Jörres A, Gahl G M, Ludat K, Frei U, Passlick-Deetjen J
Abteilung für Innere Medizin mit Schwerpunkt Nephrologie und Internistische Intensivmedizin, Virchow-Klinikum der Humboldt-Universität zu Berlin, Germany.
Nephrol Dial Transplant. 1997 Mar;12(3):543-9. doi: 10.1093/ndt/12.3.543.
Conventional lactate-buffered peritoneal dialysis fluids containing glucose as the osmotic agent have been shown to compromise important peritoneal host defence functions. The current study employed an in vitro model using activated peripheral blood mononuclear leukocytes (PBMC) for the preclinical biocompatibility assessment of a novel bicarbonate-buffered peritoneal dialysis fluid containing 1.0% amino acids as the osmotic agent.
PBMC (5 x 10(6)/ml) were pre-exposed (10-30 mm, 37 degrees C) to bicarbonate-buffered 1% amino-acid solution, bicarbonate- or lactate-buffered 1.5% glucose fluid, or control medium (RPMI). The cells were then washed and stimulated for 2 h at 37 degrees C in RPMI containing 100 ng/ml E.coli endotoxin from strain O55:B5. The cytokines IL-6 and TNF alpha in cell supernatants were assessed using specific enzyme immunoassays, cytokine mRNA expression by reverse transcription polymerase chain reaction.
Short, i.e. 10 min, exposure to conventional, lactate-buffered glucose fluid resulted in a significant and time-dependent inhibition of cytokine release and mRNA expression by activated PBMC, whereas the cytokine response was improved even following prolonged (up to 2 h) exposure to bicarbonate-buffered 1% amino-acid solution or bicarbonate-buffered 1.5% glucose fluid.
Our results suggest that very short, i.e. potentially clinically relevant, exposure to conventional dialysis fluid impairs the cytokine response by activated leukocytes. In this respect, the use of bicarbonate-buffered solutions containing 1.0% amino acids or 1.5% glucose may result in improved biocompatibility properties.
含有葡萄糖作为渗透剂的传统乳酸缓冲腹膜透析液已被证明会损害重要的腹膜宿主防御功能。本研究采用体外模型,使用活化的外周血单个核白细胞(PBMC)对一种新型的含有1.0%氨基酸作为渗透剂的碳酸氢盐缓冲腹膜透析液进行临床前生物相容性评估。
将PBMC(5×10⁶/ml)预先暴露(10 - 30分钟,37℃)于碳酸氢盐缓冲的1%氨基酸溶液、碳酸氢盐或乳酸缓冲的1.5%葡萄糖液或对照培养基(RPMI)中。然后洗涤细胞,并在含有100 ng/ml来自O55:B5菌株的大肠杆菌内毒素的RPMI中于37℃刺激2小时。使用特异性酶免疫测定法评估细胞上清液中的细胞因子IL - 6和TNFα,通过逆转录聚合酶链反应评估细胞因子mRNA表达。
短时间(即10分钟)暴露于传统的乳酸缓冲葡萄糖液会导致活化的PBMC释放细胞因子和mRNA表达受到显著且时间依赖性的抑制,而即使长时间(长达2小时)暴露于碳酸氢盐缓冲的1%氨基酸溶液或碳酸氢盐缓冲的1.5%葡萄糖液后,细胞因子反应仍得到改善。
我们的结果表明,非常短时间(即可能具有临床相关性)暴露于传统透析液会损害活化白细胞的细胞因子反应。在这方面,使用含有1.0%氨基酸或1.5%葡萄糖的碳酸氢盐缓冲溶液可能会改善生物相容性。