GLP-2对实验性梗阻性黄疸小肠上皮细胞紧密连接的调控
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陈振勇

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Efect of glucagon-like peptide-2 on modulation of intestinal epithelium tight junction in rats with obstructive jaundice
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    摘要:

    目的:探讨类高血糖素多肽-2(GLP-2)对实验性梗阻性黄疸小肠上皮细胞紧密连接的调控。
    方法:建立梗阻性黄疸大鼠模型,造模后10d随机分组,每组10只。黄疸组皮下注射0.01 mmol/LPBS 0.5 mL,实验甲组腹腔注射250 g/(kg·d),实验乙组腹腔注射125g/(kg·d)的GLP-2溶液0.5 mL,每天2次,连续7 d后处死。另设正常对照组,用免疫组化及Western blots检测末端回肠黏膜紧密连接蛋白ZO-1,Occludin及Claudin-1, Claudin-4的分布和表达,并用图像分析系统对Western blots图像进行定量分析。
    结果:正常情况下ZO-1,Occludin和Claudin-1染色强阳性率分别为70.0%,80.0%和70.0%。梗阻性黄疸时ZO-1和Occludin分布不均,染色变淡,线条模糊。补充外源性GLP-2后,实验甲组的ZO-1,Occludin和Claudin-1染色有所恢复,且强阳性表达率分别从黄疸组的20.0%,30.0%和20.0%升至实验甲组的80.0%,90.0%和80.0% (均P<0.05);Claudin-4表达和分布变化不明显。实验乙组对紧密连接蛋白无影响。Western blots图像定量分析得到相同的结果。
    结论:梗阻性黄疸时,补充GLP-2可影响小肠黏膜上皮紧密连接蛋白的分布和表达;提示GLP-2能恢复和维持小肠黏膜上皮屏障的完整性。

    Abstract:

    Abstract:Objective:To study the effects of GLP-2 on modulation of intestinal mucosa epithelium tight junction in obstructive jaundice rats.
    Methods :The obstructive jaundice model of rats was set up. At 10 days after operation, the rats were randomly divided into 4 groups: normal group, jaundice group,experiment group A and B. Each group consisted of 10 animals.The animals of jaundice group had subcutaneous injection of 0.5ml 0.01mmol/LPBS,experiment group A had intraperitoneal injecton of 0.5 mL 250 g/(kg.d) GLP-2; experiment group B intraperitoneal injectied 0.5ml 125g/ (kg.d)GLP-2, b.i.d×7. Immunohistochemistry and Western-blot were used to examine the distribution and expression of tight junction proteins ZO-1, occludin and Claudin-1,-4 in the terminal ileum mucosa. Image analytical system and statistics software were used to analyze the results quantitately.
    Results:In normal group, the strong positive expression ratios of ZO-1,occludin and claudin-1 were 70.0%,80.0% and 70.0% respectively. In jaundice group, ZO-1 and Occludin staining appeared discontinuous and vague. ZO-1, occludin and claudin-1 staining recovered somewhat after exogenously supplied GLP-2 in experiment group A. The strong positive expression ratios were obviously higher in experiment group A than those in the jaundice group (20.0% vs 80.0%,30.0% vs90.0%,20.0% vs 80.0%,all P<0.05). The distribution and expression of Claudin-4 altered insignificantly. There were no noticeable changes in the expression and quantity of tight junction proteins in experiment group B. The same outcomes were obtained by quantitative analysing Western blot images.
    Conclusions:Exogenous supplemented GLP-2 in obstructive jaundice can influence the expression and distribution of the tight junction proteins ZO-1, occludin,Claudin-1 of intestinal mucosa. This suggests that GLP-2 could recover and maintain the integrity of intestinal mucosa epithelium barrier.

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陈振勇, 冯贤松, 杨鹏, 周有生. GLP-2对实验性梗阻性黄疸小肠上皮细胞紧密连接的调控[J].中国普通外科杂志,2008,17(8):7-763.
DOI:10.7659/j. issn.1005-6947.2008.08.007

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  • 在线发布日期: 2008-08-25