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脂质体支持的腹膜透析清除蛋白结合型尿毒症毒素。

Removal of Protein-Bound Uremic Toxins by Liposome-Supported Peritoneal Dialysis.

机构信息

Division of Nephrology and Unit of Critical Nephrology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, China.

Division of Nephrology and Unit of Critical Nephrology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, China

出版信息

Perit Dial Int. 2019 Nov-Dec;39(6):509-518. doi: 10.3747/pdi.2018.00229.

Abstract

Protein-bound uremic toxins (PBUTs) are poorly cleared by peritoneal dialysis (PD). This study aimed to enhance PBUT removal in PD by adding a binder to the peritoneal dialysate and to evaluate the feasibility and efficacy of liposome-supported PD (LSPD) to increase the removal of PBUTs compared with albumin PD.Removal of p-cresyl sulfate (PCS), indoxyl sulfate (IS), and indole-3-acetic acid (3-IAA) was first evaluated in an PD model using artificial plasma preloaded with test solutes. Male Sprague-Dawley rats ( = 24) were then subjected to 5/6 nephrectomy and fed for 16 weeks to establish end-stage renal failure, after which they were treated with either conventional glucose-based PD, albumin-based PD, or liposome-based PD. Removal of PBUTs and small water-soluble solutes was determined during a 6-hour PD dwell.In vitro experiments showed that adding albumin as a toxin binder to the dialysate markedly increased the removal of PCS, IS, and 3-IAA compared with the control. The uptake capacity of liposomes was comparable with that of albumin for PCS and 3-IAA, though slightly inferior for IS. PD in uremic rats demonstrated that LSPD resulted in higher intraperitoneal concentrations and more total mass removal for PBUTs than the conventional glucose-based PD, which was comparable with albumin PD.Supplementing conventional glucose-based PD solutions with a binder could efficiently increase the removal of PBUTs. This preliminary study suggested that LSPD may be a promising alternative to albumin PD for increasing PBUT removal in the development of next-generation PD solutions for PD patients.

摘要

蛋白质结合型尿毒症毒素 (PBUTs) 经腹膜透析 (PD) 清除效果不佳。本研究旨在通过向腹膜透析液中添加结合剂来增强 PD 对 PBUT 的清除作用,并评估载脂蛋白 PD (LSPD) 与白蛋白 PD 相比增加 PBUT 清除的可行性和疗效。

首先,在使用人工血浆预加载测试溶质的 PD 模型中评估对 p- 对甲苯磺酸 (PCS)、吲哚硫酸 (IS) 和吲哚-3- 乙酸 (3-IAA) 的去除效果。然后,雄性 Sprague-Dawley 大鼠 ( = 24) 接受 5/6 肾切除术并饲养 16 周以建立终末期肾衰竭,之后用常规葡萄糖 PD、白蛋白 PD 或载脂蛋白 PD 进行治疗。在 6 小时 PD 停留期间测定 PBUT 和小水溶性溶质的清除率。

体外实验表明,与对照组相比,向透析液中添加白蛋白作为毒素结合剂可显著增加 PCS、IS 和 3-IAA 的清除率。与 IS 相比,载脂蛋白对 PCS 和 3-IAA 的摄取能力与白蛋白相当。在尿毒症大鼠的 PD 中,LSPD 导致 PBUT 的腹腔内浓度更高,总去除量高于常规葡萄糖 PD,与白蛋白 PD 相当。

用结合剂补充常规葡萄糖 PD 溶液可有效增加 PBUT 的清除率。这项初步研究表明,LSPD 可能是白蛋白 PD 的一种有前途的替代方法,可用于增加 PBUT 清除率,以开发用于 PD 患者的下一代 PD 溶液。

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