摘要
目的研究栀子苷治疗溃疡性结肠炎(UC)模型大鼠的效果及其分子机制。方法将60只SPF级的雄性Sprague-Dawley(SD)大鼠随机分入对照组、模型组、栀子苷组、吡咯烷二硫代氨基甲酸铵(PDTC)组、VX765组,后四组采用三硝基苯磺酸(TNBS)灌肠的方式建立UC模型,每组12只。模型组给予0.9%氯化钠溶液灌胃、栀子苷组给予栀子苷灌胃、PDTC组给予NF-κB抑制剂PDTC腹腔内注射、VX765组给予NOD样受体蛋白3(NLRP3)炎性小体抑制剂VX765腹腔内注射。常规饲养14 d后处死,留取外周血和肠黏膜。比较各组大鼠体重、摄食量,血清二胺氧化酶、D-乳酸含量,肠黏膜内炎性细胞因子含量及其mRNA表达量,以及连接蛋白、NF-κB通路相关分子、NLRP3炎性小体的蛋白质表达量。结果栀子苷组、PDTC组、VX765组大鼠的体重、摄食量均显著高于模型组(P值均<0.05);血清中二胺氧化酶、D-乳酸和肠黏膜内TNF-α、IL-1、IL-18的含量均低于模型组(P值均<0.05);肠黏膜内闭锁小带蛋白-1(ZO-1)、闭合蛋白(Occludin)、密封蛋白-1(Claudin-1)的蛋白质表达水平均明显高于模型组(P值均<0.05)。栀子苷组、PDTC组肠黏膜内TNF-α、IL-1、IL-18的mRNA表达量均显著低于模型组(P值均<0.05),VX765组肠黏膜内TNF-α、IL-1、IL-18的mRNA表达量与模型组间的差异均无统计学意义(P值均>0.05)。结论栀子苷能够通过抑制NF-κB通路和NLRP3炎性小体所介导的炎性反应治疗UC模型大鼠。
Objective To study the effect of geniposide on ulcerative colitis(UC)in model rats and its molecular mechanism.Methods Sixty specific pathogen free(SPF)grade male Sprague-Dawley(SD)rats were randomly divided into five groups(n=12,respectively):control group,model group,geniposide group,pyrrolidine dithiocarbamate(PDTC)group and VX765 group.In the latter four groups,UC model was established by enema with trinitrobenzenesulfonic(TNBS)acid.Normal saline was intragastrically administered in the model group,and geniposide was intragastrically given in the geniposide group.PDTC,a nuclear factorκB(NF-κB)inhibitor was intraperitoneally injected in the PDTC group,and the VX765 group was intervened with NOD-like receptor protein 3(NLRP3)inflammasome inhibitor VX765.The samples of peripheral blood and intestinal mucosa were collected after 14-day feeding.The body weight,food intake,the contents of serum diamine oxidase and D-lactic acid,the contents and mRNA expression levels of inflammatory cytokines,protein expression of connexin,NF-κB pathway molecule and NLRP3 inflammatory body were compared between groups.Results Compared with those in the model group,the body weight,food intake,and protein expression levels of zonula occludens-1(ZO-1),Occludin and Claudin-1 in intestinal mucosa were significantly increased in the geniposide group,PDTC group and VX765 group,while the contents of diamine oxidase and D-lactic acid in serum and the contents of TNF-α,IL-1 and IL-18 in intestinal mucosa were significantly decreased(all P<0.05).The mRNA expression levels of TNF-α,IL-1 and IL-18 in intestinal mucosa of geniposide group and PDTC group was significantly lower than those of model group(all P<0.05).But there was no significant difference in the three parameters between VX765 group and model group(all P>0.05).Conclusion Geniposide can play a therapeutic role in UC through inhibiting the inflammatory response mediated by NF-κB pathway and NLRP3 inflammasome.
作者
步楠
范彦秋
BU Nan;FAN Yanqiu(Department of Gastroenterology,The Central Hospital of Jiamusi City,Jiamusi 154002,Heilongjiang,China)
出处
《上海医学》
CAS
北大核心
2019年第11期662-668,共7页
Shanghai Medical Journal
基金
黑龙江省卫生和计划生育委员会科研课题(2016-338).
作者简介
通信作者:步楠,电子邮箱为bunan886@163.com
