Effect of Different Buffers on the Biocompatibility of Capd Solutions
Effect of Different Buffers on the Biocompatibility of Capd Solutions
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不同缓冲液对 Capd 溶液生物相容性的影响
DOI：
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发表时间：
1996
影响因子：
2.8
通讯作者：
H. Schambye
中科院分区：
文献类型：
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作者：
H. Schambye
用于持续性非卧床腹膜透析（CAPO）的市售溶液影响腹膜腔中细胞的活力和功能。溶液的低生物相容性可能是由低pH值、高渗透压、高葡萄糖含量以及缺乏钾、谷氨酰胺和正常细胞功能所必需的其他组分引起的。所用缓冲液的性质对溶液的细胞毒性也很重要。乳酸盐是最常用的缓冲液，已显示可抑制对腹膜防御系统重要的细胞功能，包括吞噬作用、细菌杀伤和细胞因子分泌。一般认为，乳酸的细胞毒性是由细胞内pH降低和氧化还原电位改变导致的代谢受损引起的。然而，乳酸盐的细胞毒性高度依赖于溶液的pH值，这表明乳酸盐通过细胞膜的被动或主动扩散决定了乳酸盐的作用。大力提倡将Biclonal作为替代缓冲液，因为它是血浆中最重要的天然缓冲液，并且能够使溶液的pH值达到约7.4。然而，由于碳酸钙（CaCO 3）的沉降和有毒葡萄糖代谢物的产生，难以制备和储存基于碳酸氢盐的溶液。此外，研究表明，即使是碳酸氢盐基溶液在生物相容性方面也不是最佳的，这可能是由于二氧化碳（CO2）流入引起的矛盾的细胞内酸化。最近，已经检查了其他缓冲剂如丙酮酸盐和组氨酸的效果。特别是丙酮酸是一种有前途的新的缓冲剂候选者。基于乳酸盐的常规CAPD溶液已被证明会损害对腹膜宿主防御重要的多种细胞功能。除了高渗透压、高葡萄糖浓度、缺乏钾、谷氨酰胺和其他因素的影响外，这似乎是由于低pH和高乳酸盐浓度的组合。据推测，乳酸携带质子穿过膜，这导致细胞内酸化和细胞内乳酸浓度增加，这两者都可能损害细胞代谢和功能。基于碳酸氢盐的溶液比基于乳酸盐的溶液毒性更小-主要归因于较高的pH值。然而，我们小组进行的实验表明，碳酸氢盐浓度过高也可能影响细胞功能，并且含有碳酸氢盐和乳酸盐的溶液可能是上级。然而，需要进一步的研究来充分阐明这一问题。丙酮酸盐似乎是一种有前途的新的缓冲剂候选者，在相同的pH值和葡萄糖含量下，其毒性低于乳酸盐溶液。比较丙酮酸盐、乳酸盐和碳酸氢盐溶液的细胞毒性，特别是细胞内酸化，有望揭示这些溶液的毒性特性。
Commercially available solutions for continuous ambulatory peritoneal dialysis (CAPO) affect the viability and function of the cells in the peritoneal cavity. The low biocompatibility of the solutions may be caused by a low pH, hyperosmolality, high glucose content, and lack of potassium, glutamine, and other components essential for normal cellular functions. The nature of the buffer employed is also important for the cytotoxicity of the solutions. Lactate, the most frequently used buffer, has been shown to inhibit cellular functions important for the peritoneal defense system including phagocytosis, bacterial killing, and secretion of cytokines. It is generally believed that the cytotoxicity of lactate is caused by lowering of intracellular pH and impairment of metabolism due to changed redox potentials. However, the cytotoxicity of lactate is highly dependent upon the pH of the solutions, indicating that passive or active diffusion across the cell membrane is determining the effects of lactate. Bicarbonate has been heavily advocated as an alternative buffer because it is the most important naturally occurring buffer in plasma and it enables a pH of approximately 7.4 in the solutions. However, due to sedimentation of calcium carbonate (CaCO3) and production of toxic glucose metabolites it is difficult to prepare and store bicarbonate-based solutions. Moreover, investigations have revealed that even bicarbonate-based solutions are not optimal regarding biocompatibility, presumably due to a paradoxical intracellular acidification caused by influx of carbon dioxide (CO2). More recently, the effect of other buffers such as pyruvate and histidine have been examined. Especially pyruvate is a promising new buffer candidate. Conventional CAPD solutions based on lactate have been shown to impair a wide variety of cell functions important for the peritoneal host defense. Apart from the influence of hyperosmolality, high glucose concentration, lack of potassium, glutamine, and other factors, this seems to be due to the combination of low pH and high lactate concentration. Presumably, lactate carries protons across the membrane, which results in intracellular acidification and increased intracellular lactate concentration, both of which may impair cell metabolism and function. Bicarbonate-based solutions are less toxic than lactate-based solutions -primarily attributable to the higher pH. However, experiments performed by our group have indicated that bicarbonate concentrations that are too high may also affect cell function, and that a solution containing both bicarbonate and lactate may be superior. However, further studies are needed to fully elucidate this problem. Pyruvate seems to be a promising new buffer candidate with lower toxicity than lactate solutions at identical pH and glucose content. Comparison of pyruvate, lactate, and bicarbonate solutions regarding cytotoxicity and especially intracellular acidification will hopefully shed new light on the toxic properties of these solutions.
影响因子：
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作者：
D. Dunn;R. Barke;D. Ewald;R. L. Simmons
通讯作者：
D. Dunn;R. Barke;D. Ewald;R. L. Simmons