尿素转运蛋白(UT)介导尿素跨膜转运，在尿浓缩和调节氮平衡中起重要作用。胃肠道粘膜上皮细胞有UT表达，当肾脏功能受损时，尿液中的尿素排泄减少，血液中尿素浓度增加，尿素向肠腔内分泌增加，有助于减轻体内氮负荷。本课题通过人工诱导UT-B基因突变，筛选可提高尿素转运效率的UT-B突变基因(UT-Bm)，并构建带有突变UT-Bm的重组腺病毒载体,在体外转染结肠上皮细胞株Caco-2,采用RT-PCR、Western blot检测UT-Bm mRNA和蛋白的表达，同位素标记法检测Caco-2细胞尿素转运功能的改变；将带有UT-Bm基因的重组腺病毒注入5/6肾切除的大鼠结肠，检测UT-Bm mRNA和蛋白在肠组织的表达及肠道尿素排泄量、大鼠血肌酐、尿素氮浓度改变，明确带有UT-Bm的肠上皮细胞是否能更有效地清除尿毒症毒素，为慢性肾衰竭患者寻找新的治疗途。

Urea transporter(UT), expressed on gastrointestinal epithelial cells and functioning as the mediator of urea transmembrane transportation, plays an important role in urine concentration and regulation of nitrogen balance. The impairment of renal function will reduce the urine excretion of urea and then the concentration of urea will elevate in the blood. The increase of intestinal excretion of urea through UT can help relieve the overload of urea in the body. Accordingly, we aim to firstly construct the recombinant adenovirus vector expressing artificial induced mutational UT-B(UT-Bm) with the ability of increasing urea transportation, then transfect the human intestinal epithelial cell line Caco-2. The mRNA and protein expression of UT-Bm in Caco-2 will be determined by RT-PCR and Western blot, and the urea transportation ability of Caco-2 after transfection will be tested through isotope-labeling method. In the in vivo study, through the injection of recombinant adenovirus vector with UT-Bm into intestine of 5/6 nephrectomized rat, alterations of mRNA and protein expression of UT-Bm in intestine epithelial cell, the intestinal urea excretion level, serum creatinine and BUN will be tested to determine whether intestine epithelial cell with UT-Bm can increase urea excretion. This innovative study aims to find a new treatment for patients with chronic kidney disease.