S100A4通過增加檸檬酸桿菌對腸上皮細胞的黏附促進結腸炎的發(fā)展
發(fā)布時間：2018-12-23 08:39
【摘要】：炎癥性腸病(Inflammatory bowel disease,IBD)是一類以慢性炎癥為特征的腸道炎癥疾病。引發(fā)該病癥的因素繁多,有效的宿主防御機制對于抵御IBD十分重要。S100A4是S100家族中的一員,在炎癥中的作用尚不清楚。因此,本試驗分別給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)的檸檬酸桿菌(Citrobacter rodentium,C.rodentium),建立腸炎模型。采用組織學、細胞學和分子生物學等技術方法探究S100A4在炎癥中的作用及分子機制。結果表明S100A4在C.rodentium誘導的小鼠腸炎模型中的表達顯著上調(P0.01)。S100A4-/-小鼠相對于WT小鼠體重下降不明顯(P0.01),結腸病理損傷程度減輕(P0.05),結腸中趨化因子和促炎因子的表達顯著下調(P0.05),結腸炎癥細胞的浸潤減少(P0.01),結腸炎癥相關蛋白p65的磷酸化水平顯著下調。說明S100A4能夠促進結腸炎的發(fā)展。S100A4-/-小鼠結腸Ki-67的陽性細胞率顯著下降(P0.05);WT小鼠結腸中增殖相關蛋白Stat3、Erk的磷酸化水平顯著上調。說明S100A4促進C.rodentium誘導的小鼠結腸上皮細胞的增殖。進一步研究發(fā)現S100A4能夠增加C.rodentium對小鼠結腸和CT26細胞的黏附(P0.05);整合素β1(Integrinβ1)在WT小鼠結腸中和S100A4蛋白處理的CT26細胞中的表達顯著上調(P0.05)。上述結果說明S100A4能夠通過上調Integrinβ1的表達增加C.rodentium對腸道上皮細胞的黏附,從而促進結腸炎的發(fā)展。本實驗為探究S100A4在結腸炎中的作用及機制提供了可信的理論依據,可為相關科學研究及醫(yī)學臨床治療提供參考。
[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.
【學位授予單位】：東北師范大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R574.62
本文編號：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.
【學位授予單位】：東北師范大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R574.62
【參考文獻】
相關期刊論文 前1條
1 胡仁偉;歐陽欽;陳曦;常玉英;白愛平;王瑞華;張虎;;近15年我國炎癥性腸病文獻分析[J];胃腸病學;2007年02期
，本文編號：2389712
本文鏈接：http://lk138.cn/yixuelunwen/xiaohjib/2389712.html
最近更新
教材專著
