study on the changes in peritoneal ultrafiltration in peritoneal dialysis in relation to the regulation of the gene expression of peritoneal aquaporins

最近，我们发现腹膜水通道蛋白(AQP1和AQ4)的基因表达在持续腹膜透析(PD)初期一过性增强。为了研究水通道蛋白在长期CAPD患者超滤丢失中的作用，我们设计了2个月的长期实验PD。在腹膜腔内放置小导管，用于交换透析液和取样。给予生理盐水(对照组)或含葡萄糖人用透析液(1.35%或4.0%)，每日2次。每日监测的出水量(超滤量)在初始阶段增加，然后固定，如上一次实验所观察到的那样。腹膜组织学改变不明显，如间皮脱落或间皮下纤维化。术后5周流出量逐渐减少，但未达到统计学意义。8…后腹膜水通道蛋白1和4的基因表达RT-PCR结合酶联免疫吸附试验分析显示，透析周数较透析前明显减少(无统计学意义)。原位杂交结果显示，透析8周后毛细血管内皮细胞内信号聚集不明显，但差异不显著。要证实水通道蛋白在长期接受CAPD治疗的患者超滤失败中的作用，还需要进一步研究。接下来，为了研究机械牵张在AQP基因表达诱导中的作用，我们设计了体内和体外实验。体内实验采用带球囊的小导管置入大鼠腹腔扩张腹膜，无需透析。在体外实验中，将机械划伤腹膜获得的间皮细胞培养在橡胶板上，然后进行30%的统计拉伸或60 Hz的循环拉伸。体内腹膜扩张后第3天AQP基因表达一过性增强，与实验透析时相似。但体外实验无显著差异，提示腹膜扩张的间接作用可能参与了AQP基因表达的一过性增强。临床上，CAPD患者在停止PD治疗几周后，有时会意外地从超滤失败中恢复过来。腹膜扩张诱导的AQP基因表达可能参与了这一现象。较少

Recently, we have found that gene expression of peritoneal aquaporins (AQP1 and 4) was enhanced transitorily at the initial phase of continuous peritoneal dialysis (PD) in rats. To study the involvement of AQP in the ulltrafiltration loss occurred in long term CAPD patients, we designed long term experimental PD for 2 months in rats. Small catheter was settled in the abdominal cavity for exchanging dialysate and sampling.. Physiological saline (for control) or glucose-containing human-use dialysate(1.35% or 4.0%) were administered and exchanged twice a day. Daily monitored effluent volume (ultrafiltration volume) was increased in the initial phase and subsequently fixed, as observed in the previous experiment. Histological changes in the peritoneum such as mesothelium detachment or submesothelial fibrosis were not obvious. The effluent volume was gradually decreased after 5 weeks although we failed to obtain the statistical significance. Gene expression of peritoneal AQP1 and 4 after 8 … More weeks dialysis was inclined to be decreased comparing to that before dialysis (statistically insignificant) studied by RT-PCR combined with ELISA analysis. In situ hybridization study revealed that the signal accumulation in the capillary endothelium was less obvious after 8 weeks dialysis,but it was not significant. To confirm the involvement of AQP in the ultrafiltration failure in patients with long-term CAPD therapy, further study must be required. Next, to study the involvement of mechanical stretch in the induction of AQP gene expression, we designed in vivo and in vitro experiments. For in vivo experiment, small catheter with balloon was settled into the rats abdominal cavity to expand the peritoneum without dialysis. For in vitro experiment, mesothelial cells obtained by mechanical scratch of the peritoneum were cultured on the rubber plate, for subsequent application to 30% statistic stretch or 60 Hz cycled stretch. Peritoneum expansion in vivo generated transient enhancement of AQP gene expression at the day 3, which was similar pattern to that in experimental dialysis. However, there was no significant difference in in vitro experiement, suggesting that indirect effect of peritoneal expansion might be involved in the transient enhancement of AQP gene expression. Clinically, unexpected recovery from ultrafiltration failure in CAPD patients is sometimes experienced after few weeks discontinuation of PD. The peritoneal expansion induced AQP gene expression may be involved in the phenomenone. Less