目的:初步探讨五味子甲素(schizandrin A,SchA)对腹泻型肠易激综合征(diarrhea-predominant ir?ritable bowel syndrome,IBS-D)大鼠肠上皮黏膜屏障功能的保护作用及其机制.方法:通过番泻叶灌胃联合肢体束缚法构建IBS-D大鼠模型.将大鼠分为3组(每组10只):对照组、模型组和SchA组(灌胃40 mg/kg SchA,每天1次,持续2周).腹部撤离反射(abdominal withdrawal reflex,AWR)试验评估大鼠肠痛觉敏感性;异硫氰酸荧光素标记葡聚糖(fluorescein isothiocyanate-dextran,FITC-dextran)法评估肠道通透性;苏木精-伊红(hematoxylin-eosin,HE)染色观察结肠黏膜组织形态表现;免疫组织化学和Western blot检测结肠组织中闭锁小带蛋白1(zonula occludens-1,ZO-1)和闭合蛋白(occludin)的蛋白表达情况;末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(terminal deoxynucleo?tidyl transferase-mediated dUTP nick-end labeling,TUNEL)染色和胱天蛋白酶3剪切片段(cleaved caspase-3)染色观察结肠黏膜中细胞凋亡情况;CD68染色和CD11b染色观察结肠黏膜中炎症细胞浸润情况;酶联免疫吸附试验(en?zyme-linked immunosorbent assay,ELISA)法检测结肠组织中炎症因子[白细胞介素6(interleukin-6,IL-6)、IL-1β及肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)]水平;Western blot法检测核苷酸结合寡聚化结构域样受体蛋白3(nucleotide-binding oligomerization domain-like receptor protein 3,NLRP3)炎症小体通路相关蛋白的表达情况.结果:与模型组比较,SchA组大鼠肠AWR痛觉阈值显著增高(P<0.05),肠道通透性显著降低(P<0.01),结肠黏膜组织形态得到改善,结肠组织中ZO-1和occludin表达水平显著增加(P<0.01),细胞凋亡比例显著降低(P<0.01),炎症细胞减少,炎症因子(IL-6、IL-1β及TNF-α)水平显著降低(P<0.01),NLRP3、含caspase募集结构域的凋亡相关斑点样蛋白(apoptosis-associated speck-like protein containing a caspase recruitment domain,ASC)和caspase-1的表达水平均显著降低(P<0.01).结论:SchA可改善IBS-D大鼠肠上皮黏膜屏障功能.

五味子甲素;腹泻型肠易激综合征;肠黏膜屏障;炎症;NLRP3炎症小体

齐齐哈尔医学院附属第二医院药学部,黑龙江齐齐哈尔161006

[1]耿峰;毛颖;丛珊;杜娟;于春雪-.五味子甲素对腹泻型肠易激综合征大鼠肠上皮黏膜屏障功能的保护作用)[J].中国病理生理杂志,2022(07):1266-1273

schizandrin,SchA,ritable,deoxynucleo,tidyl

五味子甲素,腹泻型肠易激综合征,肠易激综合征大鼠,黏膜屏障功能,diarrhea,predominant,ir,bowel,syndrome,IBS,番泻叶,灌胃,大鼠模型,撤离,abdominal,withdrawal,reflex,AWR,痛觉敏感性,异硫氰酸荧光素,荧光素标记,葡聚糖,fluorescein,isothiocyanate,dextran,FITC,肠道通透性,苏木,木精,伊红,hematoxylin,eosin,HE,肠黏膜组织,组织形态,免疫组织化学,blot,结肠组织,闭锁,zonula,occludens,ZO,闭合蛋白,occludin,脱氧核苷,转移酶,dUTP,末端标记,terminal,transferase,mediated,nick,end,labeling,TUNEL,胱天蛋白酶,cleaved,caspase,CD68,CD11b,炎症细胞浸润,酶联免疫吸附试验,zyme,linked,immunosorbent,assay,interleukin,tumor,necrosis,核苷酸结合寡聚化结构域样受体蛋白,nucleotide,binding,oligomerization,domain,like,receptor,protein,NLRP3,炎症小体,痛觉阈值,募集,集结,凋亡相关斑点样蛋白,apoptosis,associated,speck,containing,recruitment,ASC,肠黏膜屏障

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