Aliskiren ameliorates chlorhexidine digluconate-induced peritoneal fibrosis in rats.

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION(2010)

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摘要
P>Background 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. Materials and methods The PF was induced in Sprague-Dawley rats by daily administration of 0 center dot 5 mL 0 center dot 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 center dot 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. Results 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-beta 1 (TGF-beta 1) level was increased, the liver peritoneum was markedly thicker, and the expression of TGF-beta 1, 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-beta 1 level, decreased the thickness of the liver peritoneum, and decreased the expression of TGF-beta 1, 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. Conclusions Aliskiren protected against chlorhexidine digluconate-induced PF in rats by decreasing TGF-beta 1 production.
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Aliskiren,chlorhexidine digluconate,peritoneal fibrosis
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