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首页> 外文期刊>Cytokine >Calcitriol decreases TGF-β1 and angiotensin II production and protects against chlorhexide digluconate-induced liver peritoneal fibrosis in rats
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Calcitriol decreases TGF-β1 and angiotensin II production and protects against chlorhexide digluconate-induced liver peritoneal fibrosis in rats

机译:骨化三醇可降低TGF-β1和血管紧张素II的产生,并防止氯葡萄糖酸二葡萄糖酸酯诱导的大鼠肝腹膜纤维化

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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.
机译:腹膜纤维化是腹膜透析的主要并发症,可导致超滤失败。这项研究调查了骨化三醇对氯己定二葡萄糖酸酯诱导的大鼠腹膜纤维化的保护作用。在Sprague-Dawley大鼠中,通过腹膜透析每天给予0.5mL 0.1%生理盐水中的0.1%洗必泰二葡萄糖酸盐,进行腹膜透析,诱导腹膜纤维化。大鼠每天接受钙三醇(小剂量10ng / kg;大剂量100ng / kg)静脉注射1周。 7天后,在4小时内通过腹膜透析施用常规的4.25%Dianeal(30mL)。根据透析液浓度相对于透析液在初始输注透析液中的浓度(D4 / D0葡萄糖)来计算腹膜溶质转运量,而尿素在4h时的透析液与血浆的浓度比(D4 / P4尿素)计算得出。然后处死大鼠,并收集肝腹膜用于通过显微镜检查进行免疫组织化学分析。透析后,D4 / P4尿素水平降低;血清和透析液中的D4 / D0葡萄糖水平以及活性转化生长因子-β1和血管紧张素II水平升高;肝腹膜和肌肉腹膜明显增厚,α-SMA,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)阳性表达与溶媒组相比,腹膜纤维化组的肝腹膜细胞升高。骨化三醇降低血清和透析液活性转化生长因子-β1和血管紧张素II的水平,降低肝腹膜和肌肉腹膜的厚度,并降低α-SMA,纤连蛋白,胶原蛋白,血管内皮生长因子,血管紧张素II,转化的表达肝腹膜细胞中的生长因子-β1和P-Smad2 / 3阳性细胞。高剂量骨化三醇比低剂量骨化石对腹膜纤维化具有更好的保护作用。骨化三醇通过减少转化生长因子-β1和血管紧张素II的产生来保护大鼠免受葡萄糖酸洗必泰诱导的腹膜纤维化的影响。

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