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dextran sulfate sodium-induced colitis-associated neoplasia:a promising model for the development of chemopreventive interventions

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Acta Pharmacologica Sinica 2007年第9期28卷 1450-1459页

作者： Margie Lee CLAPPER Harry Stanley COOPER Wen-Chi Lee CHANG Divisions of Population Science Medical Science Fox Chase Cancer CenterPhiladelphiaPA 19111USA

Individuals diagnosed with ulcerative colitis face a significantly increased risk ofdeveloping colorectal dysplasia and cancer during their *** date,littleattention has been given to the development of a chemopreventive interventionfor this high-risk *** mouse model of dextran sulfate sodium (DSS)-induced colitis represents an excellent preclinical system in which to both charac-terize the molecular events required for tumor formation in the presence of inflam-mation and assess the ability of select agents to inhibit this *** admin-istration of DSS in drinking water results in the establishment of chronic colitisand the development of colorectal dysplasias and cancers with pathological fea-tures that resemble those of human colitis-associated *** incidenceand multiplicity of lesions observed varies depending on the mouse strain used(ie,Swiss Webster,C57BL/6J,CBA,ICR) and the dose (0.7%-5.0%) and schedule(1-15 cycles with or without a subsequent recovery period) of *** incidenceof neoplasia can be increased and its progression to invasive cancer acceleratedsignificantly by administering DSS in combination with a known colon carcinogen(azoxymethane (AOM),2-amino-3-methylimidazo[4,5-f]quinoline (IQ),2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)) or *** recent induction ofcolitis-associated neoplasia in genetically defined mouse strains has providednew insight into the role of specific genes (ie,adenomatous polyposis coli (Apc),p53,inducible nitric oxide synthase (iNOS),Msh2) in the development of colitis-associated *** data from chemopreventive intervention studiesdocument the efficacy of several agents in inhibiting DSS-induced neoplasiaand provide great promise that colitis-associated colorectal neoplasia is a pre-ventable disease.

关键词： colorectal colitis chemoprevention dextran sulfate sodium mouse models

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Involvement of lymphocytes in dextran sulfate sodium-induced experimental colitis

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World Journal of Gastroenterology 2006年第2期12卷 302-305页

作者： Tae Woon Kim Jae Nam Seo Young Ho Suh Hyo Jin Park Ju Hyun Kim Ji Young Kim Kwon Ik Oh Department of Pathology Hallym University College of MedicineChuncheonKorea Division of Metabolic Diseases Department of Biomedical SciencesNational Institute of HealthSeoulKorea Graduate Program of Immunology and Department of Pathology Seoul National University College of MedicineSeoulKorea

AIM： To investigate the roles of lymphocytes in the development of dextran sulfate sodium-induced colitis. METHODS： Using various doses of dextran sulfate sodium （DSS）, we induced colitis in wild-type B6 control and Rag-1 knockout （H-2b haplotype） mice, and evaluated the colitis in terms of symptomatic and histologic parameters, such as weight loss, survival, severity of diarrhea, shortage of colon length and histological changes. Symptomatic parameters were checked daily and histological changes were scored. RESULTS： Although development of colitis in Rag-1 knockout mice treated with high dose （5%） of DSS was comparable to that in B6 control mice, colitis progression was much more tolerable in Rag-1 knockout mice compared to than in B6 mice treated with low dose （1.5%） DSS. Symptomatic parameters as well as histopathologic changes were improved in Rag-1 knockout mice. CONCLUSION： These results indicate that the presence of lymphoo/tes contributes to colitis progression at low dose of DSS stimulation. Lymphoo/tes may play roles as an aggravating factor in DSS-induced colitis.

关键词： dextran sulfate sodium Colitis Lymphocyte Rag-1 Knockout

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Antibody to eosinophil cationic protein suppresses dextran sulfate sodium-induced colitis in rats

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World Journal of Gastroenterology 2005年第29期11卷 4505-4510页

作者： Kazuko Shichijo Kazuya Makiyama Chun-Yang Wen Mutsumi Matsuu Toshiyuki Nakayama Masahiro Nakashima Makoto Ihara Ichiro Sekine Department of Molecular Pathology Atomic Bomb Disease Institute Nagasaki University Graduate School of Biomedical Sciences 1-12-4 Sakamoto Nagasaki 852-8523 Japan Department of Endoscopy Nagasaki University School of Medicine Hospital and Clinics 1-12-4 Sakamoto Nagasaki 852-8523 Japan Department of Digestive Disease the Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing 210008 Jiangsu Province China Tissue and Histopathology Section Atomic Bomb Disease Institute Nagasaki University Graduate School of Biomedical Sciences 1-12-4 Sakamoto Nagasaki 852-8523 Japan Radiation Biophysics Atomic Bomb Disease Institute Nagasaki University Graduate School of Biomedical Sciences 1-12-4 Sakamoto Nagasaki 852-8523 Japan

AIM： To produce an antibody against rat eosinophil cationic protein （ECP） and to examine the effects of the antibody in rats with dextran sulfate sodium （DSS）-induced colitis. METHODS： An antibody was raised against rat ECP. Rats were treated with 3% DSS in drinking water for 7 d and received the antibody or normal serum. The colons were examined histologically and correlated with clinical symptoms. Immunohistochemistry and Western blot analysis were estimated as a grade of inflammation. RESULTS： The ECP antibody stained the activated eosinophils around the injured crypts in the colonic mucosa. Antibody treatment reduced the severity of colonic ulceration and acute clinical symptoms （diarrhea and/or bloodstained stool）. Body weight gain was significantly greater and the colon length was significantly longer in anti-ECPtreated rats than in normal serum-treated rats. Expression of ECP in activated eosinophils was associated with the presence of erosions and inflammation. The number of Ki-67-positive cells in the regenerated surface epithelium increased in anti-ECP-treated rats compared with normal serum-treated rats. Western blot analysis revealed reduced expression of macrophage migration inhibitory factor （MIF） in anti-ECP-treated rats. CONCLUSION： Our results indicate that treatment with ECP antibody, improved DSS-induced colitis in rats, possibly by increasing the regenerative activity of the colonic epithelium and downregulation of the immune response, and suggest that anti-ECP may promote intestinal wound healing in patients with ulcerative colitis （UC）.

关键词： Ulcerative colitis Eosinophil cationic protein dextran sulfate sodium

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Longitudinal analysis of inflammation and microbiota dynamics in a model of mild chronic dextran sulfate sodium-induced colitis in mice

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World Journal of Gastroenterology 2014年第8期20卷 2051-2061页

作者： Luigia De Fazio Elena Cavazza Enzo Spisni Antonio Strillacci Manuela Centanni Marco Candela Chiara Praticò Massimo Campieri Chiara Ricci Maria Chiara Valerii Department of Biological Geological and Environmental SciencesBiology UnitUniversity of BolognaVia Selmi 340126 BolognaItaly Department of Pharmacy and Biotechnology University of BolognaVia 640126 BolognaItaly Department of Medical and Surgical Sciences University of BolognaVia Massarenti 940138 BolognaItaly Department of Clinical and Experimental Sciences University of BresciaSpedali Civili 125121 BresciaItaly

AIM: To characterize longitudinally the inflammation and the gut microbiota dynamics in a mouse model of dextran sulfate sodium (DSS)-induced colitis.

关键词： Colitis, Dysbiosis dextran sulfate sodium Inflammation Cyclooxygenase 2

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sodium arsenite reduces severity of dextran sulfate sodium-induced ulcerative colitis in rats

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2008年第4期9卷 341-350页

作者： Joshua J. MALAGO Hortensia NONDOLI Department of Pathology Faculty of Veterinary Medicine Sokoine University of Agriculture P.O. Box 3203 Morogoro Tanzania Regional Immigration Office P.O. Box 649 Mtwara Tanzania

The histopathological features and the associated clinical findings of ulcerative colitis (UC) are due to persistent inflammatory response in the colon mucosa. Interventions that suppress this response benefit UC patients. We tested whether sodium arsenite (SA) benefits rats with dextran sulfate sodium (DSS)-colitis. The DSS-colitis was induced by 5% DSS in drinking water. SA (10 mg/kg; intraperitoneally) was given 8 h before DSS treatment and then every 48 h for 3 cycles of 7, 14 or 21 d. At the end of each cycle rats were sacrificed and colon sections processed for histological examination. DSS induced diarrhea, loose stools, hemoccult positive stools, gross bleeding, loss of body weight, loss of epithelium, crypt damage, depletion of goblet cells and infiltration of inflammatory cells. The severity of these changes increased in the order of Cycles 1, 2 and 3. Treatment of rats with SA significantly reduced this severity and improved the weight gain.

关键词： Ulcerative colitis dextran sulfate sodium sodium arsenite Rats

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Dramatic Changes of Matrix Metalloproteinases-7 and Lysozyme in the Ulcerative Colitis of Mice Induced by dextran sulfate sodium

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Journal of Integrative Agriculture 2014年第4期13卷 858-869页

作者： KANG Jing-jing ZHAO De-ming TENG Ke-dao JIAO Xi-lan WANG Ping-li SUN Zhe NI Pei-pei WANG Zhi-feng ZHANG Rui YANG Yu-rong LIANG Hong-de Pathology Laboratory College of Animal Husbandry and Veterinary Science Henan Agricultural University College of Animal Medicine China Agricultural University

Ulcerative colitis （UC） is a lifelong illness with profound emotional and social impacts, and could cause serious damage to large intestine, especially in colon. However, the pathogenesis of UC remained unclear. The present study attempts to find out the role of matrix metalloproteinases-7 （MMP-7） and lysozyme in the pathogenesis of UC through a mice model induced by dextran sulfate sodium （DSS）. The UC model was evaluated both by disease activity index （DAI） and the intestinal histopathology. The results show that there is a high correlation between the DAI score and the pathological changes of colon. Interleukin-6 （IL-6） serum levels and large intestinal fluids levels in UC mice are always higher than that of the control groups, which might be associated with the degree of the inflammation damage in the colon. The change tendency of the MMP-7 mRNA and protein expressions are both up-regulated firstly and then down-regulated from 1 to 5 d in the colon, but only the MMP-7 protein is up-regulated at 7 d again. The up-regulated MMP-7 levels in the early stage of UC may play a protective role through the activated defensins, while the down-regulated levels in the mid-later stage of UC may be connected with the severe lesions in the colon. However, the up-regulated MMP-7 levels in the later stage of UC in the colon may also contribute to the tissue repair or be served as a marker to CRC （colorectal cancer）. The distribution of lysozyme protein indicates that there may be Paneth-like cells in the colon. Both the changes of MMP-7 and lysozyme in the small intestine may play a protective role for the safe environment of the whole gut, especially to the colon of UC.

关键词： matrix metalloproteinases-7 lysozyme interleukin-6 ulcerative colitis dextran sulfate sodium

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Inhibitory Effect of Recombinant IL-25 on the Development of dextran sulfate sodium-Induced Experimental Colitis in Mice

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Cellular & Molecular Immunology 2008年第6期5卷 425-431页

作者： S.S. Salum Mchenga Department of Immunology College of Basic Medical Science China Medical University

The role of interleukin 25 （IL-25） in a number of human diseases still has not been extensively studied, here we attempt to evaluate the role of recombinant IL-25 （rIL-25） in the development of dextran sulfate sodium （DSS）- induced experimental colitis. Acute colitis was induced in female C57BL/6 mice by oral administration of 2.5% DSS in drinking water ad libitum. At the same time as the start of DSS exposure, mice were injected intraperitoneally with 0.4 ＋tg of rIL-25 or PBS. Then disease activity index （DAI）, histological changes and survival rate were observed. The levels of IL-17, IL-23, and TGF-β1 in colon tissues were determined by ELISA, and the production of IL-17 by CD4＋/CD8＋ T cells was detected by intracellular flow cytometry. In contrast to the DSS treated mice, DSS ＋ rIL-25 treated mice displayed a lower DAI, limited histological changes and prolonged survival. The levels of IL-23 and TGF-β1 were significantly elevated in the DSS ＋ rIL-25 treated mice compared to the DSS treated mice. There was no significant difference in the production of IL-17 in colon tissues and CD4＋/CD8＋ T cells between the DSS ＋ rIL-25 treated mice and DSS treated mice. Our findings suggest the role of IL-25 in inhibiting development and progression of acute colitis in DSS-induced mouse colitis model. Cellular ＆ Molecular Immunology. 2008;5（6）：425-431.

关键词： IL-25 dextran sulfate sodium disease activity index colitis

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Protective Effect of Total Alkaloids of Sophora Alopecuroides on dextran sulfate sodium-Induced Chronic Colitis

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Chinese Journal of Integrative Medicine 2011年第8期17卷 616-624页

作者：赵文昌宋丽军邓虹珠 School of Pharmacy Guangdong Medical College School of Traditional Chinese Medicine Southern Medical University

Objective：To investigate the effect of total alkaloids of Sophora alopecuroides（TASA） on dextran sulfate sodium（DSS）-induced colitis in ***：Chronic experimental colitis was induced by administration of 4 cycles of 4%*** mice were randomly distributed into 4 groups（normal,DSS,DSS/high-dose TASA, and DSS/low-dose TASA groups） by a random number table with body weight *** in the normal group（n=11） and DSS-induced colitis control group（n=15） received control treatment of 20 mL/kg distilled water; DSS plus TASA high- and low-dose groups（n=12 each） were treated with TASA solution（20 mL/kg） at the doses of 60 mg/kg and 30 mg/kg,*** severity of colitis was assessed on the basis of clinical signs, colon length,and histology ***,secretory immunoglobulin A（slgA） and haptoglobin（HP） were analyzed by enzyme linked immunosorbent assay;intercellular adhesion molecule 1（ICAM-1） and macrophage-migration inhibitory factor（MIF） gene expressions were analyzed by quantitative reverse transcriptase realtime polymerase chain reaction（qRT-PCR） using SYBA greenⅠ;and nuclear factorκB（NF-κB） expression and activation and p65 interaction with the promoter of ICAM-1 gene were assessed by Western blotting and chromatin immunoprecipitation ***：TASA administration significantly attenuated the damage and substantially reduced HP elevation and maintained the level of cecum *** inhibited the ICAM-1 gene expression and had no effect on MIF gene ***,TASA was able to reduce phospho-lκBα（p-lκBα） protein expression;however,it had no effect on the activation of IκB kinaseα（IKKα） and inhibitor of NF-κBα（IκBα）.Moreover,TASA inhibited the p65 recruitment to the ICAM-1 gene ***：TASA had a protective effect on DSS-induced *** effect may be associated with its inhibition of NF-κB activation and blockade of NF-κB-regulated transcription activation of proinflammatory mediator gene.

关键词： total alkaloids of Sophora alopecuroides dextran sulfate sodium colitis nuclear factorκB signal transduction pathway

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Protective effect of decursin and decursinol angelate-rich Angelica gigas Nakai extract on dextran sulfate sodium-induced murine ulcerative colitis

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Asian Pacific Journal of Tropical Medicine 2017年第9期10卷 864-870页

作者： Sa-Rang Oh Seon Ok Tae-Sung Jung Sang-Ok Jeon Ji-Min Park Ji-wook Jung Deok-Seon Ryu Department of Wellbeing Products Co. LtdGimhaeGyeongnam 50969Republic of Korea Department of Herbal Medicinal Pharmacology College of Herbal Bio-industryDaeguHaany UniversityKyungsanRepublic of Korea Department of Biomedical Laboratory Science College of Medical SciencesSoonchunhyang UniversityAsanRepublic of Korea

Objective: To investigate the anti-inflammatory effects of decursin and decursinol angelate-rich Angelica gigas Nakai(AGNE) on dextran sulfate sodium(DSS)-induced murine ulcerative colitis(UC).Methods: The therapeutic effect of an AGNE was analyzed in a mouse model of UC induced by DSS. Disease activity index values were measured by clinical signs such as a weight loss, stool consistency, rectal bleeding and colon length. A histological analysis was performed using hematoxylin and eosin staining. Key inflammatory cytokines and mediators including IL-6, TNF-a, PGE2, COX-2 and HIF-1 a were assayed by enzymelinked immunosorbent assay or western ***: Treatment with the AGNE at 10, 20, and 40 mg/kg alleviated weight loss,decreased disease activity index scores, and reduced colon shortening in mice with DSSinduced UC. AGNE inhibited the production of IL-6 and TNF-a in serum and colon tissue. Moreover, AGNE suppressed the increased expression of COX-2 and HIF-1 a and the increased production of PGE2 in colon tissue were observed in mice with DSSinduced UC. Additionally, histological damage was also alleviated by AGNE ***: The findings of this study verified that AGNE significantly improves clinical symptoms and reduces the activity of various inflammatory mediators. These results indicate the AGNE has the therapeutic potential in mice with DSS-induced UC.

关键词： Angelica gigas Nakai Ulcerative colitis dextran sulfate sodium Anti-inflammatory effects Cytokine

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Differential analysis of intestinal microbiota and metabolites in mice with dextran sulfate sodium-induced colitis

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World Journal of Gastroenterology 2022年第43期28卷 6109-6130页

作者： Jia-Li Wang Xiao Han Jun-Xiang Li Rui Shi Lei-Lei Liu Kai Wang Yu-Ting Liao Hui Jiang Yang Zhang Jun-Cong Hu Li-Ming Zhang Lei Shi Graduate School Beijing University of Chinese MedicineBeijing 100029China Department of Gastroenterology Dongfang HospitalBeijing University of Chinese MedicineBeijing 100078China College of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing 102488China Department of Emergency The First Teaching Hospital of Tianjin University of Traditional Chinese MedicineTianjin 300193China Department of Geriatrics Gulou Hospital of Traditional Chinese MedicineBeijing 100009China

BACKGROUND Intestinal micro-ecological imbalances impair the intestinal barrier and induce intestinal inflammation,for example,ulcerative colitis(UC).According to the latest research,abnormalities in intestinal microbiota structure and their metabolites play a dominant role in UC progression;in addition,they could affect the mucus barrier based on different *** numerous studies have confirmed the important role of intestinal microbiota in UC pathogenesis,the intricate connection between microbiota and metabolites and mucus barrier in UC occurrence remains unclear,and correlation analyses of differential microbiota and their metabolites under UC are relatively *** To reveal the differential intestinal microbiota and metabolites in UC pathogenesis and explore more sensitive biomarker *** We used the antibiotic combination method to establish intestinal pseudo-aseptic mice;afterward,dextran sulfate sodium(DSS)was applied to establish an acute experimental colitis mice *** severity,assessed based on disease activity index,colorectal length,colorectal wet weight,and histological lesions,and mucus-related staining(mucopolysaccharide alcian blue and immunofluorescence of mucin),was compared between the pseudo-aseptic and bacterial colitis ***,differential intestinal microbiota,metabolites,and their association and correlations,were analyzed by 16s rDNA sequencing in combination with non-targeted metabolomics,through gas chromatography-mass *** Compared with the pseudo-aseptic mice,intestinal bacteria positive mice were more severely ill and their intestinal mucus loss was more pronounced in DSS-induced colitis(P<0.05),suggesting that different microbiota and metabolites could cause the different degrees of ***,we observed that in addition to Klebsiella,and Bacteroides,which were widely associated with colitis,Candidatus Stoquefichus,Anaerobiospirillum,Muribaculum,and Negativibacillus

关键词： Ulcerative colitis Gut microbiota Metabolites dextran sulfate sodium Mucin

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