Tzu Chi University, Hualien, Taiwan.
Eur J Clin Invest. 2010 Apr;40(4):301-9. doi: 10.1111/j.1365-2362.2010.02264.x.
Peritoneal fibrosis (PF) is a recognized complication of long-term peritoneal dialysis (PD) and can lead to ultrafiltration failure. The present study was designed to investigate the protective effects of aliskiren on chlorhexidine digluconate-induced PF in rats.
The PF was induced in Sprague-Dawley rats by daily administration of 0.5 mL 0.1% chlorhexidine digluconate in normal saline via PD tube for 1 week. Rats received daily intravenous injections of low-dose aliskiren (1 mg kg(-1)) or high-dose aliskiren (10 mg kg(-1)) for 1 week. After 7 days, conventional 4.25% Dianeal (30 mL) was administered via a PD catheter with a dwell time of 4 h and assessed of peritoneal function. At the end of dialysis, rats were sacrificed and the liver peritoneum was harvested for microscopically and immunohistochemistry.
There was no significant difference in mean arterial pressure and heart rate between groups. After 4 h of PD, the D(4)/P(4) urea level was reduced, the D(4)/D(0) glucose level, serum and dialysate transforming growth factor-beta1 (TGF-beta1) level was increased, the liver peritoneum was markedly thicker, and the expression of TGF-beta1, alpha-smooth muscle actin (alpha-SMA), fibronectin, collagen, and vascular endothelial growth factor (VEGF) were elevated in the PS group compared with the vehicle group. Aliskiren decreased the serum and dialysate TGF-beta1 level, decreased the thickness of the liver peritoneum, and decreased the expression of TGF-beta1, alpha-SMA, fibronectin, collagen, and VEGF-positive cells in liver peritoneum. Moreover, high-dose aliskiren had better protective effects against PF than low dose in rats.
Aliskiren protected against chlorhexidine digluconate-induced PF in rats by decreasing TGF-beta1 production.
腹膜纤维化（PF）是长期腹膜透析（PD）的一种公认并发症，可导致超滤失败。本研究旨在探讨阿利克仑对氯己定葡萄糖酸盐诱导的大鼠 PF 的保护作用。
通过 PD 管每天给予生理盐水 0.1%氯己定葡萄糖酸盐 0.5 mL，诱导 Sprague-Dawley 大鼠 PF，持续 1 周。大鼠每天静脉注射低剂量阿利克仑（1 mg/kg）或高剂量阿利克仑（10 mg/kg），持续 1 周。7 天后，通过 PD 导管给予常规 4.25% Dianeal（30 mL），驻留时间为 4 h，并评估腹膜功能。透析结束时，处死大鼠，采集肝腹膜进行显微镜和免疫组织化学检查。
各组大鼠的平均动脉压和心率无显著差异。PD 后 4 h，D（4）/P（4）尿素水平降低，D（4）/D（0）葡萄糖水平、血清和透析液转化生长因子-β1（TGF-β1）水平升高，肝腹膜明显增厚，TGF-β1、α-平滑肌肌动蛋白（α-SMA）、纤维连接蛋白、胶原和血管内皮生长因子（VEGF）的表达在 PS 组较对照组升高。阿利克仑降低了血清和透析液 TGF-β1 水平，降低了肝腹膜厚度，并降低了肝腹膜 TGF-β1、α-SMA、纤维连接蛋白、胶原和 VEGF 阳性细胞的表达。此外，高剂量阿利克仑对大鼠 PF 的保护作用优于低剂量。
阿利克仑通过降低 TGF-β1 的产生来预防氯己定葡萄糖酸盐诱导的 PF。
