Ciszewicz Maria, Wu George, Tam Paul, Polubinska Alicja, Breborowicz Andrzej
Department of Pathophysiology, Poznan University of Medical Sciences, Poznan, Poland.
Transl Res. 2007 Dec;150(6):337-42. doi: 10.1016/j.trsl.2007.07.002. Epub 2007 Aug 15.
Glucose is commonly used as an osmotic solute in peritoneal dialysis fluids despite vast knowledge about deleterious peritoneal and systemic effects of that solute. N-acetylglucosamine (NAG) is a solute of the comparable size to glucose, with strong anti-inflammatory properties. We compared the chronic in vitro effect of both solutes on phenotype of peritoneal mesothelial cells. Experiments were performed of primary cultures of human peritoneal mesothelial cells, which were cultured over 4 weeks in medium supplemented either with glucose 45 mmol/L (GLU) or with NAG 45 mmol/L (NAG). Generation of reactive oxygen species (ROS) in cells was studied, as well as their ability to proliferate, synthesis of cytokines, fibronectin, and factors regulating peritoneal fibrinolysis. Cells cultured in the presence of glucose 45 mmol/L generated more ROS (+73% vs control, P < 0.01), whereas NAG did not stimulate generation of ROS. GLU caused hypertrophy of mesothelial cells (+53% vs control, P < 0.001) and prolonged their population doubling time (+16% vs control, P < 0.01); NAG did not cause significant changes in these parameters. Healing of mesothelial monolayer after mechanical injury was impaired in GLU treated cells: (-48% vs control, P < 0.001 and -40% vs NAG, P < 0.05). Synthesis of Il-6, vascular endothelial growth factor (VEGF), transforming growth factor beta (TGFbeta), and fibronectin was higher in GLU group as compared with control: + 86%, P < 0.001, +38%, P < 0.05, +51%, P < 0.001, +38%, P < 0.05, respectively. In the presence of NAG, these parameters were comparable with the control group, but at the same time NAG stimulated synthesis of hyaluronan: +116% versus control, P < 0.001 and + 96% versus GLU, P < 0.01. Treatment with GLU resulted in decline of tissue plasminogen activator/plasminogen activator inhibitor-1 (t-PA/PAI-1) ratio by 23% versus control, P < 0.001, whereas NAG increased that parameter by 43%, P < 0.01 versus control. Glucose, contrary to NAG, induces oxidative stress and proinflammatory and profibrotic changes in mesothelial cells. NAG seems to be more biocompatible osmotic solute than glucose.
尽管人们对葡萄糖作为渗透溶质在腹膜透析液中的有害腹膜和全身影响已有广泛了解，但它仍被普遍用作腹膜透析液中的渗透溶质。N-乙酰葡糖胺（NAG）是一种大小与葡萄糖相当的溶质，具有很强的抗炎特性。我们比较了这两种溶质对腹膜间皮细胞表型的慢性体外影响。实验采用人腹膜间皮细胞原代培养物，将其在补充有45 mmol/L葡萄糖（GLU）或45 mmol/L NAG（NAG）的培养基中培养4周以上。研究了细胞中活性氧（ROS）的产生、细胞增殖能力、细胞因子、纤连蛋白的合成以及调节腹膜纤维蛋白溶解的因子。在45 mmol/L葡萄糖存在下培养的细胞产生了更多的ROS（比对照组增加73%，P < 0.01），而NAG并未刺激ROS的产生。GLU导致间皮细胞肥大（比对照组增加53%，P < 0.001）并延长其群体倍增时间（比对照组增加16%，P < 0.01）；NAG在这些参数上未引起显著变化。GLU处理的细胞在机械损伤后的间皮单层愈合受损：（比对照组减少48%，P < 0.001；比NAG组减少40%，P < 0.05）。与对照组相比，GLU组中白细胞介素-6（Il-6）、血管内皮生长因子（VEGF）、转化生长因子β（TGFβ）和纤连蛋白的合成更高：分别增加86%，P < 0.001；增加38%，P < 0.05；增加51%，P < 0.001；增加38%，P < 0.05。在NAG存在下，这些参数与对照组相当，但同时NAG刺激了透明质酸的合成：比对照组增加116%，P < 0.001；比GLU组增加96%，P < 0.01。与对照组相比，GLU处理导致组织纤溶酶原激活物/纤溶酶原激活物抑制剂-1（t-PA/PAI-1）比值下降23%，P < 0.001，而NAG使该参数增加43%，与对照组相比P < 0.01。与NAG相反，葡萄糖可诱导间皮细胞产生氧化应激以及促炎和促纤维化变化。NAG似乎是一种比葡萄糖生物相容性更好的渗透溶质。
