerorge J,Blank M,Lery Y,et al.Differential effects of anti-beta2-glycoprotein I antibodies on endothelial cells and on the manifestations of experimental antiphospholipid syndrome.Circulation,1998 Mar;97(9):900-906.
[200]Arvieux J,Roussel B, Jacob MC, et al.Measurement of anti-phospholipid antibodies by ELISA using beta 2-glycoproteinⅠ as an antigen[J].J Immunol Methods,1991 Oct 25;143(2):223-229.
[201]Bondanza A,Sabbadini MG,Pellegatta F,et al.Anti-beta2-glycoprotein I antibodies prevent the De-activation of platelets and sustain their phagocytic clearance.J Autoimmun,2000 Dec;15(4):469-477.
[202]Meroni PL, Raschi E, Testoni C, et al.Statins prevent endothelial cell activation induced by antiphospholipid (anti-beta2-glycoproteinⅠ ) antibodies:effect on the proadhesive and proinflammatory phenotype[J].Arthritis Rheum,2001 Dec,44(12):2870-2878.
[203]Delpapa N, Sheng YH, Raschi E, et al.Human beta 2-glycoproteinⅠ binds to endothelial cells through a cluster of lysine resiclues that are critical for anionic phospholipid binding and offers epitopes for anti-beta 2-glycoproteinⅠantibodies[ J].J Immunol,1998 Jun;160(11):5572-5578.
[204]Campieri M,Adamo S,Valpiani D,et al.Oral beclometasone dipropionate in the treatment of extensive and left-sided active ulcerative colitis:a multicentre randomised study.Aliment Pharmacol Ther,2003 Jun 15;17(12):1471-1480.
[205]Graef V, Baggenstoss AH, Sauer WG, et al.Venous thrombosis occurring in nonspe -cific ulcerative colitis: a necropsy study[ J].Arch Intern Med,1966;117(2):377-382.
[206]Webberley MJ, Hart MT, Melikian V. Thromboembolism in inflammatory bowel Disease: role of platelets.Gut,1993 Feb;34(2):247-251.
[207]Lam A,Borda IT,Inwood MJ,et al. Coagulation studies in ulcerative colitis and Crohn's disease.Gastroenterology,1975 Feb;68(2):245-251.
[208]Papa A, Danese S, Gasbarrini A, Gasbarrini G. Review article: potential therapeutic applications and mechanisms of action of heparin in inflammatory bowel disease. Aliment Pharmacol Ther,2000 Nov;14(11):1403-1409.
[209]张连峰,田曙光,王国新.溃疡性结肠炎患者血小板功能状态的研究[J].中国实用内科杂志, 2000, 20(2): 98-99.
[210]吴曦,刘新光,田宇,等.炎症性肠病患者的临床表现(附 201 例临床分析) [ J].中国实用内科杂志, 2006, 26 (3): 190 -193.
[211]Dong WG, Liu SP, Zhu HH, et a.l Abnormal function of platelets and role of angelica sinensis in patients with ulcerative colitis[J].World J Gastroenterol,2004 Feb 15;10(4): 606-609.
[212]Singh AK.Immunopathogenesis of the antiphospholipid antibody syndrome: an update[J].Curr Opin Nephrol Hypertens,2001 May;10(3):355-358.
[2]Eaden J,Abrams K,Ekbom A,et al.Colorectal cancer prevention in ulcerative colitis:a case-control study.Aliment Pharmacol Ther,2000 Feb;14(2):145-153.
[3]Russel MG.Changes in the incidence of inflammatory bowel disease:what does it mean?Eur J Intern Med,2000 Aug;11(4):191-196.
[4]Orchard TR,Chua CN,Ahmad T,et al.Uveitis and erythema no-dosum in inflammatory bowel disease:clinical features and the role of HLA genes.Gastroenterology,2002 Sep;123(3):714-718.
[5]Ghosh S, Shand A, Ferguson A. Ulcerative colitis. Br Med J,2000 Apr 22;320(7242):1119-1123.
[6]Ardizzone S, Bianchi Porro G.Comparative tolerability of therapies for ulcerative colitis[J].Drug Saf,2002;25(8):561-582.
[7]Sandborn WJ.Oral 5-ASA Therapy in Ulcerative Colitis:What are the Implications of the New Formulations?J Clin Gastroenterol,2008 Apr;42(4):338-344.
[8]Farrell RJ. Peppercorn MA. Ulcerative colitis.Lancet,2002 Jan 26;359(9303):331-340.
[9]Xu CT, Meng SY, Pan BR. Drug therapy for ulcerative colitis.World J Gastroentero1,2004 Aug;10(16):2311-2317.
[10] 梁 毅 超 , 卿 三 华 . 溃 疡 性 结 肠 炎 的 外 科 治 疗 指 南 . 世 界 华 人 消 化 杂志,2006,14(21):2130-2134.
[11]Campbell DE, Berglindh T.Pharmacology of Olsalazine[J].Scand J Gastroenteol Suppl,1988;148:7-12.
[12]Wadorth AN,Fitton A.Olsalazine.A review of its pharmaco dynamic and pharmacokinetic properties and therapeutic potential in inflammatory bowel disease[J]. Drugs,1991Apr;41(4):647-664.
[13]Zhong YQ,Huang HR,Zhu ZH,et al.Effects of sulfasalazine on biopsy mucosalpathologies and histological grading of patients with active ulcerative colitis.World J Gastroenterol,2005 Jul;11(28):4435-4438.
[14]Chen QK,Yuan SZ,Wen ZF,et al.Characteristics and therapeutic efficacy of sulfasalazine in patients with mildly and moderately active ulcerative colitis.World J Gastroenterol,2005 Apr 28;11(16):2462-2466.
[15]Kamm MA.Review article:maintenance of remission in ulcerative colitis[J].Aliment Pharmacol Ther,2002 Jul;16 (Suppl4):21-24.
[16]胡伏莲,林庚金.美沙拉嗪治疗炎症性肠病的疗效及安全性-全国多中心临床研究[J].中国新药杂志,2001,10(3):201-203.
[17]Swaminath A,Kornbluth A.Optimizing drug therapy in inflammatory bowel disease.Curr Gastroenterol Rep,2007 Dec;9(6):513-520.
[18]Hanauer SB,Sandborn WJ,Kornbluth A,et al.Delayed-release oral mesalamine at4. 8 g/day (800 mg tablet) for the treatment of moderately active ulcerative colitis:the ASCEND II trial[J].Am J Gastroenterol,2005 Nov;100(11):2478-2485.
[19]Marteau P,Probert CS,Lindgren S,et a1.Combined oral and enema treatment with Pentasa(mesalazine) is superior to oral therapy alone in patients with extensive mild/moderate active ulcerative colitis: a randomised,double blind,placebo controlled study[J].Gut,2005 Jul;54(7):960-965.
[20]Gisbert JP,Gomollon F,Mate J,et al.Role of 5-aminosalicylicacid(5-ASA)in treatment of inflammatory bowel disease:a systematic review.Dig Dis Sci,2002 Mar;47(3):471-488.
[21]Frandsen NE,Saugmann S,Marcussen N.Acute interstitial nephritis associated with the use of mesalazine in inflammatory bowel disease.Nephron,2002 Sep;92(1):200-202
[22]Malchow H.A new mesalazine foam enema compared with a standard liquid enema in patients with active distal ulcerative colitis.Aliment Pharmacol Ther,2002 Mar;16(3):415-423.
[23]Hanauer SB.Medical therapy for ulcerative colitis 2004. Gastroenterol,2004 May; 126(6):1582-1592.
[24]Mahkam M.New pH-sensitive glycopolymers for colon-specific drug delivery.Drug Deliv,2007 Mar;14(3):147-153.
[25]蔡建庭,吴林峰,杜勤,等,奥沙拉秦钠胶囊和柳氮磺吡啶片治疗溃疡性结肠炎的随机对照研究[J].中华消化杂志,2001,21(10):593~595. Cai Jianting, Wu Linfeng, Du Qin,et al. Olaslazine Versus Sulfasalazine in the Treatment of Ulcerative Colitis: Randomized Controlled Clinical Trial[J]. Chinese Journal Digest,2001,21(10):593~595.
[26]Kruis W,Brandes JW,Schreiber S,et al.Olsalazine versus mesalazine in the treatment of mild to moderate ulcerative colitis.Aliment Pharmacol Ther,1998,12(8): 7607-7615.
[27]Prakash A,Markham A.Oral delayed-release mesalazine:a review of its use in ulcerative colitis and Crohn′s disease.Drugs,1999 Mar;57(3):383-408.
[28]Singer Mv,Schmausser H,Sch?nfeld G.Efficacy and tolerability of olsalazine (dipentum) in the treatment of patients with ulcerative colitis--results of a field study.Hepatogastroenterology,2006 May-Jun;53(69):317-321.
[29]Knoll U, Strauhs P, Schusser G,et al.Study of the plasma pharmacokinetics and faecal excretion of the prodrug olsalazine and it metabolites after oral administration to horses[J].J Vet Pharmaco Ther, 2002 Apr;25(2):135-143.
[30]Sandborn WJ,Hanauer SB.Systematic review:the pharmacokinetic profiles of oral mesalazine formulations and mesalazine pro-drugs used in the management of ulcerative colitis.Aliment Pharmacol Ther,2003 Jan;17(1):29-42.
[31]Stoa-Birketvedt G,Florholmen J.The systemic load and efficient delivery of active 5-aminosalicylic acid in patients with ulcerative colitis on treatment with olsalazine or mesalazine.Aliment Pharmacol Ther,1999;13(3):357-361.
[32]Kles KA,Vavricka SR,Turner JR,et al.Comparative analysis of the in vitro prosecretory effects of balsalazide,sulfasalazine,olsalazine,and mesalamine in rabbit distal ileum.Inflamm Bowel Dis,2005 Mar;11(3):253-257.
[33]Kornbluth A,Sachar DB. Ulcerative colitis.Am J Gastroenterol 1997;92(2):204-211.
[34]Ragunath K,Williams JG.Review article:balsalazide therapy in ulcerativecolitis[J].Aliment Pharmacol Ther,2001 Oct;15(10):1549-1554.
[35]王海鸥,韩伟,朱庆.巴柳氮钠研究情况综述.实用医技杂志,2003,10(5):531-533.
[36]Levine DS, Riff DS, Pruitt R,et al.A randomized,double blind,dose-response comparison of balsalazide (6.75 g), balsalazide (2.25 g), and mesalamine (2.4 g) in the treatment of active, mild-to-moderate ulcerative colitis.Am J Gastroenterol,2002 Jun;97(6):1398-1407.
[37]Mansfield JC, Giaffer MH, Cann PA,et al. A double-blind comparison of balsalazide, 6.75 g, and sulfasalazine, 3 g, as sole therapy in the management of ulcerative colitis.Aliment Pharmacol Ther. 2002 Jan;16(1):69-77.
[38]Stein RB,Hanauer SB.Comparative tolerability of treatments for inflammatory bowel disease.Drug Saf. 2000 Nov;23(5):429-448. Review.
[39] 温 忠 慧 , 欧 阳 钦 .4- 氨 基 水 杨 酸 治 疗 溃 疡 性 结 肠 炎 [J]. 中 华 内 科 杂志,1997,36(70):470-471. Wen Zhonghui, Ouyang Qin. 4-ASA in the Treatment of Ulcerative Colitis [ J ]. Chinese Journal of Internal Medicine,1997,36(70):470-471.
[40]刘军英,李玉凤,刑林山.4-氨基水杨酸局部治疗溃疡性结肠炎[J].临床消化杂志,1997,9(2):82.
[41]Daniel F,Seksik P,Cacheux W,et al.Tolerance of 4-aminosalicylic acid enemas in patients with inflammatory bowel disease and 5-aminosalicylic-induced actue pancreatitis.Inflamm Bowel Dis,2004 May;10(3):258-260.
[42]Beeken W,Howard D,Bigelow J,et al.Controlled trial of 4-ASA in ulcerative colitis.Dig Dis Sci,1997 Feb;42(2):354-358.
[43]Domenech E. Inflammatory bowel disease: current therapeutic options [J]. Digestion, 2006;73 Suppl 1:67-76.
[44]Kornbluth A, Sachar DB.Ulcerative colitis practice guidelines in adults(update): American College of Gastroenterology,Practice Parameters Committee[J]. Am J Gastroenterol,2004 Jul;99(7):1371-1385.
[45]Lakatos PL,Lakatos L.Ulcerative proctitis:a review of pharmacotherapy and management.Expert Opin Pharmacother,2008 Apr;9(5):741-749.
[46]Sood A,Midha V,Sood N,et al.A prospective,open-label trial assessing dexamethasone pulse therapy in moderate to severe ulcerative colitis[J].J Clin Gastroenterol,2002 Oct;35(4):328-331.
[47]Cunliffe RN,Scott BB.Monitoring for drug side-effects in inflammatory bowel disease[J].Aliment Pharmacol Ther,2002;16(4): 647-662.
[48]Gionchetti P,Rizzello F,Poggioli G,et al.Oral budesonide in the treatment of chronic refractory pouchitis.Aliment Pharmacol Ther,2007 May;25(10):1231-1236.
[49]Gionchetti P,D’Arienzo A,Rizzello F,et al.Topic treatment of distal active ulcerative colitis with beclomethasone dipropionate or mesalamine:a single-blind randomized controlled trial.J Clin Gastroenterol,2005 Apr;39(4):291-297.
[50]Katz JA.Treatment of inflammatory bowel disease with corticosteroids. Gastroenterol Clin North Am,2004 Jun;33(2):171-189.
[51]Haghighi DB,Lashner BA.Left sided ulcerative colitis.Gastroenterol Clin North Am, 2004 Jun;33(2):271-284.
[52]Okamura S,Aoki H,Ohashi S,et a1.Efficacy of cyclosporin with corticotrophin for refractory ulcerative colitis[J]. Hepatogastroentero1ogy,2003 Jan-Feb;50(49):91-94.
[53]Ouyang Q,Tandon R,Goh KL,et al.Management consensus of inflammatory bowel disease for the Asia-Pacific region[J].J Gastroenterol Hepatol,2006 Dec;21(12): 1772-1782..
[54]Cameron EA,Binnie JA,Balan K,et al.Oral prednisolone metasulphobenzoate in the treatment of active ulcerative colitis.Scand J Gastroenterol,2003 May;38(5):535-537.
[55]Durai D,Hawthorne AB.Review article:how and when to use ciclosporin in ulcerative colitis[J]. Aliment Pharmacol Ther,2005 Nov 15;22(10):907-916.
[56]Danese S,De la Rue SA,Gasbarrini A.Antibody to alpha4beta7 integrin for ulcerative colitis.N Engl J Med,2005 Sep15;353(11):1180-1181.
[57]王群英,陈村龙,孙勇,等.溃疡性结肠炎患者菌群分析结果的研究[J].中国微生态学杂志,2002,14(1): 31-32.
[58]辛光宾,李立新.地尔硫与环丙沙星联用治疗溃疡性结肠炎 16 例分析[J].辽宁医学杂志,2000,14(4):213.
[59]Ohkusa T,Nomura T,Terai T,et al.Effectiveness of antibiotic combination therapy in patients with active ulcerative colitis:A randomized,controlled pilot trial with long-term follow-up[J]. Scand J Gastroenterol,2005 Nov;40(11):1334-1342.
[60]Gionchetti P,Rizzello F,Morselli C,et al.Management of inflammatory bowel disease:does rifaximin offer any promise?Chemotherapy,2005;51 Suppl 1:96-102.
[61]Kozuch PL,Hanauer SB.Treatment of inflammatory bowel disease:a review of medical therapy.World J Gastroenterol,2008 Jan 21;14(3):354-377.
[62]Satror RB.Mechanisms of disease:pathogenesis of crohn’s disease and ulcerative colitis.Gastroenterol Hepatol,2006,3(7):390-406.
[63]Kato K,Mizuno S,Umesaki Y,et al.Randomized placebo-controlled trial assessing the effect of bifidobacteria-fermented milk on active ulcerative colitis.Aliment Pharmacol Ther,2004,20(10):1133-1141.
[64]Ishikawa H,Akedo I,Umesaki Y,et al.Randomized controlled trial of the effect of bifidobacteria-fermented milk on ulcerative colitis.J Am Coll Nutr,2003 Feb;22(1):56-63.
[65]Chapman TM,Plosker GL,Fiqqitt DP.Spotlight on VSL#3 probiotic mixture in chronic inflammatory bowel diseases.BioDrugs,2007;21(1):61-63.
[66]Bibiloni R,Fedorak RN,Tannack GW,et al.VSL#3 probiotic-mixture induces remis -sion in patients with active ulcerative colitis.Am J Gastroenterol, 2005 Jul;100(7): 1539- 1546.
[67]Chermesh I,Eliakim R.Probiotics and the gastrointestinal tract:Where are we in 2005?World J Gastroenterol,2006 Feb 14;12(6):853-857.
[68]Kruis W, Fric P, Pokrotnieks J, et al. Maintaining remission of ulcerative colitis with probiotic Escherichia coliNissle 1917 is as effective as with standard mesalazine[J].Gut,2004 Nov; 53(11):1617-1623.
[69]Famularo G, Mosca L, Minisola G, et al. Probiotic lactobacilli a new perspective for the treatment of inflammatory bowel disease[J].Curr Pharm Des, 2003;9(24): 1973-1980.
[70]Tursi A,Brandimarte G,Giorgetti GM,et al.Low-dose balsalazide plus a high-potencyprobiotic preparation is more effective than balsalazide alone or mesalazine in the treatment of acute mild-to-moderate ulcerative colitis.Med Sci Monit,2004,10(11):PI 126-131.
[71]Zocco MA,dal Verme LZ,Cremonini F,et al.Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitis.Aliment Pharmacol Ther,2006 Jun 1;23(11):1567-1574.
[72]Mimura T,Rizzello F,Helwig U,et al.Once daily high dose probiotic therapy (VSL#3) for maintaining remission in recurrent or refractory pouchitis.Gut,2004 Jan;53(1)108-114.
[73]Fedorak RN,Madsen KL.Probiotics and the management of inflammatory bowel disease.Inflamm Bowel Dis.2004 May;10(3):286-299.
[74]Tursi A,Brandimarte G,Giorqett GM,et al.Balsalazide and/or high-potency probiotic mixture(VSL#3)in maintaining remission after attack of acute,uncomplicated diverticulitis of the colon.Int J Colorectal Dis,2007 Sep;22(9):1103-1108.
[75]Rioux KP,Fedorak RN.Probiotics in the treatment of inflammatory bowel disease.J Clin Gastroenterol,2006,40(3):260-263.
[76]Shanahan F.Probiotics in inflammatory bowel disease-therapeutic rationale and role.Adv Dru Deliv Rev,2004 Apr 19;56(6):809-818.
[77]Ben-Arye E,Goldin E,Wengrower D,et al.Wheat grass juice in the treatment of active distal ulcerative colitis:a randomized double-blind placebo-controlled trial.Scand J Gastroenterol,2002 Apr;37(4):444-449.
[78]Langmead L,Dawson C,Hawkins C,et al.Antioxidant effects of herbal therapies used by patients with inflammatory bowel disease:an in vitro study.Aliment Pharmacol Ther,2002 Feb;16(2):197-205.
[79]吕永慧.炎症性肠病的中医治疗[J].中国实用内科杂志,2003, 19 (5): 457-459.
[80]张振书,周殿元.溃疡性结肠炎的内科治疗[J].胃肠病学,2004,9(4):251-254.
[81]宋良,张进峰,郜艳丽.中西医结合治疗慢性非特异性结肠炎 131 例[J].河南中医学院学报,2003,18(1):47-48.
[82]夏金荣,张少虹,杨杰.中西药联合灌肠治疗溃疡性结肠炎的疗效观察.临床消化病杂志,2002,14(1):19-21.
[83]苏娟萍,冯五金.肠必安灌肠治疗溃疡性结肠炎的临床研究[J].山西中医学院学报,2006,7(3):30-31.
[84] 朱 凤 玲 . 中 药 灌 肠 治 疗 慢 性 溃 疡 性 结 肠 炎 50 例 [J]. 实 用 中 医 内 科 杂志,2005,19(1):70-71.
[85]杜群,李红,王建华等.溃结灵对溃疡性结肠炎大鼠结肠粘膜 NF-κB p65 蛋白表达及血清 TNF-α含量的影响.广州中医药大学学报,2007,5(24):396-399.
[86]陈英群,马贵同,冯怡等.清肠泡腾栓对溃疡性结肠炎模型大鼠细胞因子的影响.中医杂志,2007,7(48):638-640.
[87]段永强,程畅和,成映霞等.痛泻二草方对溃疡性结肠炎模型大鼠血清IL-2含量及肠黏膜NO含量、NOS活性的影响.中国中医药信息杂志,2007,1(14):34-36.
[88]Papa A,Danese S,Gasbarrini G,et al.When can unfractionated heparin really be useful in the treatment of ulcerative colitis?Gastroenterology,2001 Apr;120(5):1306-1307.
[89]He G,Ouyang Q,Chen D,et al.The microvascular thrombi of colonic tissue in ulcerative colitis.Dig Dis Sci,2007 Sep;52(9):2236-2240.
[90]贺国斌.溃疡性结肠炎的血栓前状态与肝素治疗[J].国外医学#内科学分册,2000,27(6):238-241.
[91]贺国斌,欧阳钦.肝素治疗右旋葡聚糖硫酸钠诱导小鼠结肠炎的疗效观察[J].中华消化杂志,2002,22(9):546-549.
[92]Hostutler RA,Luria BJ,Johnson SE,et al.Antibiotic-responsive histiocytic ulcerative colitis in 9 dogs.J Vet Intern Med,2004,18(4):499-504.
[93]Zezos P,Papaioannou G,Nikolaids N,et al.Low-molecular-weight heparin(enoxaparin) as adjuvant therapy in the treatment of active ulcerative colitis:a randomized,controlled,comparative study.Aliment Pharmacol Ther,2006 May;23(10):1443-1453.
[94]Shen J,Ran ZH,Tong JL,et al.Meta-analysis:The utility and safety of heparin in the treatment of active ulcerative colitis.Aliment Pharmacol Ther,2007 Sep;26(5):653-663.
[95]Dotan I,Hallak A,Arber N,et al.Low-dose low-molecular weight heparin(enoxaparin)is effective as adjuvant treatment in active ulcerative colitis:an open trial.Digestive Disease and Sciences,2001 Oct;46(10):2239-2244.
[96]徐德亮,穆平,沙士义等.溃疡性结肠炎血液流变学及抗凝治疗的临床研究.胃肠病学和肝病学杂志,2005,4(14):413
[97] 江学良 , 刘涛 . 肝素治疗顽固性溃疡性结肠炎一例 [J]. 世界华人消化杂志,1999,7(8):694.
[98]McGilligan VE,Wallace JM,Heavey PM,et al.Hypothesis about mechanisms through which nicotine might exert its effect on the interdependence of inflammation and gut barrier function in ulcerative colitis.Inflamm Bowel Dis,2007 Jan;13(1):108-115.
[99]Sandborn WJ,Tremaine WJ,Offord KP,et al.Transdermal nicotine for mildly to moderately active ulcerative colitis:a randomized,double blind,placebo-controlled trial.Ann Intern Med,1997 Mar 1;126(5):364-371.
[100]Ingram JR,Rhodes J,Evans BK,et al.Preliminary observations of oral nicotine therapy for inflammatory bowel disease:an open-label phase Ⅰ - Ⅱ study of tolerance.Inflamm Bowel Dis,2005 Dec;11(12):1092-1096.
[101]Hanauer SB.Review article:the long-term management of ulcerative colitis.Aliment Pharmacol Ther,2004 Oct;20(Suppl 4):97-101
[102]Green JT,Richardson C,Marshall RW,et al.Nitric oxide mediates a therapeutic effect of nicotine in ulcerative colitis[J].Aliment Pharmacol Ther,2000 Nov;14(11):1429- 1434.
[103]Bartnik W.Inflammatory bowel disease Polish contribution [J].J Physiol Pharmacol,2003,54(Suppl 3):205-210.
[104]Fuss IJ.Cytokine network in inflammatory bowel disease.Curr Drug Targets Inflamm Allergy.2003 Jun;2(2):101-112.
[105]Braegger CP,Macdonald TT.Immune mechanisms in chronic inflammatory bowel disease.Ann Allergy,1994 Feb;72(2):135-141.
[106]Bhan AK,Mizoguchi E,Smith RN,et al.Colitis in transgenic and knockout animals as models of human inflammatory bowel disease.Immunol Rev,1999 Jun;169:195–207.
[107]Hanauer SB.Inflammatory bowel disease:epidemiology,pathogenesis,and therapeutic opportunities.Inflamm Bowel Dis,2006 Jan;12 Suppl 1:S3-9.
[108]丁伟群,林庚金,徐三荣等.溃疡性结肠炎发病中白介素水平的变化[J].复旦学报(医学科学版),2001,28(4):330-333.
[109]Kelly-Welch AE, Hanson EM, Boothby MR,et al.Interleukin-4 and interleukin-13 signaling connections maps.Science,2003 Jun 6;300(5625):1527-1528.
[110]Carol M,Lambrechts A,Van Gossum A,et al.Spontaneous secretion of interferon gamma and interleukin 4 by human intraepithelial and lamina propria gut lymphocytes[J].Gut,1998 May;42(5):643-649.
[111]Elson CO,Beagley KW,Sharmanov AT,et al.Hapten-induced model of murine inflammatory bowel disease.Mucosal immune responses and protection by tolerance.J Immunol,1996 Sep 1;157(5):2174–2185.
[112]Nielsen OH,Koppen T,Rudiger N,et al.Involvement of interleukin-4 and-10 in inflammatory bowel disease.Dig Dis Sci,1996 Sep;41(9):1786-1793.
[113]Hogaboam CM,Vallance BA,Kumar A,et al.Therapeutic effects of interleukin-4 gene transfer in experimental inflammatory bowel disease.J Clin Invest,1997 Dec 1;100(11):2766-2776.
[114]Macdonald TT. Viral vectors expressing immunoregulatory cytokines to treat inflammatory bowel disease[J].Gut,1998,42(4):460-461.
[115]West GA,Matsuura T,Levine AD,et al.Interleukin-4 in inflammatory bowel disease and mucosal immune reactivity[J].Gastroenterology,1996,110(6):1683-1695.
[116]Mittal RD,Bid HK,Ghoshal UC.IL-1 receptor antagonist (IL-1Ra) gene polymorphism in patients with inflammatory bowel disease in India. Scand J Gastroenterol. 2005 Jul;40(7):827-831.
[117]Rogy MA,Beinhauer BG,Reinisch W,et al.Transfer of interleukin-4 and Interleukin-10 in patients with severe inflammatory bowel disease of the rectum.Hum Gene Ther,2000 Aug 10;11(12):1731-1741.
[118]Blumberg RS,Saubermann LJ,Strober W.Animal models of mucosal inflammation and their relation to human inflammatory bowel disease.Crurr Opin Immunol,1999Dec;11(6):648-656.
[119]Sawa Y, Oshitani N, Adachi K,et al. Comprehensive analysis of intestinal cytokine messenger RNA profile by real-time quantitative polymerase chain reaction in patients with inflammatory bowel disease.Int J Mol Med,2003;11(2):175-179.
[120]Inoue S, Matsumoto T, Iida M, et al. Characterization of cytokine expression in the rectal mucosa of ulcerative colitis: correlationwith disease activity. Am J Gastroenterol, 1999 Sep;94(9):2441-2446.
[121]Erdman S E,Rao V P,Poutahidis T,et al.CD4( +)CD25(+) regulatory lymphocytes require interleukin-10 to interrupt colon carcinogenesis in mice[J].Cancer Res,2003 Sep 15;63(18):6042-6050.
[122]Rennick DM,Fort MM . Lessons from genetically engineered animal models.XII.IL-10-deficient (IL-10-/-) mice and intestinal inflammation[J].Am J Physiol Gastrointest Liver Physiol,2000,278(6):G 829-833.
[123]Latinne D,Fiasse R.New insights into the cellular immunology of the intestine in relation to the pathophysiology of inflammatory bowel diseases.Acta Gastroenterol Belg,2006 Oct-Dec;69(4):393-405.
[124]Joel V,Weinstock,Arthur Blum,et al.Substance P Regulates Th1-Type Colitis in IL-10 Knockout Mice[J].J Immunol,2003;171(2):3762-3767.
[125]Gasche C,Bakos S,Dejaco C,et al.IL-10 secretion and sensitivity in normal human intestine and inflammatory bowel disease.J Clin Immunol,2000 Sep;20(5):362-370.
[126]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 Jul;153(1):121-130.
[127] Mitsuyama K,Tomiyasu N,Takaki K,et al.Interleukin-10 in the pathophysiology of inflammatory bowel disease:increased serum concentrations during the recovery phase.Mediators Inflamm,2006;2006(6):26875.
[128]Melgar S,Yeung MM,Bas A,et al.Over-expression of interleukin 10 in mucosal T cells of patients with active ulcerative colitis. Clin Exp Immunol,2003 Oct;134(1): 127-137.
[129]Driessler F,Venstrom K,Sabat R,et al.Molecular mechanisms of interleukin-10-mediated inhibition of NF-kappa B activity:a role for p50.Clin Exp Immunol,2004 Jan;135(1):64-73.
[130]Lindsay JO,CiesielskiC J,ScheininT,et al.Local delivery of adenoviral vectors encoding murine interleukin-10 induces colonic interleukin-10 production and is therapeutic for murine colitis[J].Gut,2003 Jul;52(7):981-987.
[131]Lindsay JO,Sandison A,Cohen P,et al.IL-10 gene therapy is therapeutic for dextran sodium sulfate induced murine colitis[J].DigDis Sci,2004 Aug;49(7-8):1327-1334.
[132]Schreiber S,Fedorak RN,Nielsen OH,et al.Safety and efficacy of recombinant human interleukin 10 in chronic active Crohn’s disease. Crohn’s Disease IL-10 Cooperative Study Group[J].Gastroenterology,2000;119(6):1461-1472.
[133]Bickston SJ,Cominelli F.Recombinant interleukin 10 for the treatment of active Crohn’s disease:lessons in biologic therapy[J].Gastroenterology,2000 Dec;119(6): 1781- 1783.
[134]Fedorak RN,Gangl A,Elson CO,et al.Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn’s disease.The Interleukin 10 Inflammatory Bowel Disease Cooperative Study Group [J].Gastroenterology,2000;119(6):1473-1482.
[135]Schreiber S,Hernig T,Thiele HG,et al.Immmunoregulatory role of interleukin-10 in patients with inflammatory bowel disease[J].Gastroenterology,1995 May;108(5):1434-1444.
[136]Niedergang F,Didierlaurent A,Kraehenbuhl JP,et al.Dendritic cells:the host Achille’s heel for mucosal pathogens?Trends Microbiol,2004 Feb;12(2):79-88.
[137]Sandborn WJ,Targan SR[J].Biologic therapy of inflammatory bowel disease.Gastroenterology,2002 May;122(6):1592-1608.
[138] 吕 农 华 , 罗 玲 玉 . 白 细 胞 介 素 与 炎 症 性 肠 病 [J]. 中 国 实 用 内 科 杂志.2007,18(27):1437-1439.
[139]Nikolaus S,Rutgeerts P,Fedorak R,et al.Interferon beta-1a in ulcerative colitis: a placebo controlled,randomised,dose escalating study[J].Gut,2003 Sep;52(9):1286-1290.
[140]Fuss IJ,Neurath M,Boirivant M,et al.Disparate CD+4 lamina propria(LP)lymphokine secretion profiles in inflammatory bowel disease.Crohn’s disease LP cells manifest increased Secretion of IFN-gamma,whereas ulcerative colitis LP cells manifest increased secretion of IL-5[J].J Immunol,1996 Aug;157(3):1261-1270.
[141]Schlottmann K,Wachs F P,Grossmann J,et al.Interferon gamma downregulates IL-8 production in primary human colonic epithelial cells without induction of apoptosis[J].Int J Colorectal Dis,2004 Sep;19(5):421-429.
[142]Sventoraitte J,Zvirbliene A,Kiudelis G,et al.Immune system alterations in patients with inflammatory bowel disease during remission.Medicina(Kaunas), 2008;44(1):27-33.
[143]Simpson SJ,Hollander GA,Mizoguchi E,et al.Expression of pro-inflammatory cytokines by TCR alpha beta+ and TCR gamma delta+T cells in an experimental model of colitis.Eur J Immunol,1997 Jan;27(1):17-25.
[144]Ito R,Shin-Ya M,Kishida T,et al.Interferon-gamma is causatively involved in experimental inflammatory bowel disease in mice.Clin Exp Immunol,2006 Nov;146(2):330-338.
[145]Mizoguchi A,Mizoguchi E,Chiba C,et al.Cytokine imbalance and autoantibody production in T cell receptor-alpha mutant mice with inflammatory bowel disease.J Exp Med,1996;183(3):847-856.
[146]Takahashi I,Iijima H,Katashima R,et al.Clonal expansion of CD4+TCRbetabeta+T cells in TCR alpha-chain-deficient mice by gut-derived antigens.J Immunol,1999;162(3):1843-1850.
[147]Waidmann M,Allemand Y, Lehmann J,et al.Microflora reactive IL-10 producing regulatory T cells are present in the colon of IL-2 deficient mice but lack efficacious inhibition of IFN-gamma and TNF-alpha production[J].Gut,2002 Feb; 50(2): 170-179.
[148]Malek TR.The main function of IL-2 is to promote the development of T regulatorycells[J].J Leukoc Biol,2003 Dec;74(6):961-965.
[149]Kullberg MC,Ward JM,Gorelick PL,et al.Helicobacter hepaticus triggers colitis in specific-pathogen-free interleukin-10 ( IL-10)-deficientmice through an IL-12-and gamma interferon-depend-entmechanism[J].Infect Immun,1998 Nov;66(11): 5157- 5166.
[150]Elson CO,Cong Y,McCracken VJ,et al.Experimental models of inflammatory bowel disease reveal innate, adaptive, and regulatory mechanisms of host dialogue with the microbiota[J].Immun Rev,2005 Aug;206:260-276.
[151]Ohman L, Franzen L,Rudolph U,et al.Regression of Peyers'patches in Gai2 deficient mice prior to colitis is associated with reduced expression of Bcl-2 and increased apoptosis[J].Gut,2002 Sep;51(3):392-397.
[152]Dieleman LA,Goerres MS,Arends A,et al.Lactobacihhus GG prevents recurrence of colitis inHLA-B27 transgenic rats after antibiotic treatment[J].Gut,2003 Mar;52(3): 370-376.
[153]Wirtz S,Finotto S,Kanzler S,et al.Cutting edge: chronic intestinal inflammation in STAT-4 transgenic mice:characterization of disease and adoptive transfer by TNF-plus IFN-gamma-producing CD4+T cells that respond to bacterial antigens[J].J Immunol,1999 Feb;162(4):1884-1888.
[154]Madara JL,Podolsky DK,King NW,et al.Characterization of spontaneous colitis in cotton-top tamarins(Saguinus oedipus)and its response to sulfasalazine[J].Gastroenterology, 1985 Jan;88(1 Pt 1):13-19.
[155]Sundberg JP,Elson CO,Bedigian H,et al.Spontaneous,heritable colitis in a new substrain of C3H/HeJ mice.Gastroenterology,1994 Dec,107(6):1726-1735.
[156]Matsumoto S,Okabe Y,Setoyama H,et al.Inflammatory bowel disease-like enteritis and caecitis in a senescence accelerated mouse P1/Yit strain.Gut,1998;43(1):71-78.
[157]Aranda R,Sydora BC,McAllister PL,et al.Analysis of intestinal lymphocytes in mouse colitis mediated by transfer of CD4+,CD45RBhigh T cells to SCID recipients.J Immunol,1997;158(7):3464-3473.
[158]Wirtz S,Neufert C,Weigmann B,et al. Chemically induced mouse models ofintestinal inflammation.Nat Protoc,2007;2(3):541-546.
[159]Neurath MF,Fuss I,Kelsall BL,et al.Antibodies to interleukin 12 abrogate established experimental colitis in mice[J].J Exp Med,1995 Nov 1;182(5):1281-1290.
[160]Bailón E, Camuesco D,Nieto A,et al.The intestinal anti-inflammatory effects of the novel agent UR-1505 in the TNBS model of rat colitis are mediated by T-lymphocyte inhibition.Biochem Pharmacol,2007 Nov 15;74(10)1496-1506.
[161]Okayasu I,Hatakeyama S,Yamada M,et al.A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice[J].Gastroenterology,1990 Mar;98(3):694-702.
[162]Sivakumar PV,Westrich GM, Kanaly S,et al.Interleukin 18 is a primary mediator of the inflammation associated with dextran sulphate sodium induced colitis: blocking interleukin 18 attenuates intestinal damage[J].Gut,2002 Jun;50(6):812-820.
[163]Cooper HS,Murthy S,Kido K,et al.Dysplasia and cancer in the dextran sulfate sodium mouse colitis model.Relevance to colitis-associated neoplasia in the human:a study of histopathology,B-catenin and p53 expression and the role of inflammation.Carcinogenesis,2000,21(4):757-768.
[164]Guo SM,Tong HB,Bai LS,et al.Effect of traditional Chinese medicinal enemas on ulcerative colitis of rats[ J].World J Gastroenterol,2004 Jul 1;10(13):1914-1917.
[165]Glick ME,Falchuk ZM.Dinitrochlorobenzene-induced colitis in the guinea-pig:studies of colonic lamina propria lymphocytes[J].Gut,1981 Feb;22(2): 120-125.
[166]Boirivant M,Fuss IJ,Chu A,et al.Oxazolone colitis:a murine model of T helper cell type 2 colitis treatable with antibodies to interleukin 4[J].J Exp Med.1998 Nov;188(10):1929–1939.
[167]Kojima R,Kuroda S,Ohkishi T, et al.Oxazolone-induced colitis in BALB/C Mice: a new method to evaluate the efficacy of therapeutic agents for ulcerative colitis[J].J Pharmacol Sci,2004 Nov;96(3):307-313.
[168]Heller F,Fuss IJ,Nieuwenhuis EE,et al.Oxazolone colitis,a Th2 colitis model resembling ulcerative colitis,is mediated by IL-13-producing NK-T cells[J].Immunity,2002 Nov,17(5): 629-638.
[169]Thomson JA,Troutt AB,Kelso A.Contact sensitization to oxazolone:involvement of both interferon-gamma and interleukin-4 in oxazolone-specific Ig and T-cell respo- nses.Immunology,1993 Feb;78(2):185-192.
[170]Sun X,Somada S,Shibata K,el al.A critical role of CD30 ligand/CD30 in controlling inflammatory bowel diseases in mice[J].Gastroenterology,2008 Feb;134(2):447-458.
[171]Arseneau KO,Pizarro TT,Cominelli F.Discovering the cause of inflammatory bowel disease:lessons from animal models.Curr Opin Gastroenterol,2000 Jul;16(4):310-317.
[172]Philippe D,Dubuquoy L,Groux H,et al.Anti-inflammatory properties of the mu opioid receptor support its use in the treatment of colon inflammation[J].J Clin Invest,2003 May;111(9):1329-1338.
[173]Luk HH,Ko JK,Fung HS,et al.Delineation of the protective action of zinc sulfate on ulcerative colitis in rats.Eur J Pharmacol,2002 May 17;443(1-3):197-204.
[174]韩英,村田有志,伊东重豪等.长期应用尼古丁对噁唑酮诱导的实验性小鼠肠炎模型的影响及其机制探讨.中华消化杂志,2001;21(8):473-476.
[175]Fabia R,Ar’Rajab A,Johansson ML,et al.The effect of exogenous administration of Lactobacillus reuteri R2LC and oat fiber on acetic acid-induced colitis in the rat.Scand J Gastroenterol,1993 Feb;28(2):155-162.
[176]Strober W,Fuss IJ,Blumberg RS.The immunology of mucosal models of inflammation.Annu Rev Immunol,2002;20:495–549.
[177]Neurath MF,Finotto S,Glimcher LH.The role of Th1/Th2 polarization in mucosal immunity.Nat Med,2002 Jun;8(6):567-573.
[178] Bamias G,Sugawara K,Pagnini C,et al.The Th1 immune pathway as a therapeutic target in Crohn's disease.Curr Opin Investig Drugs,2003 Nov;4(11):1279-1286.
[179] Okazawa A,Kanai T,Watanabe M,et al.Th1-mediated intestinal inflammation in Crohn's disease may be induced by activation of lamina propria lymphocytes through synergistic stimulation of interleukin-12 and interleukin-18 without T cell receptor engagement.Am J Gastroenterol,2002 Dec;97(12):3108-3117.
[180]Mizoguchi A,Mizoguchi E,Saubermann LJ,et al.Limited CD4 T-cell diversityassociated with colitis in T-cell receptor alpha mutant mice requires a T helper 2 environment.Gastroenterology,2000 Oct;119(4):983-995.
[181]Van Damme N,De Keyser F,Demetter P,et al.The proportion of Th1 cells,which prevail in gut mucosa,is decreased in inflammatory bowel syndrome.Clin Exp Immunol,2001 Sep;125(3):383-390.
[182]Salem ML.Estrogen,a double-edged sword:modulation of TH1-and TH2-mediated inflammations by differential regulation of TH1/TH2 cytokine production.Curr Drug Targets Inflamm Allergy,2004 Mar;3(1):97-104.
[183]Boirivant M,Strober W,Fuss IJ.Regulatory cells induced by feeding TNP-haptenated colonic protein cross-protect mice from colitis induced by an unrelated hapten.Inflamm Bowel Dis,2005 Jan;11(1):48-55.
[184]Neurath M,Fuss I,Strober W.TNBS-colitis.Int Rev Immunol,2000;19(1):51-62.
[185]Cottrez F,Hurst SD,Coffman RL,et al.T regulatory cells 1 inhibit a Th2-specific response in vivo.J Immunol,2000 Nov 1;165(9):4848-4853.
[186]中华医学会消化病学分会.对炎症性肠病诊断治疗规范的建议[J].中华消化杂志,2001;21(4):236-239.
[187]Truelove SC,Richards WC.Biopsy studies in ulcerative colitis[J]. Br Med J,1956 Jun 9;1(4979):1315-1318.
[188]中国炎症性肠病协作组.3100 例溃疡性结肠炎住院病例回顾分析.中华消化杂志,2006,26(6):368-372.
[189]Jani N, Regueiro MD.Medical therapy of ulcerative colitis[J].Gastroenterol Clin North Am,2002 Mar;31(1):147-166.
[190]陈劲勇,周志光,王跃平.柳氮磺吡啶加中药与单用柳氮磺吡啶在溃疡性结肠炎中的疗效比较[J].中国新药与临床杂志,2003,22(5):287-288.
[191]Hanauer SB.Update on the etiology, pathogenesis and diagnosis of ulcerative colitis.Nat Clin Pract Gastroenterol Hepatol,2004 Nov;1(1):26-31.Review.
[192]庞艳华,郑长清,王轶淳等.IL-4 和 IL-13 在溃疡性结肠炎中的表达.胃肠病学和肝病学杂志,2005,4(14):410-412.
[193]Kimura I,Kawasaki M,Nagahama S,et al.Determination of the active moiety ofBX661A,a new therapentic agent for ulcerative colitis,by studying its therapeutic effects on ulcerative colitis induced by dextran sulfate sodium in rats[J].Arznei mittelforschung,1998 Nov;48(11):1091-1096.
[194] 木 村 伊 佐 美 , 永 滨 忍 , 川 崎 真 规 . 巴 柳 氮 的 药 理 学 研 究 [J]. 日 药 理志,1997,109(2):85-94.
[195]McNeil HP, Simpson RJ,Chesterman CN, et al.Antiphospholipid antibodies are directed against a complex antigen that includes a lipid binding inhibitor of coagulation β2-glycoproteinⅠ (apolipoprotein H)[J].Proc Natl Acad Sci USA,1990;87(11): 4120-4124.
[196]Galli M, Comfuius P,Maassen C, et al.Anticardiolipin antibodies(ACA) directed not to cardiolipin but to a plasma cofactor[ J].Lancet,1990;335(8705):1544-1547.
[197]Davies ML,Young SP,Welsh K,et al.Immune responses to native beta(2)-glycoprotein I in patients with systemic lupus erythematosus and the antiphospholipid syndrome.Rheumatology(Oxford),2002 Apr;41(4):395-400.
[198]Kalt M,Gertner E.Antibodies to beta 2-glycoprotein I and cardiolipin with symptoms suggestive of systemic lupus erythematosus in parvovirus B19 infection.J Rheumatol,2001 Oct;28(10):2335-2336.
[199]Gerorge J,Blank M,Lery Y,et al.Differential effects of anti-beta2-glycoprotein I antibodies on endothelial cells and on the manifestations of experimental antiphospholipid syndrome.Circulation,1998 Mar;97(9):900-906.
[200]Arvieux J,Roussel B, Jacob MC, et al.Measurement of anti-phospholipid antibodies by ELISA using beta 2-glycoproteinⅠ as an antigen[J].J Immunol Methods,1991 Oct 25;143(2):223-229.
[201]Bondanza A,Sabbadini MG,Pellegatta F,et al.Anti-beta2-glycoprotein I antibodies prevent the De-activation of platelets and sustain their phagocytic clearance.J Autoimmun,2000 Dec;15(4):469-477.
[202]Meroni PL, Raschi E, Testoni C, et al.Statins prevent endothelial cell activation induced by antiphospholipid (anti-beta2-glycoproteinⅠ ) antibodies:effect on the proadhesive and proinflammatory phenotype[J].Arthritis Rheum,2001 Dec,44(12):2870-2878.
[203]Delpapa N, Sheng YH, Raschi E, et al.Human beta 2-glycoproteinⅠ binds to endothelial cells through a cluster of lysine resiclues that are critical for anionic phospholipid binding and offers epitopes for anti-beta 2-glycoproteinⅠantibodies[ J].J Immunol,1998 Jun;160(11):5572-5578.
[204]Campieri M,Adamo S,Valpiani D,et al.Oral beclometasone dipropionate in the treatment of extensive and left-sided active ulcerative colitis:a multicentre randomised study.Aliment Pharmacol Ther,2003 Jun 15;17(12):1471-1480.
[205]Graef V, Baggenstoss AH, Sauer WG, et al.Venous thrombosis occurring in nonspe -cific ulcerative colitis: a necropsy study[ J].Arch Intern Med,1966;117(2):377-382.
[206]Webberley MJ, Hart MT, Melikian V. Thromboembolism in inflammatory bowel Disease: role of platelets.Gut,1993 Feb;34(2):247-251.
[207]Lam A,Borda IT,Inwood MJ,et al. Coagulation studies in ulcerative colitis and Crohn's disease.Gastroenterology,1975 Feb;68(2):245-251.
[208]Papa A, Danese S, Gasbarrini A, Gasbarrini G. Review article: potential therapeutic applications and mechanisms of action of heparin in inflammatory bowel disease. Aliment Pharmacol Ther,2000 Nov;14(11):1403-1409.
[209]张连峰,田曙光,王国新.溃疡性结肠炎患者血小板功能状态的研究[J].中国实用内科杂志, 2000, 20(2): 98-99.
[210]吴曦,刘新光,田宇,等.炎症性肠病患者的临床表现(附 201 例临床分析) [ J].中国实用内科杂志, 2006, 26 (3): 190 -193.
[211]Dong WG, Liu SP, Zhu HH, et a.l Abnormal function of platelets and role of angelica sinensis in patients with ulcerative colitis[J].World J Gastroenterol,2004 Feb 15;10(4): 606-609.
[212]Singh AK.Immunopathogenesis of the antiphospholipid antibody syndrome: an update[J].Curr Opin Nephrol Hypertens,2001 May;10(3):355-358.