Effect of chitosan on dextran sulfate sodium sulfate-induced ulcerative colitis in mice
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摘要: [目的]本研究旨在探讨壳聚糖对葡聚糖硫酸钠(Dextran sulfate sodium,DSS)诱导急性结肠炎小鼠的疗效和可能机制。[方法]选取Balb/c小鼠40只,随机分为正常对照组、DSS组、美沙拉嗪组及壳聚糖组,除正常组自由饮食外,其余组连续饮用3%DSS溶液7 d诱发急性结肠炎,建立溃疡性结肠炎模型,同时分别给予相应药物灌胃治疗,治疗期间每天观察小鼠的体重、粪便性状和血便情况,造模结束后检测结肠组织中性细胞髓过氧化物酶活力(myeloperoxidase,MPO)。[结果]DSS成功诱发急性结肠炎,小鼠有明显腹泻,粘液脓血便,体重减轻等。壳聚糖能有效改善DSS诱导的溃疡性结肠炎症状,降低结肠MPO活性(6.108±1.893 U/g:3.502±0.529 U/g,P<0.01);增加结肠长度,且HE染色的炎症程度和疾病活动指数均有明显改善。[结论]壳聚糖能有效治疗DSS诱发的急性结肠炎,主要通过诱导特异性免疫应答,降低炎症反应,增强机体免疫反应。未来有望成为治疗溃疡性结肠炎的潜在药物。
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关键词:
- 壳聚糖 /
- 免疫调节 /
- DSS诱导的溃疡性结肠炎 /
- 治疗
Abstract: [Objective]To investigate the effect of chitosan on acute inflammatory response in mice dextran sulfate sodium-induced colitis,and the potential mechanism.[Methods]Forty Balb/c mice were divided into four groups,including normal control,DSS,Chitosan and 5-ASA,randomly.The mice in DSS,5-ASA and Chitosan groups were orally administered with 3% DSS solution for 7 days to induce acute colitis,constructing ulcerative colitis model.During the experimental period,the mice were given corresponding drug lavage treatment.Clinical signs,body weight,stool consistency and fecal blood were observed every day.At the end of the experiment,the colonic myeloperoxidase(MPO)activity were measured.[Results]3%DSS successfully induced acute colitis associated with diarrhea,mucopurulent bloody stool,and body weight decreasing.Chitosan effectively improved the symptoms of UC induced by DSS,and reduced MPO activity in colonic tissue(6.108±1.893 U/g vs 3.502±0.529 U/g,P<0.01),increased the colon length.And the HE staining of the degree of inflammation and disease activity index were significantly improved.[Conclusion]Chitosan can effectively treat DSS-induced acute colitis through the induction of specific immune response,reducing the inflammatory response and enhancing the immune response.The Chitosan is expected to be a potential drug for the treatment of ulcerative colitis.-
Key words:
- immunomodulation /
- DSS-induced ulcerative colitis /
- treatment /
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[1] Adams S M, Bornemann P H.Ulcerative colitis[J].Am Fam Physician, 2013, 87 (10):699-705.
[2] Xavier R J, Podolsky D K.Unravelling the pathogenesis of inflammatory bowel disease[J].Nature, 2007, 448 (7152):427-434.
[3] Actis G C, Pellicano R, Rosina F.Inflammatory bowel disease:Traditional knowledge holds the seeds for the future[J].World J Gastrointest Pharmacol Ther, 2015, 6 (2):10-16.
[4] Becker C, Watson A J, Neurath M F.Complex roles of caspases in the pathogenesis of inflammatory bowel disease[J].Gastroenterology, 2013, 144 (2):283-293.
[5] MacDonald T T, Biancheri P, Sarra M, et al.What's the next best cytokine target in IBD?[J].Inflamm Bowel Dis, 2012, 18 (11):2180-2189.
[6] Chadwick S, Kriegel C, Amiji M.Nanotechnology solutions for mucosal immunization[J].Adv Drug Deliv Rev, 2010, 62 (4-5):394-407.
[7] Azuma K, Osaki T, Minami S, et al.Anticancer and anti-inflammatory properties of chitin and chitosan oligosaccharides[J].J Funct Biomater, 2015, 6 (1):33-49.
[8] Westerink M A, Smithson S L, Srivastava N, et al.ProJuvant (Pluronic F127/chitosan) enhances the immune response to intranasally administered tetanus toxoid[J].Vaccine, 2001, 20 (5-6):711-723.
[9] Cooper H S, Murthy S N, Shah R S, et al.Clinicopathologic study of dextran sulfate sodium experimental murine colitis[J].Lab Invest, 1993, 69 (2):238-249.
[10] Takagi T, Naito Y, Uchiyama K, et al.Carbon monoxide liberated from carbon monoxide-releasing molecule exerts an anti-inflammatory effect on dextran sulfate sodium-induced colitis in mice[J].Dig Dis Sci, 2011, 56 (6):1663-1671.
[11] Jarmila V, Vavrikova E.Chitosan derivatives with antimicrobial, antitumour and antioxidant activities——a review[J].Curr Pharm Des, 2011, 17 (32):3596-3607.
[12] Yoon H J, Moon M E, Park H S, et al.Chitosan oligosaccharide (COS) inhibits LPS-induced inflammatory effects in RAW 264.7 macrophage cells[J].Biochem Biophys Res Commun, 2007, 358 (3):954-959.
[13] 彭亮, 赵鹏, 李彬, 等.壳聚糖对小鼠免疫调节作用的实验研究[J].实用预防医学, 2014 (9):1126-1128.
[14] Li Y, Liu H, Xu Q S, et al.Chitosan oligosaccharides block LPS-induced O-GlcNAcylation of NF-kappaB and endothelial inflammatory response[J].Carbohydr Polym, 2014, 99:568-578.
[15] Chen Y L, Wang C Y, Yang F Y, et al.Synergistic effects of glycated chitosan with high-intensity focused ultrasound on suppression of metastases in a syngeneic breast tumor model[J].Cell Death Dis, 2014, 5 (4):e1178.
[16] Yousef M, Pichyangkura R, Soodvilai S, et al.Chitosan oligosaccharide as potential therapy of inflammatory bowel disease:therapeutic efficacy and possible mechanisms of action[J].Pharmacol Res, 2012, 66 (1):66-79.
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