Ciszewicz Marta, Polubinska Alicja, Antoniewicz Artur, Suminska-Jasinska Katarzyna, Breborowicz Andrzej
Department of Pathophysiology, Poznan University of Medical Sciences, Poznan, Poland.
Transl Res. 2009 Mar;153(3):118-23. doi: 10.1016/j.trsl.2008.12.007. Epub 2009 Jan 23.
Sulodexide is a mixture of heparin and dermatan sulfate with antithrombotic and profibrynolytic activity. Individual reports suggest the anti-inflammatory action of sulodexin. The goal of this study was to evaluate the effect of sulodexide on the release of the inflammatory mediators from endothelium in normal conditions and in cells chronically exposed to glucose. The experiments were performed on in vitro cultured human umbilical endothelial cells kept for 7 days in standard medium or in the same medium but supplemented with glucose 30 mmol/L. Sulodexide was added to the culture medium in concentrations of 0.125 lipase releasing unit (LRU)/mL, 0.25 LRU/mL, and 0.5 LRU/mL Spontaneous generation of oxygen-derived free radicals and the release of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) from the studied cells was evaluated. Additionally, the healing of the injured mesothelium was studied in the presence of sulodexide and glucose. Sulodexide caused the inhibition of the intracellular generation of free radicals in a dose-dependent manner (maximally by 32%, P < 0.01), as well as the inhibition of MCP-1 (maximally by 60%, P < 0.001) and IL-6 (maximally by 69%, P < 0.01). Cells cultured in a medium with glucose 30 mmol/L generated more free radicals (+20%, P < 0.05) and released more MCP-1 (+113%, P < 0.001) and IL-6 (+26%, P < 0.05). Cell monolayers treated with glucose had a decreased ability to heal after mechanical injury (-28%, P < 0.001). All these glucose effects were reversed when cells were exposed to sulodexide simultaneously. The results of our study demonstrate a significant anti-inflammatory action of sulodexide in the endothelial cells and a protective effect of that drug against glucose cytotoxicity.
舒洛地希是一种具有抗血栓形成和促纤溶活性的肝素与硫酸皮肤素的混合物。个别报告提示舒洛地新具有抗炎作用。本研究的目的是评估舒洛地希在正常条件下以及在长期暴露于葡萄糖的细胞中对内皮细胞炎症介质释放的影响。实验在体外培养的人脐静脉内皮细胞上进行，这些细胞在标准培养基中培养7天，或在相同培养基但添加30 mmol/L葡萄糖的条件下培养。将舒洛地希以0.125脂肪酶释放单位（LRU）/mL、0.25 LRU/mL和0.5 LRU/mL的浓度添加到培养基中。评估所研究细胞中氧衍生自由基的自发产生以及单核细胞趋化蛋白-1（MCP-1）和白细胞介素-6（IL-6）的释放。此外，在有舒洛地希和葡萄糖存在的情况下研究受损间皮的愈合情况。舒洛地希以剂量依赖方式抑制细胞内自由基的产生（最大抑制32%，P<0.01），以及抑制MCP-1（最大抑制60%，P<0.001）和IL-6（最大抑制69%，P<0.01）。在含有30 mmol/L葡萄糖的培养基中培养的细胞产生更多自由基（增加20%，P<0.05），释放更多MCP-1（增加113%） ，P<0.001）和IL-6（增加26%，P<0.05）。用葡萄糖处理的细胞单层在机械损伤后的愈合能力下降（降低28%，P<0.001）。当细胞同时暴露于舒洛地希时，所有这些葡萄糖的作用均被逆转。我们的研究结果表明舒洛地希在内皮细胞中具有显著的抗炎作用，并且该药物对葡萄糖细胞毒性具有保护作用。
