肝细胞核因子4α在实验性结肠炎中的表达及意义

Expression of hepatocyte nuclear factor 4α in experimental colitis in mice

目的:通过检测肝细胞核因子4α(HNF4α)在小鼠实验性结肠炎肠组织中表达水平,探讨其在溃疡性结肠炎(UC)发病过程中的作用及意义。方法:分别采用2%和2.5%的葡聚糖硫酸钠(DSS)溶液诱导BALB/c小鼠急性结肠炎模型,以疾病活动指数(DAI)、组织学损伤及炎症细胞因子表达水平评价炎症严重程度。分析HNF4α表达水平与结肠炎严重程度及内皮型钙黏蛋白(E-CAD)、连接黏附分子1(JAM-1)和桥粒糖蛋白2(DSC-2)表达的相关性。结果:与正常对照组相比,DSS处理组小鼠DAI、组织学损伤及炎症因子表达显著增高(P<0.05),结肠黏膜中HNF4α蛋白及mRNA表达显著降低(P<0.01)。相关性分析结果提示HNF4α蛋白表达与DAI及组织学损伤程度呈负相关(P<0.01),HNF4αmRNA表达与E-CAD、JAM-1和DSC-2 mRNA表达呈正相关(P<0.01)。结论:HNF4α表达水平与实验性结肠炎严重程度及细胞间连接蛋白表达密切相关,提示HNF4α低表达可削弱肠道黏膜屏障功能,从而促进UC的发生发展。

AIM ： To investigate the role of hepatocyte nuclear factor 4or （HNF4a） in the pathogenesis of ul- cerative colitis （UC） by measuring the expression of HNF4a in the colon tissues in experimental colitis mice. METH- ODS： BALB/c mice were exposed to 2% or 2.5% （W/V） dextran sulfate sodium （DSS） to induce acute colitis, and the severity of colitis was assessed by observation of disease activity index （DAI）, histological injuries and inflammatory cyto- kines. The correlation between the expression of HNF4a and the severity of disease as well as E-cadherin （ E-CAD）, junc- tional adhesion molecule 1 （JAM-1） and desmocollin 2 （DSC-2） was analyzed. RESULTS： Compared with the normal controls, DAI, histological injuries and the mRNA expression of inflammatory eytokines in DSS-treated mice were signifi- cantly elevated （P 〈 0.05 ）. The expression of HNF4a at protein and mRNA levels was significantly decreased （ P 〈 0. 01 ）. The result of Pearson analysis indicated an inverse correlation between the protein expression of HNF4a and the se- verity of disease （P 〈 0.01 ）. The positive correlation between the mRNA expression of HNF4a and E-CAD/JAM-1/DSC- 2 （ P 〈 0.01 ） was also observed. CONCLUSION： There is a close relationship between the expression of HNF4a and the severity of colitis as well as the intercellular linking proteins. The low expression of HNF4a in intestine might aggravate the function of intestinal mucosal barrier, thus promoting the development of UC.