目的研究可溶性酪氨酸激酶2融合蛋白(sTie-2-Fc)对尿毒症腹膜透析大鼠腹膜血管新生、溶质转运和超滤功能的影响。方法32只雄性Wistar大鼠按数字随机法分为假手术组、尿毒症组、尿毒症腹透组和sTie-2-Fe干预组(均n=8)。尿毒症腹透组和sTie-2-Fc干预组大鼠经腹透管每天2次腹腔灌注4.25%葡萄糖透析液(3ml/100g体质量)共4周,sTie-2-Fc干预组大鼠每次灌注时在透析液中加入1μg sTie-2-Fc。各组大鼠处死前行腹膜平衡试验,检测腹膜转运和超滤功能,取大网膜标本行抗CD31免疫组化染色并计血管数。结果与假手术组大鼠相比,尿毒症组大鼠的2h腹透液和血肌酐比值(D/Pcr)增高(0.78±0.05比0.70±0.09,P=0.028),腹透液2h与0h葡萄糖比值(D/D0)降低(0.69±0.05比0.76±0.07,P=0.033),腹膜超滤量(UF,ml)减少(2.29±0.50比4.58±1.64,P=0.005),腹膜血管数量增加[(5.8±3.0)/HP比(1.6±0.5)/HP,P〈0.01]。尿毒症腹透组大鼠的溶质转运较尿毒症组大鼠进一步增高(D/Pcr:0.89±0.05比0.78±0.05,P〈0.01;D/D0:0.47±0.09比0.69±0.05,P〈0.01),UF(ml)减少(0.40±0.59比2.29±0.50,P=0.005),腹膜血管数量增多[(16.7±1.2)/HP比(5.8±3.0)/HP,P〈0.01]。干预组大鼠使用sTie-2-Fc后,UF(ml)较尿毒症腹透组大鼠显著增加(1.56±0.48比0.40±0.59,P=0.014),腹膜血管数量显著减少[(9.2±1.2)/HP比(16.7±1.2)/HP,P〈0.01],但两组大鼠的D/Pcr和D/D0差异均无统计学意义。结论sTie-2-Fe使尿毒症腹透大鼠腹膜血管新生减少,超滤增加,有利于保护腹膜结构和功能,可能是防治腹透后腹膜结构和功能改变的另一靶点。
Objective To explore the effect of soluble tyrosine kinase 2 fusion protein (sTie-2-Fc) on peritoneal angiogenesis, solute transport and ultrafihration capacity in uremic rats undergoing peritoneal dialysis (PD). Methods Thirty-two male Wistar rats were randomly divided into sham-operation group, uremic group, uremic PD group, and sTie-2-Fc group (all n=8). Uremic PD group and sTie-2-Fc group received intraperitoneal infusion of 3 ml/100 g of peritoneal dialysis fluid (PDF) containing 4.25% glucose twice daily for 4 weeks. Rats in sTie-2-Fc group were infused with PDF supplemented with Ⅱ μg sTie-2-Fc.