榴莲壳多糖对葡聚糖硫酸钠诱导的小鼠结肠炎的改善作用及机制研究

Ameliorative effect and mechanism of durian shell polysaccharide on dextran sodium sulfate-induced colitis in mice

该文采用葡聚糖硫酸钠(dextran sodium sulfate,DSS)建立小鼠溃疡性结肠炎模型,用美沙拉嗪[mesalazine,200 mg/(kg·d)]和榴莲壳多糖[250 mg/(kg·d)、500 mg/(kg·d)、1000 mg/(kg·d)]进行干预,检测小鼠体重变化、疾病活动指数(disease activity index,DAI)、结肠长度;使用髓过氧化物酶(myeloperoxidase,MPO)试剂盒测定结肠组织中MPO活性;ELISA法检测炎症因子表达水平;苏木精伊红染色(hematoxylin and eosin staining,H&E)观察结肠组织病理变化,综合评价榴莲壳多糖对小鼠溃疡性结肠炎的保护作用及其作用机制。与DSS组相比,榴莲壳多糖高剂量干预组小鼠体重和结肠长度增加、DAI和结肠重量降低,促炎因子表达水平显著降低(P<0.01),炎性标志物MPO显著降低(P<0.01);与模型组比较,榴莲壳多糖组小鼠肠组织ZO-1、occludin、Claudin-7及E-cadherin蛋白表达水平呈剂量依赖性增加(P<0.05),N-cadherin蛋白表达水平呈剂量依赖性降低(P<0.05),结肠上皮结构改善;在细胞模型中,榴莲壳多糖通过上调E-cadherin蛋白表达水平和下调N-cadherin的蛋白表达水平来修复黏膜损伤并减轻肠道炎症。榴莲壳多糖能改善DSS诱导的小鼠肠黏膜损伤和抗肿瘤坏死因子-α(tumor necrosis factorα,TNF-α)诱导的Caco-2细胞上皮屏障功能障碍,对溃疡性结肠炎具有良好的保护作用。

This paper used dextran sodium sulfate(DSS)to establish a mouse model of ulcerative colitis,which was intervened with mesalazine[200 mg/(kg·d)]and durian shell polysaccharide[250 mg/(kg·d),500 mg/(kg·d),1000 mg/(kg·d)]to detect changes in body weight,disease activity index(DAI),and colon length in mice.Myeloperoxidase(MPO)activity in colonic tissue was determined by using an MPO kit.Inflammatory cytokines were evaluated by ELISA.The histopathological changes of the colon were observed by HE staining,and the protective effect of durian shell polysaccharide on ulcerative colitis in mice and its mechanism of action were comprehensively evaluated.Compared with the DSS group,mice in the durian shell polysaccharide high-dose intervention group had increased body weight and colon length,decreased DAI and colon weight,significantly lowered expression levels of pro-inflammatory factors(P<0.01),and significantly lowered inflammatory marker MPO(P<0.01).Compared with the model group,the expression levels of ZO-1,occludin,claudin-7,and E-cadherin in the intestinal tissue of mice in the durian shell polysaccharide group showed a dose-dependent increase(P<0.05)and a dose-dependent decrease(P<0.05)in the expression level of N-cadherin protein,and the colonic epithelial structure was improved.In a cellular model,durian shell polysaccharide repaired mucosal damage and reduced intestinal inflammation by upregulating E-cadherin protein expression levels and downregulating N-cadherin protein expression levels.Durian shell polysaccharide improves DSS-induced intestinal mucosal injury in mice and TNF-α-induced epithelial barrier dysfunction in Caco-2 cells and has good protective effects against ulcerative colitis.