Breborowicz A, Polubinska A, Moberly J, Ogle K, Martis L, Oreopoulos D
Department of Pathophysiology, Poznan Medical School, Poznan, Poland.
Am J Kidney Dis. 2001 Mar;37(3):594-600. doi: 10.1053/ajkd.2001.22086.
The effect of high-molecular-weight hyaluronan (HA) on peritoneal and systemic inflammation and peritoneal permeability to water and solutes was studied during endotoxin-induced peritonitis in rats. Acute peritonitis was induced by adding lipopolysaccharide (LPS) to the dialysis fluid (Dianeal 3.86; Baxter Healthcare, Ireland, Castlebar). HA was added to the dialysis solution in a concentration of 10 mg/dL. During 4- and 8-hour dwells of the dialysis fluid, we studied the intensity of peritoneal (dialysate) and systemic (blood) inflammation (dialysate cell count and differential, cytokine and HA levels), as well as the transperitoneal transport of solutes and water. In rats, the addition of LPS to the dialysis fluid induced changes in inflammatory reaction and transperitoneal transport similar to those seen in continuous ambulatory peritoneal dialysis patients with peritonitis. During peritonitis, the addition of HA to the dialysis fluid reduced the loss of ultrafiltration, which resulted in a greater peritoneal creatinine clearance during the 8 hours of dwell (29.9 +/- 6.7 mL/8 h in the HA-LPS group versus 19.7 +/- 7.8 mL/8 h in the LPS group; P < 0.05). Dialysate interferon-gamma (INF-gamma) levels during peritonitis were greater in HA-treated animals (536.8 +/- 296.6 pg/mL in the HA-LPS group versus 169.8 +/- 137.8 pg/mL in the LPS group; P < 0.05). Dialysate elastase activity increased during peritonitis (44.4 +/- 9.3 versus 14.2 +/- 4.1 U/mL in peritonitis-free rats); during peritonitis, the increase in dialysate elastase activity was less pronounced in the rats that had HA in the dialysate (27.3 +/- 4.1 U/mL versus the LPS group; P: < 0.01). We conclude that HA added to the dialysis fluid reduces loss of ultrafiltration during peritonitis in rats. In the presence of HA dialysate, INF-gamma levels during peritonitis increased, whereas elastase activity decreased; these changes might improve the peritoneal immune reaction during peritonitis and at the same time prevent peritoneal membrane injury.
在大鼠内毒素诱导的腹膜炎期间,研究了高分子量透明质酸(HA)对腹膜和全身炎症以及腹膜对水和溶质通透性的影响。通过向透析液(Dianeal 3.86;百特医疗保健公司,爱尔兰卡斯尔巴)中添加脂多糖(LPS)诱导急性腹膜炎。将HA以10mg/dL的浓度添加到透析液中。在透析液4小时和8小时的驻留期间,我们研究了腹膜(透析液)和全身(血液)炎症的强度(透析液细胞计数及分类、细胞因子和HA水平),以及溶质和水的跨腹膜转运。在大鼠中,向透析液中添加LPS会引起炎症反应和跨腹膜转运的变化,这与持续性非卧床腹膜透析腹膜炎患者中观察到的变化相似。在腹膜炎期间,向透析液中添加HA可减少超滤损失,这导致在8小时驻留期间腹膜肌酐清除率更高(HA-LPS组为29.9±6.7mL/8小时,而LPS组为19.7±7.8mL/8小时;P<0.05)。在HA处理的动物中,腹膜炎期间透析液干扰素-γ(INF-γ)水平更高(HA-LPS组为536.8±296.6pg/mL,而LPS组为169.8±137.8pg/mL;P<0.05)。腹膜炎期间透析液弹性蛋白酶活性增加(无腹膜炎大鼠为44.4±9.3对14.2±4.1U/mL);在腹膜炎期间,透析液中含有HA的大鼠透析液弹性蛋白酶活性的增加不太明显(27.3±4.1U/mL对LPS组;P:<0.01)。我们得出结论,向透析液中添加HA可减少大鼠腹膜炎期间的超滤损失。在存在HA透析液的情况下,腹膜炎期间INF-γ水平升高,而弹性蛋白酶活性降低;这些变化可能会改善腹膜炎期间的腹膜免疫反应,同时防止腹膜损伤。