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白芍总苷对葡聚糖硫酸钠诱导的IBD模型小鼠炎症因子水平的影响作者：葛冰景曹红燕戴彦成阙任烨傅志泉来源：《湖南中医药大学学报》2020年第08期〔摘要〕目的探討白芍总苷对葡聚糖硫酸钠（dextran sulfate sodium， DSS）诱导的小鼠炎症性肠病（inflammatory bowel disease， IBD）模型的作用及相关机制研究。
方法将50只SPF级C57BL/6小鼠随机分成正常组（N组）、模型组（M组）、柳氮磺吡啶组（L组）、低剂量白芍总苷组（BL组）、高剂量白芍总苷组（BH组），每组10只。
M组及治疗组小鼠自由饮用30 g/L DSS，同时予以相应药物灌胃1次;N组自由饮水、进食，连续7 d后处死。
期间每天记录小鼠体质量及粪便情况，进行结肠炎疾病活动指数（disease activity index， DAI）评分，利用结肠组织HE染色进行组织病理学评价，利用ELISA法检测血清中IL-8、IL-10、IL-23、IL-36、CCL20、CCR6的表达。
结果与M组比较，用药组DAI评分均显著降低（P<0.05或P<0.01），各用药组之间差异无统计学意义（P>0.05）;与M组比较，用药组均可下调IL-8、IL-23、IL-36、CCL20和CCR6的表达，上调IL-10的表达，并以L组、BH组最为显著（P<0.05或P<0.01）;病理组织学结果显示，L组、BH组结肠组织的炎症反应得到了显著改善。
结论白芍总苷可以有效调节炎症因子表达，减少结肠组织的炎症损伤，并改善小鼠的腹泻及便血症状。
〔关键词〕白芍总苷;炎症性肠病;葡聚糖硫酸钠;炎症因子;疾病活动指数〔中图分类号〕R285.5 〔文献标志码〕A 〔文章编号〕doi：10.3969/j.issn.1674-070X.2020.08.010〔Abstract〕 Objective To explore the effect and the underlying mechanism of total glucosides of paeony on inflammatory factors in dextran sulfate sodium （DSS） induced-mice model of inflammatory bowel disease （IBD）. Methods A total of 50 SPF-class C57BL/6 mice were randomly divided into a normal group （N group）， a model group （M group）， a sulfasalazine group （L group）， a low-dose of total glucosides of paeony group （BL group） and high-dose of total glucosides of paeony group （BH group）， with 10 mice in each group. The mice in M group and treatment groups were free to drink 30 g/L DSS， and were given the corresponding medicine by gavage once， while the mice in the N group were free to drink water and eat. All the mice were executed 7 days later. During this period， the status of weight and feces of the mice were recorded，and colitis disease activity index （DAI） score were assessed. In addition， HE staining of colon tissue were performed to evaluate the histopathological injury， and the expression of serum IL-8，IL-10， IL-23， IL-36， CCL20 and CCR6 were determined by using ELISA. Results Compared with the M group， DAI scores of mice in the treatment group were significantly decreased （P<0.05 or P<0.01）， and the differences in each treatment group was not statistically significant（P>0.05）. Compared with the M group， the expression of IL-8， IL-23， IL-36， CCl20， and CCR6 were decreased in the treatment group， while the expression of IL-10 was increased， in which the L group and the BH group were most significant （P<0.05 or P<0.01）. The histopathological results showed that the inflammatory response of colon tissue in the L group and the BH group was significantly improved. Conclusion Total glucosides of paeony could effectively regulate the expression of inflammatory factors， reduce the inflammatory injury of colon tissues，and improve the diarrhea and hematochezia symptoms in mice.〔Keywords〕 total glucosides of paeony; inflammatory bowel disease; dextran sulfate sodium; inflammatory factor; disease activity index炎症性肠病（inflammatory bowel disease， IBD）是一组以腹痛、腹泻、黏液脓血便为主要表现的慢性非特异性肠道炎症性疾病，包括克罗恩病（Crohn's disease， CD）和溃疡性结肠炎（ulcerative colitis， UC）。
葡聚糖硫酸钠诱导C57BL／6J小鼠急性结肠炎模型的建立与评价徐丽红;肖芳;兰小琴;何嘉怡;丁强;田德安;郑勇【摘要】Objective The expression and impaired function of ion channels might be one of the pathophysiological mecha -nisms responsible for diarrhea in inflammatory bowel disease ( IBD) .Proper animal model is the key to explore detailed pathophysiolog-ical process.The purpose of this study was to build a rat model of acute colitis induced by dextran sodium sulfate (DSS) in C57BL/6 mice and evaluate diarrhea-associated clinical , histological , pathological parameters and expressions of ion channel protein . Methods C57BL/6J mice of model group were treated with4%DSS solution for 7 days to induce acute colitis.Mice body weight, stool moisture, stool consistency and the degree of hematochezia were recorded .The histopathological changes of mice colon specimens were observed visually and microcosmically, and the ion channel SLC26A3 protein was detected by Western Blot . Results All experimental mice survived.In the experiment, compared with control group , bloody diarrhea and weight lose occurred in model group , along with increased stool moisture ([73.30 ±8.31]% after experiment vs [44.32 ±6.42]% before experiment, P=0.004), and rapidly in-creased disease activity index (DAI) of acute colitis ([3.50 ±0.87] after experiment vs [1.0 ±0.00] before experiment, P=0.000).At the end of this experiment , compared with control group , the model group resulted in higher colonic damage scoreand pathological inflammation score (P=0.00, P=0.002), significantly shortened co-lon (P=0.00) and decreased expression of SLC26A3. Conclusion The intestinal mucosal injury and phenotypic features of4%DSS-induced acute colitis are very similar to those of human ulcerative colitis .Impaired expression of intestinal ion transporter SLC26 A3 coexists with diarrhea in model group mice , and this model can support the research on mechanism of functional changes of ion channels in inflammatory diarrhea .%目的：离子通道的表达和功能受损可能是引起炎症性肠病相关性腹泻的病理生理机制之一，合适的动物模型是探讨其中详细病理生理过程的关键。
网络出版时间：２０２１－４－２３１１：０１：００ 网络出版地址：ｈｔｔｐｓ：／／ｋｎｓ．ｃｎｋｉ．ｎｅｔ／ｋｃｍｓ／ｄｅｔａｉｌ／３４．１０８６．ｒ．２０２１０４２２．１４１３．０５０．ｈｔｍｌ葡聚糖硫酸钠自由饮用与灌胃诱导小鼠溃疡性结肠炎模型的比较茶亚飞，郭雪艳，李宝晶，李艳平，王 亭，毛晓健（云南中医药大学中药学院，云南昆明 ６５０５００）收稿日期：２０２０－１２－１６，修回日期：２０２１－０３－１５基金项目：国家自然科学基金资助项目（Ｎｏ８１７６０７４５，８１９６０７５０，８１９６０７７７）；云南省科技厅－云南中医学院应用基础研究联合专项项目［Ｎｏ２０１８ＦＦ００１（ ０１２），２０１８ＦＦ００１（ ０２４），２０１９ＦＦ００２（ ００５）］作者简介：茶亚飞（１９９５－），女，硕士生，研究方向：临床中药学，Ｅ ｍａｉｌ：２７３３２４３３１５＠ｑｑ．ｃｏｍ；王 亭（１９８５－），女，博士，副教授，硕士生导师，研究方向：中药、民族药抗炎免疫药理学，通讯作者，Ｅ ｍａｉｌ：ｗａｎ ｇｔ６６２＠ｈｏｔｍａｉｌ．ｃｏｍ；毛晓健（１９６７－），女，硕士，教授，硕士生导师，研究方向：临床中药学，中药药理学，通讯作者，Ｅ ｍａｉｌ：１２２４３４６２０４＠ｑｑ．ｃｏｍｄｏｉ：１０．３９６９／ｊ．ｉｓｓｎ．１００１－１９７８．２０２１．０５．０２５文献标志码：Ａ文章编号：１００１－１９７８（２０２１）０５－０７３５－０６中国图书分类号：Ｒ ３３２；Ｒ３６３ ３３２；Ｒ４５２；Ｒ５７４．６２；Ｒ９１６．４摘要：目的 比较不同浓度葡聚糖硫酸钠（ｄｅｘｔｒａｎｓｕｌｆａｔｅｓｏ ｄｉｕｍ，ＤＳＳ）在自由饮用和灌胃两种方式下诱导小鼠急性溃疡性结肠炎（ｕｌｃｅｒａｔｉｖｅｃｏｌｉｔｉｓ，ＵＣ）成模情况和模型相关指标变异系数，优选ＵＣ造模方法。
方法 小鼠随机分为正常组、３％ＤＳＳ溶液自由饮用组、４％ＤＳＳ溶液自由饮用组、３０％ＤＳＳ溶液灌胃组、４０％ＤＳＳ溶液灌胃组。
葡聚糖硫酸钠诱导的小鼠肠炎模型中炎性因子的变化徐永芳;郑小翠;王海燕;葛彦;居颂光;居颂文【期刊名称】《中国血液流变学杂志》【年(卷),期】2017(27)1【摘要】目的通过建立葡聚糖硫酸钠(DSS)诱导的小鼠肠炎模型,观察其炎性因子变化规律.方法选用C57BL/6雄性小鼠,随机分为DSS组与对照组,DSS组给予3%的DSS溶液自由饮用7d,对照组自由饮水.每天观察小鼠体重、便血、腹泻情况并进行DAI评分;于7d时处死小鼠,观察小鼠肠道形态学的变化;通过组织病理学技术分析肠绒毛长度、肠隐窝数量的变化;通过流式细胞微球芯片捕获技术检测小鼠血清中炎性细胞因子水平的变化.结果与对照组比较,DSS组小鼠出现明显的体重下降、便血、腹泻等症状,活动度及精神状态变差,DAI评分升高;小鼠肠道充血严重、大肠明显缩短;组织病理切片显示小鼠结肠隐窝结构破坏、减少、绒毛断裂、可见大量的炎性细胞浸润;小鼠血清中促炎性细胞因子IL-6、TNF-α上升,抗炎性细胞因子IL-10明显下降.结论抗炎性因子与促炎性因子失衡可能是炎性肠病的重要机制.%Objective To observe the changes of the pathological damage and inflammatory cytokine production in the DSS-induced colitismouse model. Methods The male C57BL/6 mice were fed 3％ (wt/vol) DSS dissolved in distilled water from day 0 to 7 to induce colitis. Animal body weight change, occult or gross rectal bleeding, and stool consistency were monitored for each mouse. The resultant inflammatory bowl disease (IBD) DAI represents the average of the scores of the colitis symptoms. Mice were sacrificed at day 7 after administration of DSS and the changes ofintestinal morphology were observed. The pathological changes such as length of villi, number of crypt were analyzed by histopathological technique. The changes of inflammatory cytokines in the serum of mice were analyzed by Cytometric Bead Array. Results DSS-treated mice had obvious weight loss, diarrhea, and blood in the stool. The DAI scorewas also significantly increased. The colon length were shorter. Distortion of crypt architecture, inflammatory cell infiltration ofinflammatory cell, the number of LGR5+ intestinal stem cells decreased. Levels of pro-inflammatory cytokines in serum such as IL-6, TNF-αwere increased. Levels of anti- inflammatory cytokine IL-10 was declined obviously. Conclusion DSS-induced colitis mouse model was successfully established, confirming the imbalances between anti-inflammatory cytokines and pro-inflammatory cytokines and the absence of LGR5+ stem cells in the crypt are important mechanisms of IBD.【总页数】5页(P12-16)【作者】徐永芳;郑小翠;王海燕;葛彦;居颂光;居颂文【作者单位】苏州大学医学部基础医学与生物科学学院免疫学系,江苏苏州215123;苏州大学医学部基础医学与生物科学学院免疫学系,江苏苏州 215123;苏州大学医学部基础医学与生物科学学院免疫学系,江苏苏州 215123;苏州大学医学部基础医学与生物科学学院免疫学系,江苏苏州 215123;苏州大学医学部基础医学与生物科学学院免疫学系,江苏苏州 215123;苏州市立医院消化疾病与营养研究中心,江苏苏州 215008【正文语种】中文【中图分类】R574【相关文献】1.葡聚糖硫酸钠(DSS)诱导的小鼠肠炎模型中CD19+CD5+CD1dhiB细胞的表达及抑炎作用 [J], 汪路曼;钱静;刘小明;常丽君;储以微2.小鼠葡聚糖硫酸钠结肠炎模型结肠黏膜中5-羟色胺及其转运蛋白的变化和意义[J], 张艳丽;王承党;余鸣秋3.葡聚糖硫酸钠诱导慢性溃疡性结肠炎小鼠模型的建立及评价 [J], 赵闪闪;黄雪;覃蒙斌;张君红;刘莹;井洁;蓝华4.葡聚糖硫酸钠自由饮用与灌胃诱导小鼠溃疡性结肠炎模型的比较 [J], 茶亚飞;郭雪艳;李宝晶;李艳平;王亭;毛晓健5.肝螺杆菌感染对葡聚糖硫酸钠诱导小鼠慢性结肠炎模型的影响 [J], 吴志浩;沈宸;殷俊;朱立麒;张泉因版权原因，仅展示原文概要，查看原文内容请购买。
NADPH氧化酶Nox2和Nox4在小鼠肠炎中的表达及意义肖中岳;轩青霞;高强【摘要】目的探讨烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶家族的主要成员NADPH 氧化酶2 (Nox2) 和Nox4 在小鼠肠炎模型结肠组织中的表达及意义.方法选用6 ～ 8周龄的129S /SV 雄性小鼠建立结肠炎模型,将其随机分为对照组、1. 5％葡聚糖硫酸钠(DSS) 组和3. 0％ DSS 组,对照组自由饮水,1. 5％ DSS 组和3. 0％DSS 组分别给予含 1. 5％ DSS 和3. 0％ DSS 饮用水自由饮用6 d.通过体质量变化、疾病活动指数(DAI) 评分和组织病理学评分等方法评估肠道炎症程度.使用酶标仪间接测定小鼠血清中丙二醛(MDA) 的含量,以评估实验小鼠的氧化应激程度.采用实时定量PCR 技术检测结肠组织中促炎因子白介素-1β (IL-1β)、白介素-6 (IL-6) 和肿瘤坏死因子-α (TNF-α) 以及Nox2 和Nox4 mRNA 表达情况;采用免疫组织化学法检测结肠组织中Nox2 和Nox4 蛋白表达情况.结果对照组小鼠未见肠炎表现,1. 5％ DSS 组小鼠呈轻度肠炎表现,3. 0％ DSS 组小鼠呈重度肠炎表现.杯状细胞在1. 5％ DSS 组体积增大、数量减少,在3. 0％ DSS 组进一步减少,甚至消失(均P < 0. 05).MDA 在1. 5％ DSS 组升高,在3. 0％ DSS 组进一步升高(均P < 0. 05).Nox2 和Nox4 mRNA 和蛋白的表达量在不同炎症程度时表达不同.两者mRNA 和蛋白的表达量一致,炎症组均显著高于对照组,且均随炎症程度增加表达进一步增加(均P < 0. 05).Nox2 蛋白主要表达于浸润的吞噬细胞和中性粒细胞等炎细胞中;Nox4 蛋白表达于中性粒细胞和淋巴细胞等炎细胞中.结论 Nox2 和Nox4在小鼠肠炎的发病过程中发挥重要作用.%Objective To investigate the expression and significance of NADPH oxidases Nox2 and Nox4 in mouse colitis. Methods Mouse colitis model was established by using six-to-eight-week-old 129S /SV mice. Mice were randomly divided into 3 groups:control group,1. 5％ dextran sulfate sodium (DSS) group and 3. 0％ DSS group (n = 10 for each group). All of them were fed for 7 days to adapt to the environment. After then,the control group was given drinking water only,colitis was induced by giving drinking water consisted of 1. 5％ DSS or 3. 0％ DSS for 6 days. Weight loss,disease activity index (DAI) and histology were used to quantify the severity of colon inflammation. Oxidative stress indicator,malondialdehyde (MDA) in serum was measured by biochemical methods. The mRNA levels of pro-inflammation cytokines (IL-1β,IL-6 and TNF-α) were quantified by real-time PCR. The protein and mRNA expression of Nox2 and Nox4 in colon tissue of mice was evaluated by immunohistochemistry and real-time PCR,respectively. Results There was no colitis in the control group,while mild and severe enteritis was found in mice in the 1. 5％ DSS group and 3. 0％ DSS group,respectively. The number of goblet cells was decreased significantly in the 1. 5％ DSS group than that of control group (P < 0. 05),and further reduced in the 3. 0％ DSS group (P < 0. 05). MDA was enhanced along with the increased concentration of DSS (P < 0. 05 for both). The expression of Nox2 and Nox4 protein and mRNA was different with the severity of inflammation. The expression of protein and mRNA of both Nox2 and Nox4 were increased in 1. 5％ DSS group compared with the control group (P < 0. 05),and further reduced in the 3. 0％ DSS group (P < 0. 05). Nox2 mostly expressed in the phagocytes and neutrophils; Nox4 mostly expressed in the neutrophils and lymphocytes. Conclusion Nox2 and Nox4 play an important role in the occurrence of mouse colitis.【期刊名称】《安徽医科大学学报》【年(卷),期】2019(054)002【总页数】6页(P225-230)【关键词】NADPH 氧化酶;Nox2;Nox4;炎症性肠病;结肠炎【作者】肖中岳;轩青霞;高强【作者单位】河南科技大学第一附属医院肿瘤科,洛阳 471003;洛阳市妇女儿童医疗保健中心,洛阳 471023;河南科技大学第一附属医院肿瘤科,洛阳 471003【正文语种】中文【中图分类】R574.62炎症性肠病 (inflammatory bowel disease, IBD) 包括克罗恩病和溃疡性结肠炎两种疾病，患者多反复出现腹痛、腹泻、黏液脓血便等症状[1]。
葡聚糖硫酸钠诱导不同性别溃疡性结肠炎小鼠模型的比较张琳珮;陆洪艳;史雯雪;蒋霞【期刊名称】《药品评价》【年(卷),期】2022(19)3【摘要】目的:探讨性别差异对小鼠溃疡性结肠炎(UC)模型成模的影响,为实验造模提供参考依据。
方法:将24只C57BL/6J小鼠根据性别随机分为4组,雌性对照组、雄性对照组、雌性DSS组和雄性DSS组,每组6只,对照组正常饮食,雌性或雄性DSS组给予正常饮食+3%葡聚糖硫酸钠(DSS)溶液自由饮用7 d进行造模。
每日记录各组小鼠精神状态、毛色光泽、体质量、进食量、粪便性状及隐血,评估疾病活动指数(DAI)、病死率、成模率、结肠长度、脾脏系数,苏木精-伊红(HE)染色观察结肠病理变化。
结果:雌性DSS组小鼠DAI评分、病死率均较雄性DSS组低,脾脏系数较雄性DSS组低(P<0.01),体质量变化、结肠长度缩短较雄性DSS组较少(P<0.01,P<0.05),成模率较雄性DSS组高,结肠病理变化较雄性DSS组黏膜充血水肿轻,炎症细胞较少。
结论:3% DSS溶液诱导C57BL/6J小鼠UC模型存在一定的性别偏倚,提示使用3% DSS溶液7 d建立雌性UC小鼠更易于模型的诱导。
【总页数】4页(P141-144)【作者】张琳珮;陆洪艳;史雯雪;蒋霞【作者单位】广西医科大学第一附属医院【正文语种】中文【中图分类】TP3【相关文献】1.葡聚糖硫酸钠诱导慢性溃疡性结肠炎小鼠模型的建立及评价2.3种浓度葡聚糖硫酸钠诱导小鼠溃疡性结肠炎模型的比较3.葡聚糖硫酸钠自由饮用与灌胃诱导小鼠溃疡性结肠炎模型的比较4.苦参及其不同炮制品水煎液对抗葡聚糖硫酸钠诱导的小鼠溃疡性结肠炎作用比较5.白芨多糖对葡聚糖硫酸钠诱导的小鼠溃疡性结肠炎治疗模型的优化和建立因版权原因，仅展示原文概要，查看原文内容请购买。
葡聚糖硫酸钠自由饮用与定量灌胃诱导小鼠急性结肠炎模型的比较研究黄循铷;王承党;王瑞幸【期刊名称】《胃肠病学》【年(卷),期】2009(14)1【摘要】背景:自由饮用葡聚糖硫酸钠(DSS)诱导的鼠类急性结肠炎模型均一性欠佳,动物死亡率较高.目的:评估2% DSS 自由饮用或定量灌胃诱导的小鼠急性结肠炎模型模拟人类溃疡性结肠炎(UC)的效果和均一性.方法:予ICR小鼠2% DSS自由饮用或定量灌胃建立急性结肠炎模型,检测并比较正常对照组和两组模型小鼠的症状出现时间和频率、疾病活动指数(DAI)、DSS消耗量、死亡率、结肠长度、结肠损伤大体评分(MACD)、结肠组织病理学表现以及外周血白细胞计数和分类.结果:两组模型小鼠均出现类似人类UC的症状和组织病理学改变,结肠显著短缩,DAI、MACD以及外周血白细胞计数和中性粒细胞百分比显著高于正常对照组.与DSS 自由饮用组相比,DSS定量灌胃组小鼠症状出现时间更为一致,症状出现率显著增高,动物死亡率和DSS消耗量显著减低.结论:2% DSS定量灌胃诱导的小鼠急性结肠炎模型能较稳定地模拟人类UC,均一性高,动物死亡率低.【总页数】4页(P27-30)【作者】黄循铷;王承党;王瑞幸【作者单位】福建医科大学附属第一医院消化内科,福建医科大学消化系病研究室,350005;福建医科大学附属第一医院消化内科,福建医科大学消化系病研究室,350005;福建医科大学生理学与病理生理学系【正文语种】中文【中图分类】R9【相关文献】1.葡聚糖硫酸钠诱导C57BL／6J小鼠急性结肠炎模型的建立与评价 [J], 徐丽红;肖芳;兰小琴;何嘉怡;丁强;田德安;郑勇2.CD8+T细胞在葡聚糖硫酸钠诱导的小鼠急性结肠炎中的致病性研究 [J], 曾群雄; 邓军; 沈南3.芦丁在葡聚糖硫酸钠诱导的小鼠急性结肠炎中的作用及其机制 [J], 褚旭芳;王笑楠;范秋灵;汪旭4.葡聚糖硫酸钠自由饮用与灌胃诱导小鼠溃疡性结肠炎模型的比较 [J], 茶亚飞;郭雪艳;李宝晶;李艳平;王亭;毛晓健5.金枪鱼骨胶原肽对葡聚糖硫酸钠诱导急性结肠炎小鼠的预防效果 [J], 舒聪涵;相兴伟;孙继鹏;王家星;廖妙飞;邓尚贵;周宇芳;郑斌因版权原因，仅展示原文概要，查看原文内容请购买。
