GSS改善慢性脑缺血小鼠肠道屏障功能紊乱的作用研究OA

Objective:The purpose of this study was to explore the protective effects of Genistein-3'-sodium sulfonate(GSS)on intestinal barrier function following chronic cerebral ischemia and its potential mechanisms,providing experimental evidence for promoting GSS's clinical translation.Methods:Chronic cerebral ischemia mice models were established by bilateral common carotid artery stenosis(BCCAS).The mice were divided into Sham control group,BCCAS model group,and BCCAS+GSS treatment group(1 mg/kg GSS).After 8 weeks,colon tissues of mice were collected,and HE staining and PAS staining were used to show the changes in the barrier structure and composition of colon tissues in each group of mice.Western blot was used to detect the expression levels of tight junction proteins Occludin,Claudin-5,and JAK2/STAT3 proteins(or phosphorylated proteins)in mice colon tissues.Results:HE staining:compared with the Sham group,the intestinal epithelial cells of the BCCAS group mice showed shedding and necrosis,villi became shorter,blunter and even disappeared,the mucosal layer became thinner,the submucosa was edematous,and muscle layer fibers were even broken.Glandular atrophy was also observed.However,compared with the BCCAS group,the degree of colonic epithelial structure damage in the BCCAS+GSS group mice was significantly reduced.PAS staining:compared with the Sham group,the mucosal layer of the intestinal wall in the BCCAS group mice became thinner or even absent,with a significant reduction in the number of goblet cells,local glandular atrophy,and a lighter PAS staining.In contrast,compared with the BCCAS group,the morphology and number of goblet cells in the colon of the BCCAS+GSS group mice were significantly improved,and the PAS staining became darker,suggesting an improvement in glycogen secretion function.WB detection results:compared with the Sham group,the expression of Claudin-5 and Occludin in the BCCAS group mice decreased,while the expression of p-JAK2/JAK2 and p-STAT3/STAT3 increased.Compared with the BCCAS group,the expression of Claudin-5 and Occludin in the BCCAS+GSS group mice increased,while the expression of p-JAK2/JAK2 and p-STAT3/STAT3 decreased,and the differences were statistically significant(P<0.05).Conclusion:GSS may improve intestinal barrier function in chronic cerebral ischemia mice by inhibiting the JAK2/STAT3 signaling pathway.