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Efficacy of Topical versus Oral 5-Aminosalicylate for Treatment of 2,4,6-Trinitrobenzene Sulfonic Acid-induced Ulcerative Colitis in Rats 被引量:3
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作者 李进 陈成 +3 位作者 曹小年 王桂华 胡俊波 王晶 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2014年第1期59-65,共7页
5-aminosalicylic acid(5-ASA) is drug of choice for the treatment of ulcerative colitis(UC). In this study, the efficacy of topical versus oral 5-ASA for the treatment of UC was examined as well as the action mecha... 5-aminosalicylic acid(5-ASA) is drug of choice for the treatment of ulcerative colitis(UC). In this study, the efficacy of topical versus oral 5-ASA for the treatment of UC was examined as well as the action mechanism of this medication. A flexible tube was inserted into the rat cecum to establish a topical administration model of 2,4,6-trinitrobenzene sulfonic acid(TNBS)-induced UC. A total of 60 rats were divided into sham operation group(receiving an enema of 0.9% saline solution instead of the TNBS solution via the tube), model group, topical 5-ASA group, oral Etiasa group(a release agent of mesalazine used as positive control) and oral 5-ASA group(n=12 each). Different treatments were administered 1 day after UC induction. The normal saline(2 mL) was instilled twice a day through the tube in the sham operation group and model group. 5-ASA was given via the tube in the topical 5-ASA group(7.5 g/L, twice per day, 100 mg/kg), and rats in the oral Etiasa group and oral 5-ASA group intragastrically received Etiasa(7.5 g/L, twice per day, 100 mg/kg) and 5-ASA(7.5 g/L, twice per day, 100 mg/kg), respectively. The body weight was recorded every day. After 7 days of treatment, blood samples were drawn from the heart to harvest the sera. Colonic tissues were separated and prepared for pathological and related molecular biological examinations. The concentrations of 5-ASA were detected at different time points in the colonic tissues, feces and sera in different groups by using the high pressure liquid chromatography(HPLC). The results showed that the symptoms of acute UC, including bloody diarrhea and weight loss, were significantly improved in topical 5-ASA-treated rats. The colonic mucosal damage, both macroscopical and histological, was significantly relieved and the myeloperoxidase activity was markedly decreased in rats topically treated with 5-ASA compared with those treated with oral 5-ASA or Etiasa. The mRNA and protein expression of IL-1β, IL-6, and TNF-α was down-regulated in the colonic tissue of rats topically treated with 5-ASA, significantly lower than those from rats treated with oral 5-ASA or Etiasa. The concentrations of 5-ASA in the colonic tissue were significantly higher in the topical 5-ASA group than in the oral 5-ASA and oral Etiasa groups. It was concluded that the topical administration of 5-ASA can effectively increase the concentration of 5-ASA in the colonic tissue, decrease the expression of proinflammatory cytokines, alleviate the colonic pathological damage and improve the symptoms of TNBS-induced acute UC in rats. 展开更多
关键词 ulcerative colitis 5-aminosalicylic acid 2 4 6-trinitrobenzene sulfonic acid
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选择性环氧合酶-2抑制剂PC407对TNBS诱导的大鼠溃疡性结肠炎的治疗作用 被引量:5
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作者 白卉 张邦乐 +4 位作者 李宇华 游宇 郭振军 孙阳 梅其炳 《世界华人消化杂志》 CAS 北大核心 2008年第12期1287-1293,共7页
目的:观察新型选择性环氧合酶-2抑制剂PC407对2,4,6-三硝基苯磺酸(2,4,6-trinitrobenzene sulfonic acid,TNBS)诱导的大鼠溃疡性结肠炎的疗效并探讨其机制.方法:应用TNBS/乙醇灌肠复制大鼠溃疡性结肠炎模型.实验设正常对照组、模型对照... 目的:观察新型选择性环氧合酶-2抑制剂PC407对2,4,6-三硝基苯磺酸(2,4,6-trinitrobenzene sulfonic acid,TNBS)诱导的大鼠溃疡性结肠炎的疗效并探讨其机制.方法:应用TNBS/乙醇灌肠复制大鼠溃疡性结肠炎模型.实验设正常对照组、模型对照组、塞来昔布阳性对照组(18mg/kg)和PC407治疗组(9,18mg/kg),ig给药,每天1次,共6d,观察稀便出现情况.实验第7天,麻醉大鼠,分离大鼠结肠、脾脏、胸腺,观察各组实验动物体质量变化及结肠组织病理学改变,选用稀便率、结肠指数、溃疡比、胸腺指数和脾脏指数作为衡量治疗效果的指标.采用免疫组织化学方法检测结肠黏膜环氧合酶-2(COX-2)和肿瘤坏死因子α(tumornecrosisfactor-alpha,TNF-α)的变化.结果:与模型组相比,18mg/kgPC407治疗可明显阻止结肠炎大鼠的体质量下降(258.9gvs223.6g,P<0.05),降低稀便发生率(30%vs80%,P<0.01),改善大鼠结肠组织损伤及病理学改变,包括降低结肠指数(5.03±1.26mg/gvs7.60±2.07mg/g,P<0.01)及溃疡比(24.69%±2.83%vs36.13%±9.64%,P<0.01);同时,PC407治疗可对抗结肠炎症引起的胸腺萎缩(1.96±0.48mg/gvs1.08±0.32mg/g,P<0.01)和脾脏肿大(2.85±0.33mg/gvs3.87±0.96mg/g,P<0.01),显著降低结肠炎大鼠结肠黏膜COX-2和TNF-α的阳性表达率(30.6%±7.0%vs67.4%±1.2%,19.5%±3.0%vs52%±4.7%,P<0.01).9mg/kgPC407也可以改善以上指数,只是作用没有18mg/kg明显.结论:PC407对TNBS/乙醇诱导的大鼠溃疡性结肠炎治疗作用良好,其机制可能通过下调COX-2及TNF-α的表达,从而缓解结肠炎症. 展开更多
关键词 选择性环氧合酶-2抑制剂 溃疡性结肠炎 2 4 6-三硝基苯磺酸 免疫组织化学 环氧合酶 肿瘤坏死因子-Α
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己酮可可碱对2,4,6-三硝基苯磺酸肠炎模型的影响 被引量:7
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作者 张炳勇 吕愈敏 +5 位作者 洪天配 李军 李付英 张玲 董秀云 王新娟 《中国新药杂志》 CAS CSCD 北大核心 2003年第6期429-432,共4页
目的 :观察己酮可可碱 (PTX)对 2 ,4 ,6 三硝基苯磺酸 (TNBS)肠炎模型影响。方法 :通过直肠给予雄性BALB/c小鼠TNBS诱导结肠炎 ,应用PTX对其进行治疗 ,6d后收集结肠标本评价结肠炎症程度 ;采用半定量RT PCR检测肠黏膜IL 18mRNA表达 ,... 目的 :观察己酮可可碱 (PTX)对 2 ,4 ,6 三硝基苯磺酸 (TNBS)肠炎模型影响。方法 :通过直肠给予雄性BALB/c小鼠TNBS诱导结肠炎 ,应用PTX对其进行治疗 ,6d后收集结肠标本评价结肠炎症程度 ;采用半定量RT PCR检测肠黏膜IL 18mRNA表达 ,采用免疫组织化学染色显示IL 18阳性细胞。结果 :直肠内给予BALB/c小鼠TNBS后可造成小鼠结肠炎性改变 ;PTX治疗可使小鼠疾病活动指数、结肠重量和炎症指数均显著下降 (P <0 .0 5 ) ,结肠IL 18mRNA和肠黏膜固有层表达IL 18细胞数显著下降 (P <0 .0 5 )。结论 :PTX治疗可使TNBS肠炎模型小鼠肠黏膜局部IL 18表达显著下降 ,肠炎得以减轻。 展开更多
关键词 白细胞介素18 2 4 6-三硝基苯磺酸(tnbs)肠炎 己酮可可碱
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美沙拉嗪缓释剂对2,4,6-三硝基苯磺酸诱导大鼠溃疡性结肠炎的治疗作用 被引量:8
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作者 李进 邓豫 +5 位作者 李兆明 曹小年 李小兰 陶德定 胡俊波 王晶 《医药导报》 CAS 2011年第7期839-842,共4页
目的研究美沙拉嗪缓释剂对2,4,6-三硝基苯磺酸(2,4,6-trinitro picrylsulfonic acid,TNBS)诱导的溃疡性结肠炎肿瘤坏死因子α(tumor necrosis factorα,TNF-α)、白细胞介素(interleukin,IL)-1β、IL-6表达的影响,探讨美沙拉嗪缓释剂的... 目的研究美沙拉嗪缓释剂对2,4,6-三硝基苯磺酸(2,4,6-trinitro picrylsulfonic acid,TNBS)诱导的溃疡性结肠炎肿瘤坏死因子α(tumor necrosis factorα,TNF-α)、白细胞介素(interleukin,IL)-1β、IL-6表达的影响,探讨美沙拉嗪缓释剂的抗炎机制。方法应用TNBS/乙醇建立大鼠溃疡性结肠炎模型,实验设正常对照组、模型组、药物治疗组(给予美沙拉嗪溶液100 mg.kg-1.d-1),阳性对照组(给予5-对氨基水杨酸100 mg.kg-1.d-1),每组10只,每天灌胃2次,给药时间从造模后第1天开始至实验结束,共7 d,观察大鼠疾病活动指数(disease index,DAI)、体质量变化及结肠病理学改变,生化法检查大鼠结肠组织髓过氧化物酶(myeloperoxidase,MPO)活性,逆转录聚合酶链反应(Real-time PCR)检测肠组织TNF-α、IL-1β、IL-6mRNA的表达水平。结果与正常对照组比较,模型组大鼠结肠组织MPO活性及TNF-α、IL-1β、IL-6mRNA表达量明显增多(P<0.05)。与模型组和阳性对照组比较,药物治疗组MPO活性及结肠组织TNF-α、IL-1β、IL-6mRNA的表达明显减少(P<0.05)。模型组和阳性对照组差异无统计学意义。结论美沙拉嗪缓释剂对大鼠实验性溃疡性结肠炎具有治疗作用,其机制与通过降低中性粒细胞的浸润、抑制促炎因子TNF-α、IL-1β、IL-6mRNA等的表达有关。 展开更多
关键词 美沙拉嗪缓释剂 结肠炎 溃疡性 2 4 6-三硝基苯磺酸 肿瘤坏死因子Α 白细胞介素
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2,4,6-三硝基苯磺酸诱导雏鸡溃疡性结肠炎模型的建立 被引量:2
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作者 于志强 周英 郑世民 《畜牧兽医学报》 CAS CSCD 北大核心 2015年第9期1686-1691,共6页
为探索动物溃疡性肠炎的发生发展机制及其对机体的影响,以10日龄SPF雏鸡为研究对象,以2,4,6-三硝基苯磺酸(TNBS)为诱导剂,分别根据体重应用50、100、150mg·kg-1的TNBS(50%乙醇稀释)通过灌肠途经建立TNBS诱导的雏鸡溃疡性结肠炎动... 为探索动物溃疡性肠炎的发生发展机制及其对机体的影响,以10日龄SPF雏鸡为研究对象,以2,4,6-三硝基苯磺酸(TNBS)为诱导剂,分别根据体重应用50、100、150mg·kg-1的TNBS(50%乙醇稀释)通过灌肠途经建立TNBS诱导的雏鸡溃疡性结肠炎动物模型,进而分析TNBS对雏鸡溃疡性结肠炎发生的剂量效应。并对TNBS所致的溃疡性结肠炎雏鸡的临诊症状、眼观和病理组织以及体重等变化进行较全面系统的观察或检测,结果发现,100mg·kg-1 TNBS为制备雏鸡溃疡性结肠炎动物模型的理想给药剂量,其能够得到理想的实验动物临诊症状和病理变化,同时对雏鸡的损伤在可控范围内,不会造成模型动物的大批死亡。本研究成功建立雏鸡溃疡性结肠炎病理模型,为进一步研究溃疡性结肠炎的发生发展奠定了基础。 展开更多
关键词 2 4 6-三硝基苯磺酸 雏鸡 溃疡性结肠炎
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己烯雌酚对2、4、6-三硝基苯磺酸/乙醇诱导的大鼠结肠炎的影响 被引量:3
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作者 金艳 刘莉 +4 位作者 王庆伟 王志鹏 李宇华 冯娟 梅其炳 《中国临床药理学与治疗学》 CAS CSCD 2006年第2期168-172,共5页
目的:观察己烯雌酚对2、4、6-三硝基苯磺酸(trinitrobenzene sulfonic,TNBS)/乙醇诱导的大鼠结肠炎的双向调节作用。方法:TNBS诱导大鼠结肠炎模型,肌肉注射己烯雌酚(50、100、150、200μg.kg-1),每天1次,共7 d。给药结束后,乙醚麻醉大鼠... 目的:观察己烯雌酚对2、4、6-三硝基苯磺酸(trinitrobenzene sulfonic,TNBS)/乙醇诱导的大鼠结肠炎的双向调节作用。方法:TNBS诱导大鼠结肠炎模型,肌肉注射己烯雌酚(50、100、150、200μg.kg-1),每天1次,共7 d。给药结束后,乙醚麻醉大鼠,打开腹腔,截取8 cm结肠,称重,画取溃疡面积,取病变组织以作HE染色,分离肠粘膜待测MPO活性;并取胸腺、脾脏称量。结果:50μg.kg-1己烯雌酚对结肠炎无明显治疗作用,反而引起肠道粘连和腹膜炎,加重炎症;100μg.kg-1的己烯雌酚对结肠炎具明显疗效;150和200μg.kg-1己烯雌酚能明显改善结肠炎各项指标,但大鼠全身状态差,死亡率增高。结论:适当剂量的己烯雌酚对结肠炎具有治疗作用,小剂量的己烯雌酚能够加重结肠炎的发生。 展开更多
关键词 己烯雌酚 结肠炎 细胞因子 246-三硝 基苯磺酸 自身免疫
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不同造模次数对2,4,6-三硝基苯磺酸/乙醇诱导重症溃疡性结肠炎模型大鼠的影响 被引量:16
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作者 刘佳丽 杨坤 +3 位作者 徐爱玲 刘一东 谷雪松 孙平良 《中国组织工程研究》 CAS 北大核心 2019年第27期4363-4368,共6页
背景:实验采取复合法2,4,6-三硝基苯磺酸(2,4,6-Trinitrobenzenesulfonic acid,TNBS)/乙醇建立溃疡性结肠炎大鼠模型,操作简单,持续时间长且组织学变化与人类溃疡性结肠炎相似,是目前常用的溃疡性结肠炎动物模型之一,但对不同剂量不同... 背景:实验采取复合法2,4,6-三硝基苯磺酸(2,4,6-Trinitrobenzenesulfonic acid,TNBS)/乙醇建立溃疡性结肠炎大鼠模型,操作简单,持续时间长且组织学变化与人类溃疡性结肠炎相似,是目前常用的溃疡性结肠炎动物模型之一,但对不同剂量不同造模次数仍存在较大差异。目的:采用相同剂量TNBS/乙醇不同次数诱导重症溃疡性结肠炎大鼠模型,探索重症溃疡性结肠炎适宜的造模次数。方法:选用SPF级SD大鼠80只,购自湖南斯莱克景达实验动物有限公司,实验方案经广西中医药大学第一附属医院动物实验伦理委员会批准[批准号为2013(KF)-E-003]。随机将大鼠分为正常对照组、TNBS+乙醇灌肠1次组、TNBS+乙醇灌肠2次组、TNBS+乙醇灌肠3次组。用药组分别使用灌胃针经大鼠直肠注入相同剂量的100 mg/kg TNBS+等体积乙醇1 d、连续2 d、连续3 d。分别于给药后的3,7 d各处死10只大鼠,观察大鼠生理状态、结肠形态、疾病活动指数及组织病理学改变情况。结果与结论:①造模7 d后大鼠体质量变化,随着造模次数的增加,大鼠体质量呈渐进性下降、症状呈渐进性加重趋势,DAI评分各组呈上升趋势;②TNBS+乙醇灌肠3次组体质量显著低于其他组(P<0.05);DAI评分和大体评分均显著高于其他组(P <0.05);③病理结果示,TNBS+乙醇灌肠3次组病变位于结肠黏膜肌层,杯状细胞丢失,隐窝形态不规则,排列紊乱,大部分可见溃疡面,较TNBS+乙醇灌肠1次组和TNBS+乙醇灌肠2次组更符合重症溃疡性结肠炎的病理表现;④结果说明,TNBS/乙醇造模中,100 mg/kg TNBS+乙醇灌肠3次连续灌肠更符合重症溃疡性结肠炎模型。 展开更多
关键词 重症溃疡性结肠炎 2 4 6-三硝基苯磺酸 大鼠 动物模型 造模次数 国家自然科学基金
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植物乳杆菌对2,4,6-三硝基苯磺酸诱导的小鼠结肠炎的治疗作用 被引量:3
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作者 叶胜青 赵志鸿 +1 位作者 夏阳 陈红旗 《世界华人消化杂志》 CAS 北大核心 2011年第8期794-799,共6页
目的:评估益生菌植物乳杆菌(LP)对三硝基苯磺酸(TNBS)诱导小鼠肠道炎症损伤的治疗作用,并探讨其可能的作用机制.方法:将成年♀Balb/c小鼠随机分成3组:正常对照组(Control组),TNBS灌肠诱导小鼠结肠炎组(TNBS组)和LP干预组(TNBS+LP组).TNB... 目的:评估益生菌植物乳杆菌(LP)对三硝基苯磺酸(TNBS)诱导小鼠肠道炎症损伤的治疗作用,并探讨其可能的作用机制.方法:将成年♀Balb/c小鼠随机分成3组:正常对照组(Control组),TNBS灌肠诱导小鼠结肠炎组(TNBS组)和LP干预组(TNBS+LP组).TNBS诱导肠炎模型建立后,给予TNBS+LP组小鼠灌胃LP3wk,其余两组灌胃空白对照PBS液.实验结束后对大鼠一般情况、结肠大体损伤及组织学损伤进行评估,并对各组小鼠结肠组织髓过氧化物酶(MPO)活性、LTB4含量及促炎细胞因子TNF-α和IFN-γ的表达进行测定.结果:与TNBS诱导的TNBS组相比,LP明显减轻了TNBS诱导的小鼠结肠炎症,表现为疾病活动指数下降(3.37±0.36vs0.97±0.47,P<0.05),结肠大体和组织学评分显著降低(1.11±0.61vs4.62±0.40;1.48±0.40vs5.39±1.12,均P<0.05),且LP显著降低了TNBS诱导的小鼠结肠黏膜内中性粒细胞浸润,这与MPO活性降低相一致(25.14U/g±5.22U/gvs90.3U/g±7.70U/g,P<0.05).此外,LP明显降低了TNBS诱导的小鼠结肠内具有化学趋化活性的LTB4含量(3.13ng/g±0.10ng/gvs8.43ng/g±0.49ng/g,P<0.05)和增加了促炎细胞因子TNF-α和IFN-γ的表达(205ng/g±68ng/gvs375ng/g±79ng/g;446ng/g±116ng/gvs603ng/g±109ng/g,均P<0.05).结论:口服植物乳杆菌能有效缓解TNBS诱导的小鼠结肠炎症状,其作用机制可能与其降低白细胞聚集及促炎细胞因子的表达有关. 展开更多
关键词 2 4 6-三硝基苯磺酸钠 植物乳杆菌 结肠炎 炎症性肠病 促炎细胞因子
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γ-氨基丁酸改善2,4,6-三硝基苯磺酸-乙醇诱导的结肠炎肠黏膜屏障损伤作用 被引量:5
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作者 蒋廷媛 岳源 李芳华 《医药导报》 CAS 北大核心 2018年第8期931-938,共8页
目的探讨γ-氨基丁酸(GABA)改善2,4,6-三硝基苯磺酸(TNBS)-乙醇诱导的结肠炎肠黏膜屏障损伤作用。方法 SD大鼠随机分为正常对照组,TNBS-乙醇溶液模型对照组,造模后GABA 200,100,50 mg·kg-1治疗组。造模后连续14 d,观察记录体质量... 目的探讨γ-氨基丁酸(GABA)改善2,4,6-三硝基苯磺酸(TNBS)-乙醇诱导的结肠炎肠黏膜屏障损伤作用。方法 SD大鼠随机分为正常对照组,TNBS-乙醇溶液模型对照组,造模后GABA 200,100,50 mg·kg-1治疗组。造模后连续14 d,观察记录体质量变化、疾病活动指数(DAI);造模第15天,每组取5只,进行伊文思蓝染色。大鼠取结肠,组织学损伤评分,同时量取结肠长度、称重。通过WB法观察实验性结肠炎各组大鼠肠黏膜屏障连接蛋白及LC3表达情况。结果 GABA增加Caco-2细胞单层模型细胞电阻,减少FD4的渗透,降低单层模型通透性。GABA改善实验性结肠炎引起的体质量下降,增加DAI,降低结肠指数。另外,GABA降低实验性结肠炎大鼠伊文思蓝渗透性及结肠病理变化,显著提高大鼠Occludin、Claudin-4、ZO-1蛋白表达。实验性结肠炎大鼠肠细胞出现过度自噬,GABA抑制过度自噬。结论GABA通过改善肠黏膜屏障损伤,缓解TNBS-乙醇溶液诱导的实验性结肠炎,故改善肠黏膜屏障损伤可能是治疗炎症性肠病(IBD)的新方法。 展开更多
关键词 Γ-氨基丁酸 2 4 6-三硝基苯磺酸 炎症性肠病 肠黏膜屏障
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2,4,6-三硝基苯磺酸与不同浓度乙醇诱导大鼠溃疡性结肠炎模型的建立及其稳定性评价 被引量:12
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作者 曾于恒 杨芳 何永恒 《中南药学》 CAS 2017年第12期1665-1669,共5页
目的建立2,4,6-三硝基苯磺酸(TNBS)-乙醇混合液诱导大鼠溃疡性结肠炎模型并判断不同浓度的乙醇对模型稳定性的影响。方法将80只雄性SD大鼠,随机分为空白组、模型Ⅰ组、模型Ⅱ组、模型Ⅲ组共4组,每组各20只,模型Ⅰ、Ⅱ、Ⅲ组大鼠分别给予... 目的建立2,4,6-三硝基苯磺酸(TNBS)-乙醇混合液诱导大鼠溃疡性结肠炎模型并判断不同浓度的乙醇对模型稳定性的影响。方法将80只雄性SD大鼠,随机分为空白组、模型Ⅰ组、模型Ⅱ组、模型Ⅲ组共4组,每组各20只,模型Ⅰ、Ⅱ、Ⅲ组大鼠分别给予TNBS(100 mg·kg^(-1))-无水乙醇0.25 mL、TNBS(100 mg·kg^(-1))-50%乙醇0.25 mL、TNBS(100 mg·kg^(-1))-25%乙醇0.25 mL混合液灌肠,空白组大鼠给予等量生理盐水灌肠。造模后每日观察大鼠精神状态及死亡情况,计算大鼠的疾病活动指数(DAI),并于2、7、14、21、28 d分批处死相同数量的大鼠,采集结肠组织,计算结肠黏膜损伤指数(CMDI),同时进行HE染色,计算组织学损伤指数(TDI)。结果除空白组外,各模型组造模后均有明显的溃疡性结肠炎临床症状和病理学改变(P<0.05);各模型组的死亡率、DAI、CMDI、TDI评分均在造模后7 d高于其他时间点,且差异有统计学意义(P<0.05);模型Ⅲ组无死亡,与模型Ⅰ组、模型Ⅱ组相比,DAI、CMDI、TDI评分差异有统计学意义(P<0.05)。结论模型Ⅰ、Ⅱ、Ⅲ组均能成功诱导溃疡性结肠炎模型,以模型Ⅲ组死亡率较低、模型稳定性较好。 展开更多
关键词 溃疡性结肠炎 大鼠 模型 2 4 6-三硝基苯磺酸 疾病活动指数 结肠黏膜损伤指数 组织学损伤指数
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芝麻素对2,4,6-三硝基苯磺酸诱导的大鼠溃疡性结肠炎的影响 被引量:4
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作者 鲁磊 王绪新 《中南药学》 CAS 2013年第11期815-817,共3页
目的研究芝麻素对2,4,6-三硝基苯磺酸(TNBS)诱导的大鼠溃疡性结肠炎(UC)的保护作用。方法 Wistar大鼠50只,随机分为空白对照组,模型组和芝麻素低、中、高剂量5组,每组10只。用TNBS/乙醇灌肠法复制大鼠UC模型,芝麻素组分别给与不同剂量... 目的研究芝麻素对2,4,6-三硝基苯磺酸(TNBS)诱导的大鼠溃疡性结肠炎(UC)的保护作用。方法 Wistar大鼠50只,随机分为空白对照组,模型组和芝麻素低、中、高剂量5组,每组10只。用TNBS/乙醇灌肠法复制大鼠UC模型,芝麻素组分别给与不同剂量芝麻素进行灌胃治疗,10 d后处死全部大鼠,收集血液和结肠标本,ELISA法检测血清中IL-6、IL-10和TNF-α含量以及生化法检测结肠组织中髓过氧化物酶(MPO)、超氧化物歧化酶(SOD)活力以及一氧化氮(NO)、还原性谷胱甘肽(GSH)、丙二醛(MDA)含量。结果与模型组比较,芝麻素3个剂量组以及空白对照组血清TNF-α、IL-6含量显著降低,IL-10含量显著升高,差异有统计学意义(P<0.01或P<0.05)。与模型组相比,芝麻素3个剂量组以及空白对照组MPO活力及NO和MDA含量均降低,SOD活力与GSH含量升高,差异有统计学意义(P<0.01)。结论芝麻素可通过提高结肠炎大鼠结肠组织抗氧化能力,调节结肠炎大鼠血清炎性细胞因子的平衡,抑制NO生成,发挥治疗作用。 展开更多
关键词 芝麻素 2 4 6-三硝基苯磺酸 溃疡性结肠炎
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2,4,6-三硝基苯磺酸诱导溃疡性结肠炎大鼠模型的建立及评价 被引量:20
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作者 张冰冰 齐越 +3 位作者 贾冬 韦丹 康凯 明彩荣 《中华中医药学刊》 CAS 北大核心 2015年第8期1834-1836,I0002,共4页
目的建立大鼠2,4,6-三硝基苯磺酸(TBNS)溃疡性结肠炎(ulcerative colitis,UC)模型。方法:大鼠经结肠注入不同剂量的2,4,6-三硝基苯磺酸,分别于给药后1、3及7 d处死大鼠取出结肠,肉眼观察后进行组织学切片然后镜下观察。结果:各组大鼠体... 目的建立大鼠2,4,6-三硝基苯磺酸(TBNS)溃疡性结肠炎(ulcerative colitis,UC)模型。方法:大鼠经结肠注入不同剂量的2,4,6-三硝基苯磺酸,分别于给药后1、3及7 d处死大鼠取出结肠,肉眼观察后进行组织学切片然后镜下观察。结果:各组大鼠体质量于造模3 d后开始下降,50 mg·kg-1组体质量于7 d后开始出现回升,100 mg·kg-1组和150 mg·kg-1组体质量则没有恢复;造模时间不是影响UC(溃疡性结肠炎)损伤程度的主要因素;病理切片结果表明,50 mg·kg-1组可见炎性细胞浸润,未出现肠腺肿胀及黏膜脱落现象,符合UC(溃疡性结肠炎)的病理特征。结论:TNBS造模7 d内,UC(溃疡性结肠炎)的造模成功与否与给药天数无关,而与剂量密切关联,以50 mg·kg-1的大鼠给药剂量最为合适。 展开更多
关键词 溃疡性结肠炎 大鼠 模型 三硝基苯磺酸 HE染色 炎症性肠病
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Therapeutic and Immunoregulatory Effect of GATA-Binding Protein-3/T-Box Expressed in T-Cells Ratio of Astragalus Polysaccharides on 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Colitis in Rats 被引量:11
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作者 高永健 朱峰 +1 位作者 钱家鸣 戴佳原 《Chinese Journal of Integrative Medicine》 SCIE CAS CSCD 2016年第12期918-924,共7页
Objective: To analyze the immunological characteristics of 2,4,6-trinitrobenzene sulfonic acid(TNBS)-induced colitis model and examine the therapeutic effects and mechanisms of Astragalus polysaccharides(APS) tre... Objective: To analyze the immunological characteristics of 2,4,6-trinitrobenzene sulfonic acid(TNBS)-induced colitis model and examine the therapeutic effects and mechanisms of Astragalus polysaccharides(APS) treatment. Methods: Thirty-two male specific pathogen free Spragne-Dawley rats were randomly equally assigned to four groups: control, TNBS, APS and prednisone groups. Experimental colitis was induced by enema administration of TNBS. Then rats were treated with APS(0.5 g·kg^(-1)·day^(-1), once daily) or prednisone(1.0 mg·kg^(-1)·day^(-1), once daily) by gavage for 14 days. Macroscopic lesion and histological damage were determined, and activity of myeloperoxidase(MPO) was measured in the colonic tissues. Expressions of T-box expressed in T-cells(T-bet) and GATA-binding protein-3(GATA-3) were determined by immunohistochemistry analysis and western blot. Results: Both macroscopic lesion and histological colonic damage induced by TNBS were reduced by APS and prednisone treatment. These were accompanied by significant attenuation of MPO activity(P=0.03). TNBS intervention enhanced the expression of both GATA-3 and T-bet, but the expression of T-bet was significantly enhanced than that of GATA-3, resulting in significant reduction of GATA-3/T-bet ratio(P=0.025). APS administration enhanced the expression of T-bet(P=0.04) and GATA-3(P=0.019) in comparison to TNBS group, and resulting in an up-regulated GATA-3/T-bet ratio. Prednisone treatment inhibited both expressions; however it also resulted in up-regulation of the GATA-3/T-bet ratio. Conclusions: These results demonstrated that APS exerted a beneficial immune regulatory effect on experimental colitis. It promoted the expression of T helper cell 1(Th1) and T helper cell 2(Th2) specific transcription factors but ultimately favor a shift toward Th2 phenotype, suggesting that APS possessed therapeutic potential in experimental colitis. 展开更多
关键词 Astragalus polysaccharides 2 4 6-trinitrobenzene sulfonic acid-induced colitis rats T-bet GATA-3 Chinese medicine
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基于CD40/CD40L探讨重楼总皂苷对TNBS诱导的大鼠急性实验性结肠炎作用机制 被引量:2
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作者 刘可心 王卯 +4 位作者 吴星星 吴琪 王耀辉 刘丽波 吴静 《山西中医》 2023年第4期51-56,共6页
目的:探讨重楼总皂苷(rhizomaparidis total saponins,RPTS)对三硝基苯磺酸(2,4,6-trinitrobenzene sulfonic acid,TNBS)诱导的急性实验性结肠炎大鼠炎症与凝血的影响及其作用机制。方法:将50只雄性SPF级SD大鼠,随机分为空白组7只,模型... 目的:探讨重楼总皂苷(rhizomaparidis total saponins,RPTS)对三硝基苯磺酸(2,4,6-trinitrobenzene sulfonic acid,TNBS)诱导的急性实验性结肠炎大鼠炎症与凝血的影响及其作用机制。方法:将50只雄性SPF级SD大鼠,随机分为空白组7只,模型组13只,以及美沙拉嗪组、RPTS低剂量组及RPTS高剂量组,每组各10只。通过TNBS建立大鼠急性实验性结肠炎模型,共14天。实验评估终点生存率、DAI评分、CMDI评分、TDI评分等指标,探究RPTS对大鼠急性实验性结肠炎的量效关系。检测全血细胞及凝血等相关指标;采用ELISA方法检测血浆及肝脏组织中CD40/CD40L指标,采用RT-PCR方法检测结肠组织中IL-1β及TNF-α的m RNA水平。结果:模型组终点生存率76.9%,RPTS低剂量组生存率为100%;RPTS低剂量组DAI、CMDI及TDI评分均较模型组显著降低(P﹤0.05);在肝脏组织中的CD40/CD40L表达水平与模型组比较,美沙拉嗪组及RPTS低剂量组均显著增加(P﹤0.0001);同时,在结肠组织的IL-1βm RNA检测中,与模型组比较,RPTS低剂量组IL-1β mRNA降低(P﹤0.05)。结论:RPTS改善了TNBS诱导急性实验性结肠炎大鼠的症状,具有良好的治疗作用,提高了模型鼠的终点生存率;RPTS低剂量组治疗效果更佳,可能通过激活CD40/CD40L共刺激因子,调控实验性结肠炎大鼠的免疫机制,以缓解疾病的炎症反应。 展开更多
关键词 实验性结肠炎 重楼总皂苷 2 4 6-三硝基苯磺酸 CD40/CD40L 实验研究
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Hyaluronic acid as a rescue therapy for trinitrobenzene sulfonica cid-induced colitis through Cox-2 and PGE_2 in a Toll-like receptor 4-dependent way
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作者 Mahesh MAHASETH 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2011年第9期712-719,共8页
We hypothesized whether systemic administration of high-molecular-weight hyaluronic acid(HMW HA) could rescue trinitrobenzene sulfonic acid(TNBS)-induced colitis through Toll-like receptor 4(TLR4) signal.C3H/HeN mice ... We hypothesized whether systemic administration of high-molecular-weight hyaluronic acid(HMW HA) could rescue trinitrobenzene sulfonic acid(TNBS)-induced colitis through Toll-like receptor 4(TLR4) signal.C3H/HeN mice and C3H/HeJ mice were used.Mice were divided into four groups:control,50% ethanol treatment group,TNBS treatment group,and TNBS plus HA treatment group.The weight changes,clinical scores,macroscopic scores,and histological scores were recorded.Cyclooxygenase 2(Cox-2) and prostaglandin E 2(PGE 2) expressions were measured both in colons and peritoneal macrophages from these mice.HA was a rescue therapy for the colitis induced by TNBS only in C3H/HeN mice.The clinical score,macroscopic score,and histological score were much lower in C3H/HeN mice receiving TNBS plus HA treatment.Cox-2 and PGE 2 expressions only increased in C3H/HeN mice.These Cox-2 expressing cells were macrophages.HA can also promote the production of Cox-2 and PGE 2 in peritoneal macrophages from C3H/HeN mice.Our data demonstrated that HMW HA can rescue TNBS-induced colitis through inducing Cox-2 and PGE 2 expressions in a TLR4-dependent way.Macrophages may be the effector cells of HMW HA. 展开更多
关键词 trinitrobenzene 酸性硫酸基的酸(tnbs ) 大肠炎 治疗 玻尿的酸 像使用费的受体
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Recombinant adeno-associated virus carrying thymosin β4 suppresses experimental colitis in mice 被引量:5
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作者 Xiao-Yan Zheng Yi-Fei Lv +4 位作者 Shuang Li Qian Li Qian-Nan Zhang Xue-Ting Zhang Zhi-Ming Hao 《World Journal of Gastroenterology》 SCIE CAS 2017年第2期242-255,共14页
AIM To investigate the protective effect of a recombinant adeno-associated virus carrying thymosin β4(AAV-Tβ4) on murine colitis via intracolonic administration.METHODS AAV-Tβ4 was prepared and intracolonically use... AIM To investigate the protective effect of a recombinant adeno-associated virus carrying thymosin β4(AAV-Tβ4) on murine colitis via intracolonic administration.METHODS AAV-Tβ4 was prepared and intracolonically used to mediate the secretory expression of Tβ4 in mouse colons. Dextran sulfate sodium(DSS) was applied to induce the murine ulcerative colitis, and 2,4,6-trinitrobenzene sulfonic acid(TNBS) was used to establish a mouse colitis model resembling Crohn's disease. The disease severity and colon injuries were observed and graded to reveal the effects of AAV-Tβ4 on colitis. The activities of myeloperoxidase(MPO) and superoxide dismutase(SOD) and the content of malondialdehyde(MDA) were determined using biochemical assays. Colonic levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β and IL-10 were measured using ELISA, and mucosal epithelial cell apoptosis andproliferation were detected by TUNEL assay and immunochemistry, respectively.RESULTS Recombinant AAVs efficiently delivered Lac Z and Tβ4 into the colonic tissues of the mice, and AAV-Tβ4 led to a strong expression of Tβ4 in mouse colons. In both the DSS and TNBS colitis models, AAV-Tβ4-treated mice displayed distinctly attenuated colon injuries and reduced apoptosis rate of colonic mucosal epithelia. AAV-Tβ4 significantly reduced inflammatory cell infiltrations and relieved oxidative stress in the inflamed colons of the mice, as evidenced by decreases in MPO activity and MDA content and increases in SOD activity. AAV-Tβ4 also modulated colonic TNF-α, IL-1β and IL-10 levels and suppressed the compensatory proliferation of colonic epithelial cells in DSS- and TNBS-treated mice.CONCLUSION Tβ4 exerts a protective effect on murine colitis, indicating that AAV-Tβ4 could potentially be developed into a promising agent for the therapy of inflammatory bowel diseases. 展开更多
关键词 Thymosin ;2 4 老鼠 大肠炎 葡聚糖硫酸盐钠 2 4 6-trinitrobenzene 酸性硫酸基的酸
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Colon-specific prodrugs of 4-aminosalicylic acid for inflammatory bowel disease 被引量:4
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作者 Suneela S Dhaneshwar 《World Journal of Gastroenterology》 SCIE CAS 2014年第13期3564-3571,共8页
Despite the advent of biological products,such as antitumor necrosis factor-αmonoclonal antibodies(infliximab and adalimumab),for treatment of moderate to severe cases of inflammatory bowel disease(IBD),most patients... Despite the advent of biological products,such as antitumor necrosis factor-αmonoclonal antibodies(infliximab and adalimumab),for treatment of moderate to severe cases of inflammatory bowel disease(IBD),most patients depend upon aminosalicylates as the conventional treatment option.In recent years,the increased knowledge of complex pathophysiological processes underlying IBD has resulted in development of a number of newer pharmaceutical agents like low-molecular-weight heparin,omega-3 fatty acids,probiotics and innovative formulations such as high-dose,oncedaily multi-matrix mesalamine,which are designed to minimize the inflammatory process through inhibition of different targets.Optimization of delivery of existing drugs to the colon using the prodrug approach is another attractive alternative that has been utilized and commercialized for 5-aminosalicylic acid(ASA)in the form of sulfasalazine,balsalazide,olsalazine and ipsalazine,but rarely for its positional isomer 4-ASA-a wellestablished antitubercular drug that is twice as potent as 5-ASA against IBD,and more specifically,ulcerativecolitis.The present review focuses on the complete profile of 4-ASA and its advantages over 5-ASA and colon-targeting prodrugs reported so far for the management of IBD.The review also emphasizes the need for reappraisal of this promising but unexplored entity as a potential treatment option for IBD. 展开更多
关键词 4-Aminosalicylic acid 5-Aminosalicylic acid Sulfas
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溃疡性结肠炎大鼠结肠黏膜SOCS2、SOCS3的表达及意义 被引量:6
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作者 周婷婷 仝巧云 袁晋华 《华中科技大学学报(医学版)》 CAS CSCD 北大核心 2015年第3期285-288,297,共5页
目的研究溃疡性结肠炎大鼠结肠黏膜细胞因子信号转导抑制子SOCS2、SOCS3的表达,探讨其与溃疡性结肠炎的关系。方法将30只雄性SD大鼠随机均分为正常对照组、结肠炎模型组和柳氮磺胺吡啶(SASP)组,采用三硝基苯磺酸(TNBS)诱导制备溃疡性结... 目的研究溃疡性结肠炎大鼠结肠黏膜细胞因子信号转导抑制子SOCS2、SOCS3的表达,探讨其与溃疡性结肠炎的关系。方法将30只雄性SD大鼠随机均分为正常对照组、结肠炎模型组和柳氮磺胺吡啶(SASP)组,采用三硝基苯磺酸(TNBS)诱导制备溃疡性结肠炎大鼠模型。观察大鼠一般情况并评价疾病活动指数(DAI),造模7d后处死大鼠,评价其组织学损伤指数(CMDI)及肠黏膜损伤指数(TDI);采用免疫比浊法检测血清C-反应蛋白(CRP)浓度;采用RT-PCR及Western blot检测结肠组织IL-6mRNA、SOCS2、SOCS3mRNA及蛋白的表达。结果结肠炎模型组DAI、CMDI、TDI评分及CRP水平显著高于正常对照组,SASP组显著低于模型组,差异均有统计学意义(均P<0.01);结肠炎模型组IL-6 mRNA、SOCS2和SOCS3 mRNA及蛋白表达高于正常对照组(均P<0.05),SASP组IL-6 mRNA、SOCS2、SOCS3mRNA及蛋白表达低于模型组(均P<0.05)。结论溃疡性结肠炎中SOCS2、SOCS3的表达与疾病严重程度相关,随着炎症程度的加重,SOCS2、SOCS3的表达水平上调。 展开更多
关键词 溃疡性结肠炎 三硝基苯磺酸 柳氮磺胺吡啶 细胞因子信号转导抑制子
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Effects of Changtai granules, a traditional compound Chinese medicine, on chronic trinitrobenzene sulfonic acid-induced colitis in rats 被引量:5
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作者 Yong-Bing Cao,Jun-Dong Zhang,Lan Yan,De-Jun Wang,Xin-Ming Jia,Ping-Hui Gao,Ming-He Cheng,Zheng Xu,Yan Wang,Yuan-Ying Jiang,Department of Pharmacology,School of Pharmacy,Second Military Medical University,Shanghai 200433,China Ya-Ying Diao,Department of Pharmacy,Changhai Hospital,Second Military Medical University,Shanghai 200433,China 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第23期3539-3543,共5页
AIM: To study the effects of Changtai granules (CTG), a traditional compound Chinese medicine, on chronic trinitrobenzene sulfonic acid-induced colitis in rats. METHODS: Healthy adult Sprague-Dawley (SD) rats of both ... AIM: To study the effects of Changtai granules (CTG), a traditional compound Chinese medicine, on chronic trinitrobenzene sulfonic acid-induced colitis in rats. METHODS: Healthy adult Sprague-Dawley (SD) rats of both sexes, weighing 250-300 g, were employed in the present study. The rat colitis models were induced by 2, 4,6-trinitrobenzene sulfonic acid (TNBS) enemas at a concentration of 100 mg/kg in 50% ethanol. The experimental animals were randomly divided into dexamethasone (DX) treatment, CTG treatment, and model control groups, which were intracolicly treated daily with DX (0.2 mg/kg), CTG at doses of 2.9, 5.7 and 11.4 g crude drug/kg, and the equal amount of saline respectively from 6 h following induction of the colitis in rats inflicted with TNBS to the end of study. A normal control group of rats treated without TNBS but saline enema was also included in the study. After 3 wk of treatment, the animals were assessed for colonal inflammatory and ulcerative responses with respect to mortality, frequency of diarrhea, histology and myeloperoxidase activity (MPO).RESULTS: The therapeutic effect of CTG on ulcerative colitis (UC) was better than DX. CTG effectively inhibited the activity of granulocytes, macrophages and monocytes in a dosedependent manner. Also it reduced MPO and formation of inflammation in colonic mucosal tissue. Furthermore, administration of CTG significantly prevented body mass loss and death, and decreased frequency of diarrhea in UC rats, when compared with the model control group rats.CONCLUSION: CTG would prove to be an ideal drug for chronic UC, and is warranted to be studied further. 展开更多
关键词 中药制剂 慢性肠炎 小鼠 动物实验 磺酸三硝基苯
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Influence of Shenqing Recipe on Morphology and Quantity of Colonic Interstitial Cells of Cajal in Trinitrobenzene Sulfonic Acid Induced Rat Colitis 被引量:3
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作者 Yan-cheng Dai Zhi-peng Tang +2 位作者 Zhen-nan Wang Ya-li Zhang Xin-ying He 《Chinese Medical Sciences Journal》 CAS CSCD 2011年第1期43-48,共6页
Objective To observe the influence of Shenqing Recipe (SQR),a kind of Traditional Chinese Medicine,on the morphology and quantity of colonic interstitial cells of Cajal (ICC) in trinitrobenzene sulfonic acid (TNBS)-in... Objective To observe the influence of Shenqing Recipe (SQR),a kind of Traditional Chinese Medicine,on the morphology and quantity of colonic interstitial cells of Cajal (ICC) in trinitrobenzene sulfonic acid (TNBS)-induced rat colitis,and to investigate the possible mechanism of SQR in regulating intestinal dynamics.Methods Sixty rats were randomly divided into normal control,model Ⅰ,model Ⅱ,mesalazine,and high-dose,and low-dose SQR groups with 10 rats in each group.TNBS (10 mg) dissolved in 50% ethanol was instilled into the lumen of the rat colon of the latter five groups to induce colitis.On the 4th day after administration of TNBS,each treatment group was administered one of the following formulations by enteroclysis gavage once a day for 7 days:600 mg·kg-1·d-1 mesalazine,2.4 g·kg-1·d-1 SQR,and 1.2 g·kg-1·d-1 SQR.Model Ⅱ rats received normal saline solution.After 7 days colonic samples were collected.While the colonic samples of model Ⅰ group were collected on the 3rd day after TNBS administered.Ultrastructure of ICC in the damaged colonic tissues was observed with transmission electron microscope.Expression of c-kit protein in colonic tissue was determined by immunohistochemical staining and Western blot.Results The ultrastructure of colonic ICC in the rat model of TNBS-induced colitis showed a severe injury,and administration of SQR or mesalazine reduced the severity of injury.Similarly,the expression of c-kit protein of TNBS-induced colitis rat model was significantly decreased compared with the normal control group (P<0.05).Treatment with SQR or mesalazine significantly increased the expression of c-kit protein compared with the administration of control formulations (P<0.05),especially the high-dose SQR group.Conclusion SQR could alleviate and repair the injured ICC,and improve its quantity,which might be involved in regulating intestinal motility. 展开更多
关键词 大鼠模型 硝基苯磺酸 结肠炎 间质细胞 诱导 和数 形态 免疫组织化学染色
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