角质细胞生长因子-2对右旋葡聚糖硫酸钠诱导的小鼠结肠炎和肠道黏膜屏障的保护作用

目的探究角质细胞生长因子-2(keratinocyte growth factor 2,KGF-2)对右旋葡聚糖硫酸钠(dextran sodium sulfate,DSS)诱导的小鼠结肠炎和肠道黏膜屏障的保护作用及其作用机制。方法 36只C57BL/c雄性小鼠随机分为正常对照组、DSS模型组、中剂量KGF-2(5mg/kg)组和高剂量KGF-2(10mg/kg)组。除正常对照组外小鼠饮用水中均添加3.5%DSS,KGF-2组同时腹腔注射相应剂量的KGF-2。检测小鼠体重、疾病活动指数(disease activity index,DAI)、结肠长度缩短、结肠组织病理评分评价KGF-2对结肠炎...

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Published in复旦学报(医学版) Vol. 45; no. 1; pp. 1 - 8
Main Author 黄盈瑜;刘红春;宋元林;冯娜娜
Format Journal Article
LanguageChinese
Published 复旦大学附属中山医院消化科 上海200032%复旦大学附属中山医院呼吸科 上海200032 2018
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ISSN1672-8467
DOI10.3969/j.issn.1672-8467.2018.01.001

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Summary:目的探究角质细胞生长因子-2(keratinocyte growth factor 2,KGF-2)对右旋葡聚糖硫酸钠(dextran sodium sulfate,DSS)诱导的小鼠结肠炎和肠道黏膜屏障的保护作用及其作用机制。方法 36只C57BL/c雄性小鼠随机分为正常对照组、DSS模型组、中剂量KGF-2(5mg/kg)组和高剂量KGF-2(10mg/kg)组。除正常对照组外小鼠饮用水中均添加3.5%DSS,KGF-2组同时腹腔注射相应剂量的KGF-2。检测小鼠体重、疾病活动指数(disease activity index,DAI)、结肠长度缩短、结肠组织病理评分评价KGF-2对结肠炎的保护作用,多功能酶标仪检测血清异硫氰酸荧光素葡聚糖(fluorescein isothiocyanate-dextran,FITC-D)肠道渗透率,免疫组化和Western blot检测结肠组织ZO-1和occludin蛋白的表达,ELISA分析结肠组织匀浆的TNF-α、IL-6、IL-10、TGF-1β、IFN-γ、IL-1β浓度,以探讨KGF-2对肠道屏障功能保护作用机制。结果与DSS模型组相比,高剂量KGF-2组结肠DAI显著下降(P=0.021 1),体重减轻明显改善(P=0.017 6),HE评分显著降低(12.17±1.222vs.7.000±0.632 5,P=0.001 1),FITC-D渗透率显著降低(168.5±27.01 vs.14.62±1.812,P=0.004 7),结肠较长(4.956±0.2583 vs.6.289±0.2157,P=0.001 1);ZO-1(0.158 6±0.010 51 vs.0.387 9±0.028 64,P〈0.000 1)和occludin(0.300 5±0.026 56 vs.0.445 0±0.056 62,P=0.043 4)蛋白表达水平显著升高;肠道组织TNF-α表达显著降低(68.93±3.379 vs.40.41±1.576,P〈0.000 1),而IL-10(304.0±21.47 vs.521.2±49.40,P=0.002 4)和IL-6(3755±309.8 vs.5 640±418.0,P=0.004 7)的表达显著升高,疗效呈剂量依赖性。结论 KGF-2能够减轻DSS导致的肠道黏膜损伤,修复肠道黏膜屏障。KGF-2对肠道黏膜屏障的保护
Bibliography:HUANG Ying-yu1,LIU Hong-chun1 ,SONG Yuan-lin2, FENG Na-na2 (1 Department of Gastroenterology ,2 Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032. China )
keratinocyte growth factor 2; inflammatory bowel diseases; mucosal barrier;tight junction; cytokine
Objective To determine the protective role of keratinocyte growth factor 2(KGF-2)on dextran sodium sulfate(DSS)-induced murine colitis and investigate the mechanism of its effect on intestinal mucosal barrier.Methods A total of 36 male C57BL/c mice were divided into 4groups:normal control group,DSS model group,model+KGF-2(5mg/kg)group and model+KGF-2(10mg/kg)group.Groups except the control were added 3.5% DSS in drinking water.Disease activity index(DAI),weight change,colon length loss and histological score were detected to evaluate the protective effect of KGF-2on colitis.Serum fluorescein isothiocyanate-dextran(FITC-D)permeability were assayed by multiscan spectrum.In order to explore the protective role of KGF-2on murin
ISSN:1672-8467
DOI:10.3969/j.issn.1672-8467.2018.01.001