可溶性酪氨酸激酶2融合蛋白对尿毒症腹膜透析大鼠腹膜形态和功能的影响

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-Fc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（3 ml/100 g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1 μg 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2 h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2 h与0 h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-Fc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。

Soluble tyrosine kinase 2 fusion protein ameliorates peritoneal morphologic and functional changes in uremic peritoneal dialysis rats

Objective To explore the effect of soluble tyrosine kinase 2 fusion protein (sTie-2-Fc) on peritoneal angiogenesis, solute transport and ultrafi]tration 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 1 μg sTie-2-Fc. Before the rats were sacrificed, a peritoneal equilibration test (PET) was performed to evaluate the peritoneal solute transport and ultrafiltration capacity, and omenta was obtained for anti-CD31 immunohistochemical staining to determine the vessel density. Results Compared to their counterparts in sham-operation group,rats in uremic group had higher 2 h-dialysate to plasma creatinine concentration ratio (D/Pcr, 0.78±0.05 vs 0.70±0.09, P=0.028), lower 2 h to initial dialysate glucose concentration ratio (D/D0, 0.69±0.05 vs 0.76±0.07, P=0.033), decreased peritoneal ultrafiltration [UF, (2.29±0.50) ml vs (4.58±1.64) ml, P=0.005], and increased omental vessel density [(5.8±3.0)/HP vs (1.6±0.5)/HP, P＜0.01]. When compared to uremic group, rats in uremic PD group showed higher D/Pcr (0.89±0.05 vs 0.78±0.05, P=0.001), lower D/D0 (0.47±0.09 vs 0.69±0.05, P＜0.01), decreased UF [(0.40±0.59) ml vs (2.29±0.50) mi, P=0.005] and more omental vessels [(16.7±1.2)/HP vs (5.8±3.0)/HP, P＜0.01]. Improved peritoneal UF [(1.56±0.48) ml vs (0.40±0.59) mi, P=0.014] and decreased omental vessels [(9.2± 1.2)/HP vs (16.7 ± 1.2)/HP, P＜0.01] were observed in rats treated with sTie-2-Fc compared with those in uremic PD group, however, the differences of D/Pcr (0.87±0.06 vs 0.89±0.05, P=0.122) and D/D0 (0.60±0.11 vs 0.47±0.09, P=0.06) between these two groups did not reach statistical significance. Conclusion sTie-2-Fc preserves peritoneal ultrafiltration capacity and ameliorates peritoneal angiogenesis caused by uremia and exposure to bioincompatibal PDF.