文献类型：期刊文献

中文题名：基于NLRP3/Caspase-1/GSDMD信号通路研究乌梅丸对溃疡性结肠炎小鼠结肠上皮细胞焦亡的作用机制

英文题名：Mechanism of Wumei Wan on colonic epithelial cell pyroptosis in mice with ulcerative colitis based on NLRP3/Caspase-1/GSDMD signaling pathway

作者：赵冠宇[1];辛蕊华[3];仇正英[3];石磊[1];王瑞琼[1,2];邵晶[1,2];吴国泰[1,2];杜丽东[1,2]

第一作者：赵冠宇

机构：[1]甘肃中医药大学药学院,甘肃兰州730000;[2]陇药产业创新研究院,甘肃兰州730000;[3]中国农业科学院兰州畜牧与兽药研究所,甘肃兰州730050

第一机构：甘肃中医药大学药学院（西北中藏药协同创新中心办公室）

年份：2023

卷号：54

期号：24

起止页码：8086

中文期刊名：中草药

外文期刊名：Chinese Traditional and Herbal Drugs

收录：CSTPCD;;Scopus;北大核心:【北大核心2020】；CSCD:【CSCD2023_2024】；

基金：甘肃省自然科学基金资助项目(20JR10RA317,22JR5RA038,22JR5RA041);甘肃省中医药研究中心开放课题(ZYZX-2020-20);甘肃省中医药科研立项课题资助项目(GZK-2019-23)。

语种：中文

中文关键词：乌梅丸;溃疡性结肠炎;核苷酸结合寡聚化结构域样受体蛋白3炎症小体;细胞焦亡;肠黏膜通透性;盐酸黄柏碱;盐酸黄连碱;盐酸小檗碱

外文关键词：Wumei Wan;ulcerative colitis;nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome;pyroptosis;intestinal mucosal permeability;phellodendrine chloride;coptisine hydrochloride;berberine

摘要：目的 研究乌梅丸对葡聚糖硫酸钠(dextran sulfate sodium salt,DSS)诱导的小鼠溃疡性结肠炎(ulcerative colitis,UC)的治疗作用及其通过介导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)/半胱氨酸天冬氨酸蛋白酶-1(cystein-asparate protease-1,Caspase-1)/消皮素D(gasdermin D,GSDMD)信号通路对结肠上皮细胞焦亡的影响。方法 自由饮用2%DSS构建UC小鼠模型,ig乌梅丸水煎液治疗,持续7 d,记录小鼠体质量变化和便血情况,分离完整结肠测量长度;苏木素-伊红(HE)染色观察结肠组织病理变化;TUNEL染色检测结肠上皮细胞损伤情况;ELISA法检测小鼠血清二胺氧化酶(diamine oxidase,DAO)活性和白细胞介素-18(interleukin-18,IL-18)、IL-1β含量;qRT-PCR法检测结肠组织Occludin-1、IL-18、IL-1β、NLRP3、Caspase-1和GSDMD m RNA表达;Western blotting检测结肠组织Occludin-1、NLRP3、Caspase-1和GSDMD-N蛋白表达。结果 与模型组比较,乌梅丸能减缓小鼠体质量下降,抑制结肠缩短、减轻结肠病理损伤,并且降低肠黏膜通透性,减少外周血和结肠组织中IL-1β、IL-18表达(P<0.05、0.01),降低结肠上皮细胞焦亡相关因子NLRP3、Caspase-1、GSDMD mRNA和蛋白表达(P<0.01)。结论 乌梅丸对DSS诱导的UC小鼠具有治疗作用,其作用机制与下调NLRP3/Caspase-1/GSDMD通路、抑制结肠上皮细胞焦亡有关。
Objective To investigate the therapeutic effect of Wumei Wan(乌梅丸)on dextran sulfate sodium salt(DSS)-induced ulcerative colitis(UC)in mice and its effect on nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/cysteinasparate protease-1(Caspase-1)/gasdermin D(GSDMD)signaling pathway-mediated colonic epithelial cell pyroptosis.Methods UC mouse model was induced by drinking 2%DSS freely,and treated with aqueous decoction of Wumei Wan for seven consecutive days.Weight changes and blood in stool of mice were recorded.The complete colon was isolated to measure the length.The histopathological changes of colon was observed by hematoxylin-eosin(HE)staining.The colonic epithelial cell damage were observed by TUNEL staining.The diamine oxidase(DAO)activity,interleukin-18(IL-18)and IL-1βlevels in serum of mice were detected by ELISA.The mRNA expression levels of Occludin-1,IL-18,IL-1β,NLRP3,Caspase-1 and GSDMD in colon tissue were detected by qRT-PCR.The protein expressions of Occludin-1,NLRP3,Caspase-1 and GSDMD-N in colon tissues were detected by Western blotting.Results Compared with model group,Wumei Wan slowed down weight loss,inhibited colonic shortening,attenuated pathological damage to the colon,reduced intestinal mucosal permeability,decreased the expressions of IL-1βand IL-18 in blood and colon tissues(P<0.05,0.01),and decreased the expressions of colonic epithelial cell pyroptosis-related factors NLRP3,Caspase-1 and GSDMD genes and proteins in mice(P<0.01).Conclusion Wumei Wan has therapeutic effects on DSS-induced UC mice,and its mechanism is related to inhibiting the NLRP3/Caspase-1/GSDMD pathway and decreasing colonic epithelial cell pyroptosis.