大鼠结肠上皮二肽载体异常表达的病理学意义  

Pathology feature of abnormal PepT 1 in colon mucosa in rat

作　　者：石斌[1] 李宁[1] 李幼生[1] 刘放南[1] 

机构地区：[1]南京大学医学院临床学院(南京军区南京总医院)解放军普通外科研究所,江苏南京210002

出　　处：《肠外与肠内营养》2007年第2期77-82,共6页Parenteral & Enteral Nutrition

基　　金：国家自然科学基金资助项目(30371392)

摘　　要：目的:探讨结肠上皮异常表达的二肽载体(PepT1)功能及其转运细菌寡肽产物(fMLP)的病理学意义。方法:用肠切除方法诱导大鼠结肠上皮PepT1表达,大鼠小肠横断后吻合作为对照研究。用Western blot及结肠灌注PepT1底物cephalexin的方法,检测结肠PepT1的表达和功能,分别在结肠PepT1高表达组与低表达组,用fMLP结肠灌注结合组织学检查和髓过氧化物酶(MPO)活性测定,研究PepT1表达与结肠炎性损伤的关系。用PepT1的底物(Gly-Gly)竞争性抑制PepT1对fMLP的转运,观察PepT1在结肠损伤过程中的作用。结果:术后2周,肠切除诱导大鼠结肠表达的PepT1水平最高,术后4周下降,仅为2周的25%。其二肽转运功能随着PepT1的减少而下降。10μmol/LfMLP结肠灌注4h,可导致诱导组大鼠术后2周PepT1高表达的结肠上皮损伤,使组织MPO活性明显升高,而不能导致诱导组大鼠术后4周PepT1低表达的结肠上皮损伤。抑制PepT1功能后,10μmo/LfMLP引发的结肠损伤明显减轻。结论:结肠异常表达的PepT1,具有短肽转运功能。结肠上皮PepT1表达上调,使其对细菌产物的敏感性增加。结肠上皮异常表达的PepT1,可以转运细菌产物而导致结肠炎性损伤。Objective ：This study was to investigate the implication of abnormal PepT1 on rat colonic inflammation by transporting fMLP. Methods：Small bowel resection was adopted to upregulate the PepT1 expression in the colon in rats. The inflammatory effects of PepTl-mediated fMLP transport on the bowel resection rat colon were investigated by means of adopting myeloperoxidase （MPO） activity and histological analysis. Gly-Gly was used to block the PepT1 to determine the role of PepT1 in colonic inflammation. Results ： We found a peak of expression of PepT1 at post-operation week 2 with declining levels to 25% at week 4. The ability of adapting rat colon to transport oligopeptide decreased with the colonic PepT1 diminished. 10 μmol/L fMLP perfusion for 4 h in the colon of bowel resection rat at week 2 after the operation resulted in increased MPO activity and mucosal inflammation, but did not result in any measurable changes in these parameters when administered at week 4 following surgery.The inhibition of PepT1 by administering 50 Mm Gly-Gly inhibited both activation of MPO activity and colonic mucosal damage induced by fMLP. Conclusion：The colonic PepT1 induced by bowel resection provide a mechanism for transport of oligopeptide as well as bacterial product fMLP. Abnormal colonic epithelial PepT1 may serve as a potential way to colon mucosa damage in rats.

关 键 词：肠切除 寡肽载体 短肽转运 细菌寡肽产物 结肠损伤 

分 类 号：R574.62[医药卫生—消化系统]