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姜黄素联合粪菌移植对DSS诱导的小鼠溃疡性结肠炎的改善作用
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作者 刘扬 路明 +1 位作者 洪文 黄克林 《吉林大学学报(医学版)》 CAS CSCD 北大核心 2024年第1期136-142,共7页
目的:探讨姜黄素联合粪菌移植对葡聚糖硫酸钠(DSS)诱导的小鼠溃疡性结肠炎(UC)的改善作用,并阐明其相关作用机制。方法:50只小鼠随机分为对照组、模型组、姜黄素组、粪菌移植组和联合组,除对照组小鼠自由饮用纯净水外,其余各组小鼠自由... 目的:探讨姜黄素联合粪菌移植对葡聚糖硫酸钠(DSS)诱导的小鼠溃疡性结肠炎(UC)的改善作用,并阐明其相关作用机制。方法:50只小鼠随机分为对照组、模型组、姜黄素组、粪菌移植组和联合组,除对照组小鼠自由饮用纯净水外,其余各组小鼠自由饮用含2%DSS的蒸馏水建立UC模型。姜黄素组小鼠灌胃给予60 mg·kg^(-1)姜黄素溶液0.4 mL,每日1次,连续10 d;粪菌移植组小鼠灌肠粪菌液0.2 mL,每日1次,持续10 d;联合组小鼠给予0.2 mL粪菌液灌肠后,给予60 mg·kg^(-1)姜黄素溶液0.4 mL灌胃。实验结束后,计算各组小鼠疾病活动指数(DAI)和结肠大体形态损伤指数(CDMI),HE染色观察各组小鼠结肠组织病理形态表现,酶联免疫吸附试验(ELISA)法检测各组小鼠结肠组织中白细胞介素(IL)-1β、肿瘤坏死因子α(TNF-α)、IL-4和IL-10水平,实时荧光定量PCR(RT-q PCR)法和Westernblotting法检测各组小鼠结肠组织中闭合蛋白(occludin)和闭锁小带蛋白1(ZO-1)m RNA及蛋白表达水平。结果:对照组小鼠结肠黏膜上皮结构完整且连续,腺体排列规则,无炎性细胞浸润和溃疡;模型组小鼠结肠黏膜上皮脱失,腺体排列紊乱,杯状细胞减少,黏膜和黏膜下层充血水肿,大量炎性细胞浸润,弥漫分布小溃疡;姜黄素组、粪菌移植组和联合组小鼠结肠黏膜上皮结构相对完整,炎性细胞浸润减少,黏膜和黏膜下层充血水肿减轻。与对照组比较,模型组小鼠DAI和CDMI升高(P<0.05),结肠组织中IL-1β和TNF-α水平升高(P<0.05),IL-4和IL-10水平降低(P<0.05),occludin和ZO-1 mRNA及蛋白表达水平降低(P<0.05);与模型组比较,姜黄素组、粪菌移植组和联合组小鼠DAI和CDMI降低(P<0.05),结肠组织中IL-1β和TNF-α水平降低(P<0.05),IL-4和IL-10水平升高(P<0.05),occludin和ZO-1mRNA及蛋白表达水平升高(P<0.05);与姜黄素组和粪菌移植组比较,联合组小鼠DAI和CDMI降低(P<0.05),结肠组织中IL-1β和TNF-α水平降低(P<0.05),IL-4和IL-10水平升高(P<0.05),occludin和ZO-1 mRNA及蛋白表达水平升高(P<0.05)。结论:姜黄素联合粪菌移植可改善UC小鼠结肠组织病理损伤,抑制炎症因子分泌,促进肠黏膜修复。 展开更多
关键词 溃疡性结肠炎 炎症因子 姜黄素 粪菌移植 葡聚糖硫酸钠
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Comprehensive analysis of sodium polystyrene sulfonate-induced colitis:A systematic review 被引量:1
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作者 Gabriel Peixoto Aver Guilherme Ferreira Ribeiro +5 位作者 Vinícius Remus Ballotin Francisco Souza dos Santos Lucas Goldmann Bigarella Floriano Riva Eduardo Brambilla Jonathan Soldera 《World Journal of Meta-Analysis》 2023年第7期351-367,共17页
BACKGROUND Sodium polystyrene sulfonate(SPS)is commonly prescribed for the management of hyperkalemia,a critical electrolyte imbalance contributing to over 800000 annual visits to emergency departments.AIM To conduct ... BACKGROUND Sodium polystyrene sulfonate(SPS)is commonly prescribed for the management of hyperkalemia,a critical electrolyte imbalance contributing to over 800000 annual visits to emergency departments.AIM To conduct a systematic review of documented cases of SPS-induced colitis and assess its associated prognosis.METHODS Following the PRISMA-P guidelines,our study employed Medical Subject Headings and Health Sciences Descriptors,skillfully combined using Boolean operators,to conduct comprehensive searches across various electronic databases,including Scopus,Web of Science,MEDLINE(PubMed),BIREME(Biblioteca Regional de Medicina),LILACS(Latin American and Caribbean Health Sciences Literature),SciELO(Scientific Electronic Library Online),Embase,and Opengray.eu.Language criteria were confined to English,Spanish,and Portuguese,with no limitations on the publication date.Additionally,we manually scrutinized the reference lists of retrieved studies.To present our findings,we utilized simple descriptive analysis.RESULTS Our search strategy yielded a total of 442 references.After rigorous evaluation,we included 51 references,encompassing 59 documented cases of colitis.Predominant clinical presentations included abdominal pain,observed in 35(60.3%)cases,and bloating,reported in 18(31%)cases.The most frequently affected sites of inflammation were the cecum,rectum,and small intestine,accounting for 31%,25.8%,and 22.4%of cases,respectively.Colonoscopy findings were described in 28(48.2%)cases,and 29(50%)of patients required surgical intervention.Among the subset of patients for whom outcome data was available,39(67.2%)experienced favorable outcomes,while 12(20.6%)unfortunately succumbed to the condition.The mean time required for resolution was 36.7 d,with a range spanning from 1 to 120 d.CONCLUSION SPS demonstrates the capacity to effectively lower serum potassium levels within 24 h.However,this benefit is not without the risk of bowel injury.Our study highlights the absence of high-quality data pertaining to the incidence of adverse events associated with SPS usage,making it challenging to determine whether the potential risks outweigh the benefits.However,a significant mortality rate related to SPS-induced colitis was noted.Future investigations should prioritize randomized controlled trials with a sufficiently large patient cohort to ascertain the true utility and safety profile of this medication. 展开更多
关键词 sodium polystyrene sulfonate HYPERKALEMIA colitis Bowel necrosis Kayexalate
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地黄多糖对DSS诱导的小鼠溃疡性结肠炎的治疗作用
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作者 吕弯弯 赵茂娇 +4 位作者 李科 冯仕红 文雨薇 秦雪梅 杜昱光 《山西医科大学学报》 CAS 2024年第7期863-871,共9页
目的探讨地黄多糖对葡聚糖硫酸钠(DSS)诱导的小鼠溃疡性结肠炎的治疗作用及机制。方法提取生、熟地黄水提物及多糖,并测定生、熟地黄多糖相对分子量及单糖组成。将70只ICR小鼠随机分为空白组、模型组(DSS组)、美沙拉嗪组(5-ASA组)、生... 目的探讨地黄多糖对葡聚糖硫酸钠(DSS)诱导的小鼠溃疡性结肠炎的治疗作用及机制。方法提取生、熟地黄水提物及多糖,并测定生、熟地黄多糖相对分子量及单糖组成。将70只ICR小鼠随机分为空白组、模型组(DSS组)、美沙拉嗪组(5-ASA组)、生地黄水提物组(RR组)、熟地黄水提物组(PR组)、生地黄多糖组(RRP组)、熟地黄多糖组(PRP组),每组10只。第1~7天,除空白组外,其余小鼠饮用3%的DSS;第8~14天,空白组和DSS组小鼠饮用无菌水,5-ASA组、RR组、RRP组、PR组和PRP组分别给予美沙拉嗪、生地黄水提物、生地黄多糖、熟地黄水提物及熟地黄多糖,给药剂量均为200 mg/kg。实验过程中每天记录小鼠的体质量、粪便硬度及直肠出血情况(疾病活动指数);测量小鼠结肠长度;采用HE染色法观察结肠组织病理形态变化;ELISA法测定结肠组织中髓过氧化物酶(MPO)活性及LPS水平。结果生、熟地黄多糖分子量均可分为约200 kD和4 kD。生地黄多糖由葡萄糖、半乳糖、半乳糖醛酸、甘露糖、鼠李糖、木糖、岩藻糖7种单糖所组成,熟地黄多糖由葡萄糖、半乳糖、半乳糖醛酸、甘露糖、木糖、岩藻糖6种单糖组成。与空白组相比,DSS组小鼠体质量明显下降(P<0.0001),DAI评分显著提高(P<0.0001),小鼠结肠长度缩短(P<0.05),脾脏质量增加(P<0.0001),结肠组织中MPO酶活性和血清中LPS含量升高(P<0.05)。与DSS组相比,5-ASA组、RR组、RRP组和PR组疾病活动指数显著下降(P<0.05);PRP组疾病活动指数评分最低(P<0.0001);PR组结肠长度显著增长(P<0.05);5-ASA组、RR组、PR组脾脏指数显著下降(P<0.01);多糖组(RRP和PRP组)下降最多(P<0.001);RR组、RRP组、PR组和PRP组结肠中MPO酶活性显著降低(P<0.05);PR组血清中LPS含量显著降低(P<0.05)。结论生、熟地黄多糖及水提物均能够改善结肠病理组织,且熟地黄水提物及多糖对结肠炎小鼠治疗效果较好。 展开更多
关键词 溃疡性结肠炎 地黄多糖 葡聚糖硫酸钠 小鼠 美沙拉嗪
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Differences in the effects and action modes of gut commensals against dextran sulfate sodium-induced intestinal inflammation
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作者 Dingwu Qu Zhennan Gu +5 位作者 Saisai Feng Leilei Yu Fengwei Tian Hao Zhang Wei Chen Qixiao Zhai 《Food Science and Human Wellness》 SCIE CSCD 2024年第3期1201-1211,共11页
Inflammatory bowel disease(IBD)is a complex relapsing inflammatory disease in the gut and is driven by complicated host-gut microbiome interactions.Gut commensals have shown different functions in IBD prevention and t... Inflammatory bowel disease(IBD)is a complex relapsing inflammatory disease in the gut and is driven by complicated host-gut microbiome interactions.Gut commensals have shown different functions in IBD prevention and treatment.To gain a mechanistic understanding of how different commensals affect intestinal inflammation,we compared the protective effects of 6 probiotics(belonging to the genera Akkermansia,Bifidobacterium,Clostridium,and Enterococcus)on dextran sulfate sodium(DSS)-induced colitis in mice with or without gut microbiota.Anti-inflammatory properties(ratio of interleukin(IL)-10 and IL-12)of these strains were also evaluated in an in vitro mesenteric lymph nodes(MLN)co-culture system.Results showed that 4 probiotics(belonging to the species Bifidobacterium breve,Bifidobacterium bifidum,and Enterococcus faecalis)can alleviate colitis in normal mice.The probiotic strains differed in regulating the intestinal microbiota,cytokines(IL-10,IL-1βand interferon(IFN)-γ),and tight junction function(Zonulin-1 and Occludin).By constrast,Akkermansia muciniphila AH39 and Clostridium butyricum FHuNHHMY49T1 were not protective.Interestingly,B.breve JSNJJNM2 with high anti-inflammatory potential in the MLN model could relieve colitis symptoms in antibiotic cocktail(Abx)-treated mice.Meanwhile,E.faecalis FJSWX25M1induced low levels of cytokines in vitro and showed no beneficial effects.Therefore,we provided insight into the clinical application of probiotics in IBD treatment. 展开更多
关键词 Gut commensals Dextran sulfate sodium(dss)colitis Intestinal barrier IMMUNOREGULATION
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Effect of Berberine Chloride on Experimental Murine Colitis Induced by Dextran Sulfate Sodium 被引量:5
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作者 舒德忠 万先惠 +2 位作者 刘华蓉 杨俊卿 周岐新 《Journal of Chinese Pharmaceutical Sciences》 CAS 2006年第3期182-187,共6页
Aim To investigate the effect in berberine chloride (BER) on experimental ulcerative colitis in mice. Methods BALB/C mice in 6 groups were allowed to drink either 4% dextran sulfate sodium (DSS) solution or distil... Aim To investigate the effect in berberine chloride (BER) on experimental ulcerative colitis in mice. Methods BALB/C mice in 6 groups were allowed to drink either 4% dextran sulfate sodium (DSS) solution or distilled water freely with different doses of BER (15 mg·kg^-1, 45 mg·kg^-1, 150 mg·kg^-1) or sallcylazosulfapyridine (SASP, 520 mg·kg^-1), and solvent (0. 2 mL/10 mg Wt) once a day for 7 d, respectively. The symptom of ulcerative colitis was evaluated by disease activity index (DAI). Myeloperoxidase (MPO) and superoxide dismutase (SOD) activities and malondialdehyde (MDA) content were determined by HE staining and immunohistochemistry of expressions of NF-κB p65 and intercellular adhesion molecule 1 ( ICAM-1 ) proteins to observe the damage to colon tissues and possible mechanisms. Results DAI, MPO activity, MDA content and expressions of ICAM-1 and NF-κB p65 were markedly increased, while SOD activity decreased in DSS-treated mice. Treatment of mice with different doses of BER or SASP significantly decreased DAI, MPO activity and MDA content, improved histological changes of colon tissues, blunted the expressions of NF-κB p65 and ICAM-1 proteins, and enhanced SOD activity. Conclusion Berberine chloride has excellent therapeutic effect on ulcerative colitis caused by DSS in mice. The possible mechanism may be related to its antioxidant and anti-inflammatory activities associated with inhibiting the NF-κB activation and ICAM-1 expression. 展开更多
关键词 berberine chloride ulcerative colitis dextran sulfate sodium BALB/C mice
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Dextran sodium sulfate colitis murine model: An indispensable tool for advancing our understanding of inflammatory bowel diseases pathogenesis 被引量:64
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作者 Derrick D Eichele Kusum K Kharbanda 《World Journal of Gastroenterology》 SCIE CAS 2017年第33期6016-6029,共14页
Inflammatory bowel diseases(IBD),including Crohn's disease and ulcerative colitis,are complex diseases that result from the chronic dysregulated immune response in the gastrointestinal tract. The exact etiology is... Inflammatory bowel diseases(IBD),including Crohn's disease and ulcerative colitis,are complex diseases that result from the chronic dysregulated immune response in the gastrointestinal tract. The exact etiology is not fully understood,but it is accepted that it occurs when an inappropriate aggressive inflammatory respon-se in a genetically susceptible host due to inciting environmental factors occurs. To investigate the path-ogenesis and etiology of human IBD,various animal models of IBD have been developed that provided indispensable insights into the histopathological and morphological changes as well as factors associated with the pathogenesis of IBD and evaluation of therapeutic options in the last few decades. The most widely used experimental model employs dextran sodium sulfate(DSS) to induce epithelial damage. The DSS colitis model in IBD research has advantages over other various chemically induced experimental models due to its rapidity,simplicity,reproducibility and controllability. In this manuscript,we review the newer publicized advances of research in murine colitis models that focus upon the disruption of the barrier function of the intestine,effects of mucin on the development of colitis,alterations found in microbial balance and resultant changes in the metabolome specifically in the DSS colitis murine model and its relation to the pathogenesis of IBD. 展开更多
关键词 Dextran sodium sulfate Experimental colitis Inflammatory bowel disease PATHOGENESIS Intestinal barrier
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Temporal clinical, proteomic, histological and cellular immune responses of dextran sulfate sodium-induced acute colitis 被引量:5
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作者 Natalia Schneider Nunes Saejeong Kim +4 位作者 Maggie Sundby Parwathy Chandran Scott Robert Burks Ana Helena Paz Joseph Alan Frank 《World Journal of Gastroenterology》 SCIE CAS 2018年第38期4341-4355,共15页
AIM To investigate the temporal clinical, proteomic, histological and cellular immune profiles of dextran sulfate sodium(DSS)-induced acute colitis.METHODS Acute colitis was induced in C57 BL/6 female mice by administ... AIM To investigate the temporal clinical, proteomic, histological and cellular immune profiles of dextran sulfate sodium(DSS)-induced acute colitis.METHODS Acute colitis was induced in C57 BL/6 female mice by administration of 1%, 2% or 3% DSS in drinking water for 7 d. Animals were monitored daily for weight loss, stool consistency and blood in the stool, while spleens and colons were harvested on day 8. A time course analysis was performed in mice ingesting 3% DSS, which included colon proteomics through multiplex assay, colon histological scoring by a blinded investigator, and immune response through flow cytometry or immunohistochemistry of the spleen, mesenteric lymph node and colon.RESULTS Progressive worsening of clinical colitis was observed with increasing DSS from 1% to 3%. In mice ingesting 3% DSS, colon shortening and increase in proinflammatory factors starting at day 3 was observed, with increased spleen weights at day 6 and day 8. This coincided with cellular infiltration in the colon from day 2 to day 8, with progressive accumulation of macrophages F4/80^+, T helper CD4^+(Th), T cytotoxic CD8^+(Tcyt) and T regulatory CD25^+(Treg) cells, and progressive changes in colonic pathology including destruction of crypts, loss of goblet cells and depletion of the epithelial barrier. Starting on day 4, mesenteric lymph node and/or spleen presented with lower levels of Treg, Th and Tcyt cells, suggesting an immune cell tropism to the gut. CONCLUSION These results demonstrate that the severity of experimental colitis is dependent on DSS concentration, correlated with clinical, proteomic, histological and cellular immune response on 3% DSS. 展开更多
关键词 ULCERATIVE colitis DEXTRAN sulfate sodium Proteomics Inflammatory BOWEL diseases Inflammation
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Kefir treatment ameliorates dextran sulfate sodium-induced colitis in rats 被引量:3
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作者 Altug Senol Mehmet Isler +4 位作者 Recep Sutcu Mete Akin Ebru Cakir Betul M Ceyhan M Cem Kockar 《World Journal of Gastroenterology》 SCIE CAS 2015年第46期13020-13029,共10页
AIM: To investigate the preventive effect of kefir on colitis induced with dextran sulfate sodium(DSS) in rats.METHODS: Twenty-four male Wistar-albino rats were randomized into four groups: normal control,kefircontrol... AIM: To investigate the preventive effect of kefir on colitis induced with dextran sulfate sodium(DSS) in rats.METHODS: Twenty-four male Wistar-albino rats were randomized into four groups: normal control,kefircontrol,colitis,and kefir-colitis groups. Rats in the normal and kefir-control groups were administered tap water as drinking water for 14 d. Rats in the colitis and kefir-colitis groups were administered a 3% DSS solution as drinking water for 8-14 d to induce colitis. Rats in the kefir-control and kefir-colitis groups were administered 5 m L kefir once a day for 14 d while rats in the normal control and colitis group were administered an identical volume of the placebo(skim milk) using an orogastric feeding tube. Clinical colitis was evaluated with reference to the disease activity index(DAI),based on daily weight loss,stool consistency,and presence of bleeding in feces. Rats were sacrificed on the 15 th day,blood specimens were collected,and colon tissues were rapidly removed. Levels of myeloperoxidase(MPO),tumor necrosisfactor(TNF)-α,interleukin(IL)-10,malondialdehyde,and inducible nitric oxide synthase(i NOS) were measured in colon tissue.RESULTS: The DAI was lower in the kefir-colitis group than in the colitis group(on the 3rd and 5th days of colitis induction; P < 0.01). The DAI was also significantly higher in the colitis group between days 2 and 6 of colitis induction when compared to the normal control and kefir-control groups. The DAI was statistically higher only on the 6th day in the kefircolitis group when compared to that in the normal control groups. Increased colon weight and decreased colon length were observed in colitis-induced rats. Mean colon length in the colitis group was significantly shorter than that of the kefir-control group. Kefir treatment significantly decreased histologic colitis scores(P < 0.05). MPO activity in the colitis group was significantly higher than in the kefir-control group(P < 0.05). Kefir treatment significantly reduced the DSS colitis-induced TNF-α increase(P < 0.01). No statistically significant differences were observed among groups for IL-10 and MDA levels. Colon tissue i NOS levels in the colitis group were significantly higher than those in the control and kefir-colitis groups(P < 0.05).CONCLUSION: Kefir reduces the clinical DAI and histologic colitis scores in a DSS-induced colitis model,possibly via reduction of MPO,TNF-α,and i NOS levels. 展开更多
关键词 colitis DEXTRAN SULFATE sodium INFLAMMATORY BOWEL
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Protective effects of panax notoginseng saponin on dextran sulfate sodium-induced colitis in rats through phosphoinositide-3-kinase protein kinase B signaling pathway inhibition 被引量:5
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作者 Qing-Ge Lu Li Zeng +4 位作者 Xiao-Hai Li Yu Liu Xue-Feng Du Guo-Min Bai Xin Yan 《World Journal of Gastroenterology》 SCIE CAS 2020年第11期1156-1171,共16页
BACKGROUND Intestinal inflammation is a common digestive tract disease, which is usually treated with hormone medicines. Hormone medicines are effective to some extent, but long-term use of them may bring about many c... BACKGROUND Intestinal inflammation is a common digestive tract disease, which is usually treated with hormone medicines. Hormone medicines are effective to some extent, but long-term use of them may bring about many complications.AIM To explore the protective effects of panax notoginseng saponin(PNS) against dextran sulfate sodium(DSS)-induced intestinal inflammatory injury through phosphoinositide-3-kinase protein kinase B(PI3K/AKT) signaling pathway inhibition in rats.METHODS Colitis rat models were generated via DSS induction, and rats were divided into control(no modeling), DSS, DSS + PNS 50 mg/k, and DSS + PNS 100 mg/kg groups. Then, the intestinal injury, oxidative stress parameters, inflammatory indices, tight junction proteins, apoptosis, macrophage polarization, and TLR4/AKT signaling pathway in colon tissues from rats in each of the groups were detected. The PI3 K/AKT signaling pathway in the colon tissue of rats was blocked using the PI3K/AKT signaling pathway inhibitor, LY294002.RESULTS Compared with rats in the control group, rats in the DSS group showed significantly shortened colon lengths, and significantly increased disease activity indices, oxidative stress reactions and inflammatory indices, as well as significantly decreased expression of tight junction-associated proteins. In addition, the DSS group showed significantly increased apoptotic cell numbers,and showed significantly increased M1 macrophages in spleen and colon tissues.They also showed significantly decreased M2 macrophages in colon tissues, as well as activation of the PI3K/AKT signaling pathway(all P < 0.05). Compared with rats in the DSS group, rats in the DSS + PNS group showed significantly lengthened colon lengths, decreased disease activity indices, and significantly alleviated oxidative stress reactions and inflammatory responses. In addition, this group showed significantly increased expression of tight junction-associated proteins, significantly decreased apoptotic cell numbers, and significantly decreased M1 macrophages in spleen and colon tissues. This group further showed significantly increased M2 macrophages in colon tissues, and significantly suppressed activation of the PI3K/AKT signaling pathway, as well as a dose dependency(all P < 0.05). When the PI3K/AKT signaling pathway was inhibited, the apoptosis rate of colon tissue cells in the DSS + LY294002 group was significantly lower than that of the DSS group(P < 0.05).CONCLUSION PNS can protect rats against DSS-induced intestinal inflammatory injury by inhibiting the PI3K/AKT signaling pathway, and therefore may be potentially used in the future as a drug for colitis. 展开更多
关键词 Panax notoginseng SAPONIN Phosphoinositide-3-kinase protein KINASE B signaling pathway Dextran sulfate sodium colitis Rat intestine Protective effect
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Dextran sulfate sodium-induced acute colitis impairs dermal lymphatic function in mice 被引量:2
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作者 Germaine D Agollah Grace Wu +1 位作者 Ho-Lan Peng Sunkuk Kwon 《World Journal of Gastroenterology》 SCIE CAS 2015年第45期12767-12777,共11页
AIM: To investigate whether dermal lymphatic function and architecture are systemically altered in dextran sulfate sodium(DSS)-induced acute colitis.METHODS: Balb/c mice were administered 4% DSS in lieu of drinking wa... AIM: To investigate whether dermal lymphatic function and architecture are systemically altered in dextran sulfate sodium(DSS)-induced acute colitis.METHODS: Balb/c mice were administered 4% DSS in lieu of drinking water ad libitum for 7 d and monitored to assess disease activity including body weight, diarrhea severity, and fecal bleeding. Control mice received standard drinking water with no DSS. Changes in mesenteric lymphatics were assessed following oral administration of a fluorescently-labelled fatty acid analogue, while dermal lymphatic function and architecture was longitudinally characterized using dynamic near-infrared fluorescence(NIRF) imaging following intradermal injection of indocyanine green(ICG) at the base of the tail or to the dorsal aspect of the left paw prior to, 4, and 7 d after DSSadministration. We also measured dye clearance rate after injection of Alexa680-bovine serum albumin(BSA). NIRF imaging data was analyzed to reveal lymphatic contractile activity after selecting fixed regions of interest(ROIs) of the same size in fluorescent lymphatic vessels on fluorescence images. The averaged fluorescence intensity within the ROI of each fluorescence image was plotted as a function of imaging time and the lymphatic contraction frequency was computed by assessing the number of fluorescent pulses arriving at a ROI. RESULTS: Mice treated with DSS developed acute inflammation with clinical symptoms of loss of body weight, loose feces/watery diarrhea, and fecal blood, all of which were aggravated as disease progressed to 7 d. Histological examination of colons of DSS-treated mice confirmed acute inflammation, characterized by segmental to complete loss of colonic mucosa with an associated chronic inflammatory cell infiltrate that extended into the deeper layers of the wall of the colon, compared to control mice. In situ intravital imaging revealed that mice with acute colitis showed significantly fewer fluorescent mesenteric lymphatic vessels, indicating impaired uptake of a lipid tracer within mesenteric lymphatics. Our in vivo NIRF imaging data demonstrated dilated dermal lymphatic vessels, which were confirmed by immunohistochemical staining of lymphatic vessels, and significantly reduced lymphatic contractile function in the skin of mice with DSS-induced acute colitis. Quantification of the fluorescent intensity remaining in the depot as a function of time showed that there was significantly higher Alexa680-BSA fluorescence in mice with DSSinduced acute colitis compared to pre-treatment with DSS, indicative of impaired lymphatic drainage.CONCLUSION: The lymphatics are locally and systemically altered in acute colitis, and functional NIRF imaging is useful for noninvasively monitoring systemic lymphatic changes during inflammation. 展开更多
关键词 DEXTRAN SULFATE sodium colitis LYMPHATIC system In
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Sodium selenite ameliorates dextran sulfate sodiuminduced chronic colitis in mice by decreasing Th1, Th17, and γδT and increasing CD4(+)CD25(+) regulatory T-cell responses 被引量:3
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作者 Li-Xuan Sang Bing Chang +6 位作者 Jun-Feng Zhu Fang-Li Yang Yan Li Xue-Feng Jiang Da-Nan Wang Chang-Long Lu Xun Sun 《World Journal of Gastroenterology》 SCIE CAS 2017年第21期3850-3863,共14页
AIM To assess the effect of sodium selenite on the severity of dextran sulfate sodium(DSS)-induced colitis in C57BL/6 mice.METHODS Mice were randomly divided into four groups(n = 10/group): normal group, selenium(Se) ... AIM To assess the effect of sodium selenite on the severity of dextran sulfate sodium(DSS)-induced colitis in C57BL/6 mice.METHODS Mice were randomly divided into four groups(n = 10/group): normal group, selenium(Se) group, chronic colitis group, and Se + chronic colitis group. The mice were sacrificed on day 26. Survival rates, clinical symptoms, colon length, and histological changes were determined. The percentages and absolute numbers of immune system cells in the lamina propria lymphocytes(LPL) of the colon, the expression of m RNA in colon tissue, and the concentrations of Th1, Th17, and Treg cytokines in LPL from the large intestine, were measured.RESULTS Se significantly ameliorated the symptoms of colitis and histological injury(P < 0.05 each), increasing the proportions of neutrophils and CD4+ CD25+ T cells(P < 0.05 each) and decreasing the proportions of γδT cells, CD4+, CD4+CD44+, and CD4+ CD69+ T cells in LPL(P < 0.05 each). Moreover, Se reduced the expression of IL-6, IFN-γ, IL-17 A, IL-21, T-bet, and RORγt(P < 0.05 each), but enhanced the expression of IL-10 and Foxp3(P < 0.05 each). CONCLUSION These results suggest that Se protects against DSSinduced chronic colitis perhaps by increasing the number of CD4(+)CD25(+) Tregs that suppress the secretion of proinflammatory cytokines and populations of Th1, Th17, and γδT cells. 展开更多
关键词 sodium selenite Dextran sulfate sodium Chronic colitis
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Involvement of lymphocytes in dextran sulfate sodium-induced experimental colitis 被引量:6
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作者 Tae Woon Kim Jae Nam Seo +4 位作者 Young Ho Suh Hyo Jin Park Ju Hyun Kim Ji Young Kim Kwon Ik Oh 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第2期302-305,共4页
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 a... 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. 展开更多
关键词 Dextran sulfate sodium colitis LYMPHOCYTE Rag-1 KNOCKOUT
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Attenuation of dextran sodium sulphate induced colitis in matrix metalloproteinase-9 deficient mice 被引量:9
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作者 Alfredo Santana Carlos Medina +5 位作者 Maria Cristina Paz-Cabrera Federico Díaz-Gonzalez Esther Farré Antonio Salas Marek W Radomski Enrique Quintero 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第40期6464-6472,共9页
AIM: To study whether matrix metalloproteinase-9 (MMP-9) is a key factor in epithelial damage in the dextran sodium sulphate (DSS) model of colitis in mice.METHODS: MMP-9-deficient and wild-type (wt) mice were given 5... AIM: To study whether matrix metalloproteinase-9 (MMP-9) is a key factor in epithelial damage in the dextran sodium sulphate (DSS) model of colitis in mice.METHODS: MMP-9-deficient and wild-type (wt) mice were given 5% DSS in drinking water for 5 d followed by recovery up to 7 d. On d 5 and 12 after induction of colitis, gelatinases, MMP-2 and MMP-9, were measured in homogenates of colonic tissue by zymography and Western blot, whereas tissue inhibitor of metalloproteinases (TIMPs) were measured by reverse zymography. The gelatinolytic activity was also determined in supernatants of polymorphonuclear leukocytes (PMN) isolated from mice blood. Moreover, intestinal epithelial cells were stimulated with TNF-α to study whether these cells were able to produce MMPs. Finally, colonic mucosal lesions were measured by microscopic examination. RESULTS: On d 5 of colitis, the activity of MMP-9 was increased in homogenates of colonic tissues (0.24 ± 0.1 vs 21.3 ± 6.4, P < 0.05) and PMN from peripheral blood in wt (0.5 ± 0.1 vs 10.4 ± 0.7, P < 0.05), but not in MMP-9-deficient animals. The MMP-9 activity was also up-regulated by TNF-α in epithelial intestinal cells (2.5 ± 0.5 vs 14.7 ± 3.0, P < 0.05). Although colitis also led to increase of TIMP-1 activity, the MMP-9/TIMP-1 balance remained elevated. Finally, in the MMP-9-deficient colitic mice both the extent and severity of intestinal epithelialinjury were significantly attenuated when compared with wt mice. CONCLUSION: We conclude that DSS induced colitis is markedly attenuated in animals lacking MMP-9. This suggests that intestinal injury induced by DSS is modu-lated by MMP-9 and that inhibition of this gelatinase may reduce inflammation. 展开更多
关键词 Matrix metalloproteinases MMP-9-deficient Dextran sodium sulphate Inflammatory bowel disease Experimental colitis
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Induction of experimental acute ulcerative colitis in rats by administration of dextran sulfate sodium at low concentration followed by intracolonic administration of 30% ethanol 被引量:4
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作者 CHEN Yan SI Jian-min +4 位作者 LIU Wei-li CAI Jian-ting DU Qin WANG Liang-jing GAO Min 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2007年第9期632-637,共6页
Several models of experimental ulcerative colitis have been reported previously. However, none of these models showed the optimum characteristics. Although dextran sulfate sodium-induced colitis results in inflammatio... Several models of experimental ulcerative colitis have been reported previously. However, none of these models showed the optimum characteristics. Although dextran sulfate sodium-induced colitis results in inflammation resembling ulcera-tive colitis, an obvious obstacle is that dextran sulfate sodium is very expensive. The aim of this study was to develop an inex-pensive model of colitis in rats. Sprague-Dawley rats were treated with 2% dextran sulfate sodium in drinking water for 3 d fol-lowed by an intracolonic administration of 30% ethanol. The administration of 2% dextran sulfate sodium followed by 30% ethanol induced significant weight loss, diarrhea and hematochezia in rats. Severe ulceration and inflammation of the distal part of rat colon were developed rapidly. Histological examination showed increased infiltration of polymorphonuclear leukocytes, lymphocytes and existence of cryptic abscesses and dysplasia. The model induced by dextran sulfate sodium at lower concentra-tion followed by 30% ethanol is characterized by a clinical course, localization of the lesions and histopathological features similar to human ulcerative colitis and fulfills the criteria set out at the beginning of this study. 展开更多
关键词 Model colitis Dextran sulfate sodium ETHANOL
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Protective effect of decursin and decursinol angelate-rich Angelica gigas Nakai extract on dextran sulfate sodium-induced murine ulcerative colitis 被引量:5
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作者 Sa-Rang Oh Seon Ok +4 位作者 Tae-Sung Jung Sang-Ok Jeon Ji-Min Park Ji-wook Jung Deok-Seon Ryu 《Asian Pacific Journal of Tropical Medicine》 SCIE CAS 2017年第9期864-870,共7页
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... 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 blotting.Results: 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 treatment.Conclusions: 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. 展开更多
关键词 Angelica gigas Nakai Ulcerative colitis Dextran sulfate sodium Anti-inflammatory effects CYTOKINE
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Longitudinal analysis of inflammation and microbiota dynamics in a model of mild chronic dextran sulfate sodium-induced colitis in mice 被引量:2
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作者 Luigia De Fazio Elena Cavazza +7 位作者 Enzo Spisni Antonio Strillacci Manuela Centanni Marco Candela Chiara Praticò Massimo Campieri Chiara Ricci Maria Chiara Valerii 《World Journal of Gastroenterology》 SCIE CAS 2014年第8期2051-2061,共11页
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 被引量:3
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作者 Joshua J. MALAGO Hortensia NONDOLI 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2008年第4期341-350,共10页
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 pati... 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. 展开更多
关键词 Ulcerative colitis Dextran sulfate sodium sodium arsenite RATS
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Calcitriol analog ZK191784 ameliorates acute and chronic dextran sodium sulfate-induced colitis by modulation of intestinal dendritic cell numbers and phenotype 被引量:4
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作者 Ulrike G Strauch Florian Obermeier +6 位作者 Nicole Grunwald Nadja Dunger Heiko C Rath Jürgen Schlmerich A Steinmeyer U Zügel HH Herfarth 《World Journal of Gastroenterology》 SCIE CAS CSCD 2007年第48期6529-6537,共9页
AIM: To investigate the effects of ZK1916784, a low calcemic analog of calcitriol on intestinal inflammation. METHODS: Acute and chronic colitis was induced by dextran sodium sulfate (DSS) according to standard proced... AIM: To investigate the effects of ZK1916784, a low calcemic analog of calcitriol on intestinal inflammation. METHODS: Acute and chronic colitis was induced by dextran sodium sulfate (DSS) according to standard procedures. Mice were treated intraperitoneally with ZK1916784 or placebo and colonic inflammation was evaluated. Cytokine production by mesenterial lymph node (MLN) cells was measured by ELISA. Immunohistochemistry was performed to detect intestinal dendritic cells (DCs) within the colonic tissue, and the effect of the calcitriol analog on DCs was investigated. RESULTS: Treatment with ZK191784 resulted in significant amelioration of disease with a reduced histological score in acute and chronic intestinal inflammation. In animals with acute DSS colitis, down- regulation of colonic inflammation was associated with a dramatic reduction in the secretion of the proinflammatory cytokine interferon (IFN)-γ and a significant increase in intereleukin (IL)-10 by MLN cells. Similarly, in chronic colitis, IL-10 expression in colonic tissue increased 1.4-fold when mice were treated with ZK191784, whereas expression of the Th1-specific transcription factor T-beta decreased by 81.6%. Lower numbers of infiltrating activated CD11c+ DCs were found in the colon in ZK191784-treated mice with acute DSScolitis, and secretion of proinflammatory cytokines by primary mucosal DCs was inhibited in the presence of the calcitriol analog. CONCLUSION: The calcitriol analog ZK191784 demonstrated significant anti-inflammatory properties in experimental colitis that were at least partially mediated by the immunosuppressive effects of the derivate on mucosal DCs. 展开更多
关键词 Dextran sodium sulfate colitis CALCITRIOL Colonic inflammation Dendritic cells
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Anti-tumor necrosis factor α therapy associates to type 17 helper T lymphocytes immunological shift and significant microbial changes in dextran sodium sulphate colitis 被引量:2
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作者 Valentina Petito Cristina Graziani +13 位作者 Loris R Lopetuso Marco Fossati Alessandra Battaglia Vincenzo Arena Domenico Scannone Gianluca Quaranta Andrea Quagliariello Federica Del Chierico Lorenza Putignani Luca Masucci Maurizio Sanguinetti Alessandro Sgambato Antonio Gasbarrini Franco Scaldaferri 《World Journal of Gastroenterology》 SCIE CAS 2019年第12期1465-1477,共13页
BACKGROUND Anti-tumor necrosis factor α(TNFα) represents the best therapeutic option to induce mucosal healing and clinical remission in patients with moderate-severe ulcerative colitis. On the other side gut microb... BACKGROUND Anti-tumor necrosis factor α(TNFα) represents the best therapeutic option to induce mucosal healing and clinical remission in patients with moderate-severe ulcerative colitis. On the other side gut microbiota plays a crucial role in pathogenesis of ulcerative colitis but few information exists on how microbiota changes following anti-TNFα therapy and on microbiota role in mucosal healing.AIM To elucidate whether gut microbiota and immune system changes appear following anti TNFα therapy during dextran sulfate sodium(DSS) colitis.METHODS Eighty C57 BL/6 mice were divided into four groups: "No DSS", "No DSS + antiTNFα", "DSS" and "DSS + anti-TNFα". "DSS" and "DSS + anti-TNFα" were treated for 5 d with 3% DSS. At day 3, mice whithin "No DSS+anti-TNFα" and"DSS+anti-TNFα" group received 5 mg/kg of an anti-TNFα agent. Forty mice were sacrificed at day 5, forty at day 12, after one week of recovery post DSS. The severity of colitis was assessed by a clinical score(Disease Activity Index), colon length and histology. Bacteria such as Bacteroides, Clostridiaceae, Enterococcaceae and Fecalibacterium prausnitzii(F. prausnitzii) were evaluated by quantitative PCR.Type 1 helper T lymphocytes(Th1), type 17 helper T lymphocytes(Th17) and CD4+ regulatory T lymphocytes(Treg) distributions in the mesenteric lymph node(MLN) were studied by flow cytometry.RESULTS Bacteria associated with a healthy state(i.e., such as Bacteroides, Clostridiaceae and F. prausnitzii) decreased during colitis and increased in course of anti-TNFαtreatment. Conversely, microorganisms belonging to Enterococcaceae genera,which are linked to inflammatory processes, showed an opposite trend.Furthermore, in colitic mice treated with anti-TNFα microbial changes were associated with an initial increase(day 5 of the colitis) in Treg cells and a consequent decrease(day 12 post DSS) in Th1 and Th17 frequency cells. Healthy mice treated with anti-TNFα showed the same histological, microbial and immune features of untreated colitic mice. "No DSS + anti-TNFα" group showed a lymphomononuclear infiltrate both at 5 th and 12 th d at hematoxylin and eosin staining, an increase of in Th1 and Th17 frequency at day 12, an increase of Enterococcaceae at day 5, a decrease of Bacteroides and Clostridiaceae at day 12.CONCLUSION Anti-TNFα treatment in experimental model of colitis improves disease activity but it is associated to an increase in Th17 pathway together with gut microbiota alteration. 展开更多
关键词 Gut microbiota DEXTRAN sodium sulphate colitis Immune system T cells MESENCHYMAL lymphnode Tumor NECROSIS factor α
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Lactobacillus crispatus M206119 exacerbates murine DSS-colitis by interfering with inflammatory responses 被引量:3
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作者 Fu-Xi Zhou Lu Chen +5 位作者 Xiao-Wei Liu Chun-Hui Ouyang Xiao-Ping Wu Xue-Hong Wang Chun-Lian Wang Fang-Gen Lu 《World Journal of Gastroenterology》 SCIE CAS CSCD 2012年第19期2344-2356,共13页
AIM: TO investigate the role of Lactobacillus crispatus (L. crispatus) strain China Center for Type Culture Col- lection (CCTCC) M206119 in intestinal inflammation.METHODS: Forty 8-wk-old Balb/c mice (20± ... AIM: TO investigate the role of Lactobacillus crispatus (L. crispatus) strain China Center for Type Culture Col- lection (CCTCC) M206119 in intestinal inflammation.METHODS: Forty 8-wk-old Balb/c mice (20± 2 g) were divided into four groups of 10 mice each. Three groups that had received dextran sulfate sodium (DSS) were administered normal saline, sulfasalazine or CCTCC M206119 strain, and the fourth group received none of these. We assessed the severity of colitis using a disease activity index, measured the colon length and weight, collected stools and mesenteric lymph nodes for bacterial microflora analysis. One centimeter of the proximal colon, middle colon and distal colon were collected and fixed in 10% buffered formalin, dehydrated in ethanol, and embedded in paraffin. Interleukin (IL)- 1β, IL-6 and tumor necrosis factor (TNF)-α expression was detected using reverse transcription polymerase chain reaction. Protective factors zonula occludens (ZO)-1 and β-defensin 2 were detected by immunoblot-ting. The features of CCTCC M206119 strain were identified based on morphology, biochemical profile, and 16S RNA sequencing.RESULTS: DSS-colitis animals treated with CCTCC M206119 had markedly more severe disease, with greater weight loss, diarrhea, fecal bleeding, and shortened colon length. In addition, the CCTCC-M206119- treated group had comparatively higher histologi- cal scores and more neutrophil infiltration than the controls. Expression of protective factors ZO-1 and β-defensin 2 was downregulated due to destruction of the mucosal barrier after CCTCC M206119 strain treatment. An in vitro assay demonstrated that CCTCC M206119 strain increased the nuclear translocation of nuclear factor-κB in epithelial cells. Intestinal proinflam- matory or anti-inflammatory cytokine responses were evaluated. Proinflammatory colonic cytokine (IL-Iβ, IL-6 and TNF-α) levels were clearly increased in CCTCC- M206119-treated animals, whereas anti-inflammatory colonic cytokine (IL-10) level was lowered compared with saline or 5-aminosalicylic-acid-treated DSS-colitis mice. Next, CCTCC M206119 strain was characterized as 1. crispatus by microscopic morphology, biochemical tests and 16S rRNA gene level.CONCLUSION: Not all lactobacilli are beneficial for in- testinal inflammation, and L. crispatus CCTCC M206119 strain is involved in exacerbation of intestinal inflamma- tion in DSS-colitis mice. 展开更多
关键词 colitis Lactobacillus crispatus INTESTINE Dextra sodium sulfate MICE
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