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真人养脏汤对溃疡性结肠炎大鼠肠道黏膜屏障功能的保护作用 被引量:25

Protective effect of Zhenrenyangzang decoction on intestinal mucosal barrier function in ulcerative colitis rats
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摘要 目的:观察真人养脏汤(ZRYZ)对三硝基苯磺酸(TNBS)诱导的溃疡性结肠炎(UC)大鼠肠道黏膜屏障功能的保护作用以及紧密连接相关蛋白闭锁小带蛋白1(zonula occludens-1,ZO-1)和闭锁蛋白(occludin)的表达变化,探讨其可能作用机制。方法:将Wistar雄性大鼠随机分为正常组、模型组、柳氮磺吡啶(SASP)阳性对照组、ZRYZ高剂量组和ZRYZ低剂量组。除正常组外,其它各组用TNBS/50%乙醇混合溶液局部灌肠法复制溃疡性结肠炎大鼠模型。造模成功后阳性对照组给予SASP混悬液灌胃;ZRYZ高剂量组和ZRYZ低剂量组分别按生药30.4 g/kg和15.2 g/kg剂量灌胃;正常组与模型组等量生理盐水灌胃,共21 d。给药结束后,考察大鼠疾病活动指数(DAI)变化,进行大体损伤评分,测定肠道黏膜通透性(以尿中乳果糖/甘露醇的比值表示,即L/M值),测定结肠组织髓过氧化物酶(MPO)活性,计数结肠组织杯状细胞数量,测定血清二胺氧化酶(DAO)及D-乳酸(D-LA)水平,检测ZO-1和occludin的表达。结果:与正常组相比,模型组DAI、大体损伤评分、L/M值、结肠组织MPO活性以及血清D-LA和DAO水平明显升高(P<0.05),结肠组织杯状细胞数量以及ZO-1和occludin表达明显降低(P<0.05);与模型组相比,ZRYZ高剂量组和ZRYZ低剂量组DAI、大体损伤评分、L/M值、结肠组织MPO活性以及血清DAO和D-LA水平明显降低(P<0.05),结肠组织杯状细胞数量以及ZO-1和occludin表达明显升高(P<0.05)。结论:真人养脏汤可通过降低肠道黏膜通透性,保护溃疡性结肠炎大鼠肠道上皮细胞黏膜屏障功能,其机制可能与升高ZO-1和occludin表达有关。 AIM:To investigate the protective effect of Zhenrenyangzang decoction(ZRYZ) on the intestinal mucosal barrier function and the expression of tight junction proteins,zonula occludens-1(ZO-1) and occludin,in the colon of rats with trinitrobenzenesulfonic acid(TNBS)-induced ulcerative colitis in order to explore the possible mechanism involved.METHODS:Male Wistar rats were randomly divided into normal group,model group,salazosulfapyridine(SASP) positive control group,high-dose ZRYZ(ZRYZ-H) group and low-dose ZRYZ(ZRYZ-L) group.Except the normal group,the rats in other groups were given the TNBS/50% ethanol mixed solution by enema to make the ulcerative colitis model.The rats in positive control group were given SASP suspension liquid.The rats in ZRYZ-H group and ZRYZ-L group were orally administered with ZRYZ at doses of 30.4 g/kg and 15.2 g/kg,respectively,while the rats in normal group and model group were orally administered with saline.All the drugs were administered to the rats for consecutive 21 d.Disease activity index(DAI) was investigated during the drug treatment,and colon samples were collected after drug administration for evaluating morphological damage score.Intestinal mucosal permeability was measured by detection of lactulose/mannitol(L/M) in urine.Colonic myeloperoxidase(MPO) activity and goblet cell number,serum diamine oxidase(DAO) and D-lactic acid(D-LA) levels,and the colonic expression of ZO-1 and occludin were also measured.RESULTS:Compared with normal group,DAI,morphological damage score,L/M value,colonic MPO activity as well as serum D-LA and DAO levels in model group significantly increased(P 〈 0.05),while goblet cell number as well as the expression levels of ZO-1 and occludin in model group were significantly reduced(P 〈 0.05).Compared with model group,DAI,morphological damage score,L/M value,colonic MPO activity as well as serum DAO and D-LA levels in ZRYZ-H group and ZRYZ-L group were reduced significantly(P 〈 0.05),whi
出处 《中国病理生理杂志》 CAS CSCD 北大核心 2017年第11期2053-2059,共7页 Chinese Journal of Pathophysiology
基金 黑龙江省教育厅科学技术研究项目(No.12531798)
关键词 真人养脏汤 溃疡性结肠炎 黏膜屏障 闭锁小带蛋白1 闭锁蛋白 Zhenrenyangzang decoction Ulcerative colitis Mucosal barrier Zonula occludens-1 Occludin
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