Lee Chung-Jen, Subeq Yi-Maun, Lee Ru-Ping, Liou Hung-Hsiang, Hsu Bang-Gee
Department of Nursing, Tzu Chi College of Technology, Hualien, Taiwan.
Cytokine. 2014 Jan;65(1):105-18. doi: 10.1016/j.cyto.2013.10.003. Epub 2013 Nov 6.
Peritoneal fibrosis is a major complication of peritoneal dialysis that can lead to ultrafiltration failure. This study investigates the protective effects of calcitriol on chlorhexidine digluconate-induced peritoneal fibrosis in rats. Peritoneal fibrosis was induced in Sprague-Dawley rats by daily administration of 0.5mL 0.1% chlorhexidine digluconate in normal saline via peritoneal dialysis for 1week. Rats received daily intravenous injections of calcitriol (low-dose, 10ng/kg; or high-dose, 100ng/kg) for 1week. After 7days, conventional 4.25% Dianeal (30mL) was administered via peritoneal dialysis over 4h. Peritoneal solute transport was calculated from the dialysate concentration relative to its concentration in the initial infused dialysis solution (D4/D0 glucose) for glucose, and the dialysate-to-plasma concentration ratio (D4/P4 urea) at 4h for urea. Rats were then sacrificed and the liver peritoneum was harvested for immunohistochemical analysis via microscopy. After dialysis, the D4/P4 Urea level was reduced; increases were observed in the D4/D0 glucose level and the levels of active transforming growth factor-β1 and angiotensin II in serum and dialysate; the liver peritoneum and muscle peritoneum was markedly thickened, and the expression of α-SMA, fibronectin, collagen, vascular endothelial growth factor, angiotensin II, transforming growth factor-β1, and phosphorylated Smad2/3 (P-Smad2/3)-positive cells in the liver peritoneum was elevated in the peritoneal fibrosis group compared with the vehicle group. Calcitriol decreased the serum and dialysate active transforming growth factor-β1 and angiotensin II level, decreased the thickness of the liver peritoneum and muscle peritoneum, and decreased the expression of α-SMA, fibronectin, collagen, vascular endothelial growth factor, angiotensin II, transforming growth factor-β1, and P-Smad2/3-positive cells in liver peritoneum cells. High-dose calcitriol exhibited better protective effects against peritoneal fibrosis than did the lower dose. Calcitriol protected against chlorhexidine digluconate-induced peritoneal fibrosis in rats by decreasing transforming growth factor-β1 and angiotensin II production.
腹膜纤维化是腹膜透析的主要并发症，可导致超滤失败。本研究探讨骨化三醇对葡萄糖酸氯己定诱导的大鼠腹膜纤维化的保护作用。通过每天经腹膜透析给予0.5mL含0.1%葡萄糖酸氯己定的生理盐水，连续1周，诱导Sprague-Dawley大鼠发生腹膜纤维化。大鼠每天静脉注射骨化三醇（低剂量，10ng/kg；或高剂量，100ng/kg），持续1周。7天后，经腹膜透析在4小时内给予常规的4.25% Dianeal（30mL）。根据透析液浓度相对于初始注入透析液中浓度的比值（D4/D0葡萄糖）计算腹膜溶质转运，对于尿素则计算4小时时的透析液与血浆浓度比值（D4/P4尿素）。然后处死大鼠，取肝脏腹膜进行显微镜下免疫组织化学分析。透析后，D4/P4尿素水平降低；D4/D0葡萄糖水平以及血清和透析液中活性转化生长因子-β1和血管紧张素II水平升高；肝脏腹膜和肌肉腹膜明显增厚，与溶剂对照组相比，腹膜纤维化组肝脏腹膜中α-平滑肌肌动蛋白、纤连蛋白、胶原蛋白、血管内皮生长因子、血管紧张素II、转化生长因子-β1和磷酸化Smad2/3（P-Smad2/3）阳性细胞的表达升高。骨化三醇降低了血清和透析液中活性转化生长因子-β1和血管紧张素II水平，减小了肝脏腹膜和肌肉腹膜的厚度，并降低了肝脏腹膜细胞中α-平滑肌肌动蛋白、纤连蛋白、胶原蛋白、血管内皮生长因子、血管紧张素II、转化生长因子-β1和P-Smad2/3阳性细胞的表达。高剂量骨化三醇对腹膜纤维化的保护作用优于低剂量。骨化三醇通过减少转化生长因子-β1和血管紧张素II的产生，对葡萄糖酸氯己定诱导的大鼠腹膜纤维化具有保护作用。
