Willy Kevin, Hulko Michael, Storr Markus, Speidel Rose, Gauss Julia, Schindler Ralf, Zickler Daniel
Nephrology and Intensive Care Medicine, Charite Universitatsmedizin Berlin, Berlin, Germany.
Artif Organs. 2017 Sep;41(9):803-809. doi: 10.1111/aor.12884. Epub 2017 May 19.
Recently developed high-flux (HF) dialysis membranes with extended permeability provide better clearance of middle-sized molecules such as interleukins (ILs). Whether this modulation of inflammation influences the procalcific effects of septic plasma on vascular smooth muscle cells (VSMCs) is not known. To assess the effects of high cut-off (HCO) and medium cut-off (MCO) membranes on microinflammation and in vitro vascular calcification we developed a miniature dialysis model. Plasma samples from lipopolysaccharide-spiked blood were dialyzed with HF, HCO, and MCO membranes in an in vitro miniature dialysis model. Afterwards, IL-6 concentrations were determined in dialysate and plasma. Calcifying VSMCs were incubated with dialyzed plasma samples and vascular calcification was assessed. Osteopontin (OPN) and matrix Gla protein (MGP) were measured in VSMC supernatants. IL-6 plasma concentrations were markedly lower with HCO and MCO dialysis. VSMC calcification was significantly lower after incubation with MCO- and HCO-serum compared to HF plasma. MGP and OPN levels in supernatants were significantly lower in the MCO but not in the HCO group compared to HF. In vitro dialysis of cytokine-enriched plasma samples with MCO and HCO membranes reduces IL-6 levels. The induction of vascular calcification by cytokine-enriched plasma is reduced after HCO and MCO dialysis.
最近开发的具有扩展通透性的高通量（HF）透析膜能更好地清除白细胞介素（ILs）等中等大小的分子。这种炎症调节是否会影响脓毒症血浆对血管平滑肌细胞（VSMCs）的促钙化作用尚不清楚。为了评估高截留（HCO）和中等截留（MCO）膜对微炎症和体外血管钙化的影响，我们建立了一个微型透析模型。在体外微型透析模型中，用HF、HCO和MCO膜对来自脂多糖加样血液的血浆样本进行透析。之后，测定透析液和血浆中的IL-6浓度。将发生钙化的VSMCs与透析后的血浆样本一起孵育，并评估血管钙化情况。测定VSMC上清液中的骨桥蛋白（OPN）和基质Gla蛋白（MGP）。HCO和MCO透析后，IL-6血浆浓度显著降低。与HF血浆相比，用MCO和HCO血清孵育后，VSMC钙化明显降低。与HF相比，MCO组上清液中的MGP和OPN水平显著降低，但HCO组没有。用MCO和HCO膜对富含细胞因子的血浆样本进行体外透析可降低IL-6水平。HCO和MCO透析后，富含细胞因子的血浆对血管钙化的诱导作用降低。
