S100A4通过增加柠檬酸杆菌对肠上皮细胞的黏附促进结肠炎的发展
发布时间：2018-12-23 08:39
【摘要】：炎症性肠病(Inflammatory bowel disease,IBD)是一类以慢性炎症为特征的肠道炎症疾病。引发该病症的因素繁多,有效的宿主防御机制对于抵御IBD十分重要。S100A4是S100家族中的一员,在炎症中的作用尚不清楚。因此,本试验分别给S100A4基因敲除小鼠(S100A4-/-)和野生型小鼠(Wild type,WT)灌胃2×109 CFU(Colony-forming unit,CFU)的柠檬酸杆菌(Citrobacter rodentium,C.rodentium),建立肠炎模型。采用组织学、细胞学和分子生物学等技术方法探究S100A4在炎症中的作用及分子机制。结果表明S100A4在C.rodentium诱导的小鼠肠炎模型中的表达显著上调(P0.01)。S100A4-/-小鼠相对于WT小鼠体重下降不明显(P0.01),结肠病理损伤程度减轻(P0.05),结肠中趋化因子和促炎因子的表达显著下调(P0.05),结肠炎症细胞的浸润减少(P0.01),结肠炎症相关蛋白p65的磷酸化水平显著下调。说明S100A4能够促进结肠炎的发展。S100A4-/-小鼠结肠Ki-67的阳性细胞率显著下降(P0.05);WT小鼠结肠中增殖相关蛋白Stat3、Erk的磷酸化水平显著上调。说明S100A4促进C.rodentium诱导的小鼠结肠上皮细胞的增殖。进一步研究发现S100A4能够增加C.rodentium对小鼠结肠和CT26细胞的黏附(P0.05);整合素β1(Integrinβ1)在WT小鼠结肠中和S100A4蛋白处理的CT26细胞中的表达显著上调(P0.05)。上述结果说明S100A4能够通过上调Integrinβ1的表达增加C.rodentium对肠道上皮细胞的黏附,从而促进结肠炎的发展。本实验为探究S100A4在结肠炎中的作用及机制提供了可信的理论依据,可为相关科学研究及医学临床治疗提供参考。
[Abstract]:Inflammatory bowel disease (Inflammatory bowel disease,IBD) is a kind of intestinal inflammatory disease characterized by chronic inflammation. There are many factors contributing to the disease, and effective host defense mechanisms are important to resist IBD. S100A4 is a member of the S100 family and its role in inflammation is unclear. Therefore, the S100A4 knockout mice (S100A4-r-) and the wild-type mice (Wild type,WT) were given intragastric administration of 2 脳 10 ~ 9 CFU (Colony-forming unit,CFU) citrate bacilli (Citrobacter rodentium,C.rodentium) to establish enteritis models. The role and molecular mechanism of S100A4 in inflammation were investigated by means of histology, cytology and molecular biology. The results showed that the expression of S100A4 was significantly up-regulated in C.rodentium induced mouse enteritis (P0.01), the weight loss of S100A4-r-m- mice was not significant compared with that of WT mice (P0.01), and the degree of colonic pathological injury was decreased (P0.05). The expression of chemokines and pro-inflammatory factors in colon was significantly down-regulated (P0.05), the infiltration of colitis cells was decreased (P0.01), and the phosphorylation level of p65 was significantly down-regulated. The results showed that S100A4 could promote the development of colitis. The positive rate of Ki-67 in S100A4-r-mouse colon decreased significantly (P0.05) the phosphorylation level of proliferation-associated protein Stat3,Erk in colon of); WT mice was up-regulated. The results showed that S100A4 promoted the proliferation of mouse colon epithelial cells induced by C.rodentium. Further studies showed that S100A4 could increase the adhesion of C.rodentium to mouse colon and CT26 cells (P0.05), and the expression of integrin 尾 1 (Integrin 尾 1) in WT mice colon and CT26 cells treated with S100A4 protein was significantly up-regulated (P0.05). These results suggest that S100A4 can promote the development of colitis by upregulating the expression of Integrin 尾 1 and increasing the adhesion of C.rodentium to intestinal epithelial cells. This study provides a reliable theoretical basis for exploring the role and mechanism of S100A4 in colitis, and provides a reference for related scientific research and medical clinical treatment.
【学位授予单位】：东北师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R574.62
本文编号：2389712
[Abstract]:Inflammatory bowel disease (Inflammatory bowel disease,IBD) is a kind of intestinal inflammatory disease characterized by chronic inflammation. There are many factors contributing to the disease, and effective host defense mechanisms are important to resist IBD. S100A4 is a member of the S100 family and its role in inflammation is unclear. Therefore, the S100A4 knockout mice (S100A4-r-) and the wild-type mice (Wild type,WT) were given intragastric administration of 2 脳 10 ~ 9 CFU (Colony-forming unit,CFU) citrate bacilli (Citrobacter rodentium,C.rodentium) to establish enteritis models. The role and molecular mechanism of S100A4 in inflammation were investigated by means of histology, cytology and molecular biology. The results showed that the expression of S100A4 was significantly up-regulated in C.rodentium induced mouse enteritis (P0.01), the weight loss of S100A4-r-m- mice was not significant compared with that of WT mice (P0.01), and the degree of colonic pathological injury was decreased (P0.05). The expression of chemokines and pro-inflammatory factors in colon was significantly down-regulated (P0.05), the infiltration of colitis cells was decreased (P0.01), and the phosphorylation level of p65 was significantly down-regulated. The results showed that S100A4 could promote the development of colitis. The positive rate of Ki-67 in S100A4-r-mouse colon decreased significantly (P0.05) the phosphorylation level of proliferation-associated protein Stat3,Erk in colon of); WT mice was up-regulated. The results showed that S100A4 promoted the proliferation of mouse colon epithelial cells induced by C.rodentium. Further studies showed that S100A4 could increase the adhesion of C.rodentium to mouse colon and CT26 cells (P0.05), and the expression of integrin 尾 1 (Integrin 尾 1) in WT mice colon and CT26 cells treated with S100A4 protein was significantly up-regulated (P0.05). These results suggest that S100A4 can promote the development of colitis by upregulating the expression of Integrin 尾 1 and increasing the adhesion of C.rodentium to intestinal epithelial cells. This study provides a reliable theoretical basis for exploring the role and mechanism of S100A4 in colitis, and provides a reference for related scientific research and medical clinical treatment.
【学位授予单位】：东北师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R574.62
【参考文献】
相关期刊论文 前1条
1 胡仁伟;欧阳钦;陈曦;常玉英;白爱平;王瑞华;张虎;;近15年我国炎症性肠病文献分析[J];胃肠病学;2007年02期
，本文编号：2389712
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