聚乙二醇修饰猪胰高血糖素样肽-2对试验性结肠炎小鼠肠道紧密连接蛋白和炎性因子基因表达的影响

Effects of Polyethylene Glycosylation Porcine Glucagon-Like Peptide-2 on Gene Expression of Tight Junction Proteins and Inflammatory Cytokines in a Murine Model of Experimental Colitis

本试验旨在研究聚乙二醇(PEG)修饰猪胰高血糖素样肽-2(pGLP-2)对结肠炎小鼠肠道紧密连接蛋白和炎性因子基因表达的影响。试验选取24只BALB/C小鼠,随机分为4组,葡聚糖硫酸钠(DSS)组小鼠饮用3%DSS建立小鼠结肠炎模型,DSS+pGLP-2组和DSS+PEGpGLP-2组饮用3%DSS且在试验第8天腹腔分别注射pGLP-2和PEG-pGLP-2,饮水组小鼠正常饮水。试验期10 d。结果表明:与饮水组相比,DSS组小鼠结肠紧密连接闭锁小带基因(ZO-1)的mRNA相对表达量极显著降低(P<0.01);与DSS组相比,注射pGLP-2对ZO-1的mRNA相对表达量没有改善(P>0.05),而注射PEG-pGLP-2可极显著增加ZO-1的mRNA相对表达量(P<0.01)。与饮水组相比,DSS组小鼠结肠白细胞介素-6(IL-6)、白细胞介素-10(IL-10)和干扰素-γ基因(INF-γ)的mRNA相对表达量极显著增加(P<0.01);与DSS组相比,注射pGLP-2和PEG-pGLP-2可极显著降低IL-6、IL-10和IFN-γ的mRNA相对表达量(P<0.01)。结果提示,PEG-pGLP-2通过增加肠道紧密连接蛋白的表达、降低结肠炎小鼠炎性细胞因子的表达抑制其炎性病变,且作用效果优于pGLP-2。

This study aimed to evaluate the effects of polyethylene glycosylation （PEGylation） porcine gluca- gon-like peptide-2 （pGLP-2） （PEGylation pGLP-2） on gene expression of tight junction proteins and inflam- matory cytokines in a murine model of experimental colitis. Twenty-four BALB/C mice were randomly as- signed into four groups： dextran sulfate sodium （DSS, mice colitis model by drinking 3% DSS）, DSS＋pGLP- 2 （3% DSS by drinking＋pGLP-2 by intraperitoneal injection on the 8th day）, DSS＋PEG-pGLP-2 （3% DSS by drinking＋PEG-pGLP-2 by intraperitoneal injection on the 8th day） and water groups for 10 days. The re- sults showed as follows： compared with the water group, DSS significantly decreased the mRNA expression level of zonula occludens-1 （ZO-1） in colon （P〈0.01）. Specifically, PEG-pGLP-2, nor pGLP-2 injection （P〉0.05） significantly increased the ZO-1 mRNA expression level compared with the DSS group （P〈0.01）. Compared with the water group, DSS group significantly increased the mRNA expression levels of interleukin- 6 （IL-6）, interleukin-10 （IL-10） and interferon-γ （INF-γ） in colon （P〈0.01）. And PEG-pGLP-2 and pGLP-2 injection significantly decreased the IL-6, IL-IO and INF-γ mRNA expression levels compared with the DSS group （ P〈0.01 ）. These results show that PEG-pGLP-2 reduce the severity of colonic injury in murine co- litis by increasing the expression of the tight junction proteins and reducing the expression of inflammatory cyto- kines. The therapy of PEG-pGLP-2 is better than that of pGLP-2.