β-arrestin2通过破坏肠上皮屏障功能而促进小鼠肠炎

β-arrestin2 promoting mice colitis through impairment of epithelial barrier function

目的观察β-arrestin2对小鼠肠炎进展的影响,并从肠上皮屏障功能方面探讨β-arrestin2作用机制。方法用葡聚糖硫酸钠(DSS)制备小鼠急性肠炎模型,将实验对象分为3组:野生型对照(WT)组、野生型肠炎(WT+DSS)组和β-arrestin2^(-/-)肠炎(KO+DSS)组。比较β-arrestin2在WT组和WT+DSS组结肠中m RNA和蛋白表达水平;比较WT+DSS组和KO+DSS组的体重下降程度、疾病活动指数、脾脏重量、结肠长度及病理学表现、肠上皮FITC-D渗透率及紧密连接蛋白(occludin,claudin1,ZO-1)表达水平。结果β-arrestin2在WT+DSS组小鼠结肠中的m RNA和蛋白水平高于WT组;相比于WT+DSS组,KO+DSS组体重下降程度小(P<0.05),疾病活动度轻(P<0.05),脾脏肿大和结肠缩短程度小,病理学评分更低(P=0.002),肠上皮渗透率更低(P=0.009),occludin和claudin1蛋白表达水平更高,ZO-1在两组间无明显差异。结论β-arrestin2可能通过破坏肠上皮屏障而促进小鼠肠炎。

Objective To investigate the role ofβ?arrestin2in intestinal inflammation and illustrate the mechanisms from the perspective of epithelial barrier function.Methods Dextran sodium sulfate(DSS)is used to induce acute intestinal colitis in mice.The experiment groups are designed as the wild type control(WT),the wild type colitis(WT+DSS)and theβ-arrestin2-knockout colitis(KO+DSS).The expression ofβ-arrestin2gene by mRNA and protein level is compared between the WT and WT+DSS groups.The difference of weight loss,disease activity index(DAI),spleen weight,colon length,histological score,intestinal permeability and important tight junction proteins(occludin,claudin1and ZO-1)were detected in the WT+DSS and KO+DSS groups.Results Compared with the WT group,the expression ofβ-arrestin2was significantly higher in the colon of the WT+DSS group.Compared with the WT+DSS group,the KO+DSS group had less weight loss(P<0.05),lower DAI(P<0.05),smaller spleen,longer colon and lower histological score(P=0.002).The KO+DSS group had a lower intestinal permeability(P=0.009)and higher protein level of occludin and claudin1.There was no significant difference of ZO?1in the two groups.Conclusionβ?arrestin2may promote mouse colitis through impairment of epithelial barrier function.