中国血液净化

中国血液净化 ›› 2015, Vol. 14 ›› Issue (10): 604-607.doi: 10.3969/j.issn.1671-4091.2015.10.00

• 临床研究 • 上一篇    下一篇

蛋白结合类尿毒症毒素血清游离浓度及蛋白结合率的研究

任真真1,李新伦1,李红霞1,伦立德1,窦桂芳2   

  1. 1.空军总医院肾病科
    2. 军事医学科学院药代动力学实验室
  • 收稿日期:2015-04-14 修回日期:2015-05-23 出版日期:2015-10-12 发布日期:2015-10-12
  • 通讯作者: 伦立德 lunlideldm@163.com E-mail:352996962@qq.com

The study of serum concentrations of free protein binding uremic toxins and their plasma protein binding rate

  • Received:2015-04-14 Revised:2015-05-23 Online:2015-10-12 Published:2015-10-12

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摘要： 目的 测定慢性肾脏病(chronic kidney disease,CKD)患者血清马尿酸(hippuric acid，HA)、硫酸吲哚酚(indoxyl sulfate，IS)、硫酸对甲酚(p-cresyl sulfate，PCS)及3-羧基-4-甲基-5-丙基-2-呋喃丙酸(3-carboxy-4-methyl- 5-propyl-2-furan-propionic acid，CMPF)4 种蛋白结合类毒素的游离浓度及蛋白结合率，了解游离浓度、蛋白结合率与肾功能变化之间的关系。方法将40 例CKD 患者依据肾功能分为CKD3 期组、CKD4 期组、CKD5 期组及维持性血液透析治疗 ( maintenance hemodialysis, MHD) 组，另外选取10 例健康志愿者作为对照组。采用超滤法分离血清游离HA、IS、PCS 及CMPF，应用高效液相色谱-串联质谱(High performance liquid chromatagraphy-Tandem Mass Spectrometry，HPLS-MS/MS)技术测定CKD 患者血清HA、IS、PCS、CMPF 的游离浓度，计算以上4 种物质的蛋白结合率。结果各组HA、IS、PCS 及CMPF 的游离浓度分别为：健康对照组(μg/ml) 2.13(1.36～3.53)、0.11(0.07～017)、0.43(0.14～0.59)、0.26(0.24～0.28)；CKD3 期(μg/ml) 2.88(1.76～5.63)、0.23(0.05～0.48)、0.96(0.56～2.08)、0.30(0.25～0.31)；CKD4 期(μg/ml) 8.78(3.32～17.88)、0.55(0.26～0.91)、1.21(0.53～4.33)、0.32(0.29～0.50)；CKD5 期(μg/ml) 24.05(3.56～62.55)、3.16(0.96～8.10)、5.42(0.62～12.83)、0.28(0.25～0.35)；MHD 组(μg/ml) 101.95(23.23～125.25)、6.29 (2.06～12.98)、7.53(2.66～12.98)、0.30(0.28～0.33)。HA 的蛋白结合率大于60%，IS、PCS 及CMPF 的蛋白结合率均大于90%。结论HA、IS 及PCS 的游离浓度在CKD 后期出现升高，同时其蛋白结合率出现降低，CMPF 的游离浓度及蛋白结合率无明显变化。HA、IS、PCS 及CMPF 与血清白蛋白之间具有高强度结合。

关键词: 慢性肾脏病, 蛋白结合类尿毒症毒素, 游离浓度, 蛋白结合率

Abstract: Objective To detect the serum levels of free protein binding uremic toxins including hippuric acid (HA), indoxyl sulfate (IS), p-cresyl sulfate (PCS), and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) in patients with chronic kidney disease (CKD) and to calculate their albumin binding rates in order to understand the relationship between the serum concentrations of free protein binding uremic toxins, the protein binding rate, and renal function change. Method Free and total concentrations of serum HA, IS, PCS, and CMPF were measured in 10 healthy volunteers and 40 CKD patients. CKD patients were divided into CKD 3rd stage group, CKD 4th stage group, CKD 5th stage group, and maintenance hemodialysis (MHD) group. Free HA, IS, PCS and CMPF in serum were separated by ultrafiltration and measured by high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Serum albumin binding rates were then calculated. Results The serum levels (μg/ml) of free HA, IS, PCS and CMPF were 2.13 (1.36～3.53), 0.11 (0.07～017), 0.43 (0.14～0.59), and 0.26 (0.24～0.28), respectively, in healthy controls, 2.88 (1.76～ 5.63), 0.23 (0.05～0.48), 0.96 (0.56～2.08), and 0.30 (0.25～0.31), respectively, in CKD 3rd stage group, 8.78 (3.32～17.88), 0.55 (0.26～0.91), 1.21 (0.53～4.33), and 0.32 (0.29～0.50), respectively, in CKD 4th stage group, 24.05 (3.56～62.55), 3.16 (0.96～8.10), 5.42 (0.62～12.83), and 0.28 (0.25～0.35), respectively, in CKD 5th stage group, and 101.95 (23.23～125.25), 6.29 (2.06～12.98), 7.53 (2.66～12.98), and 0.30 (0.28～0.33), respectively, in MHD group. The protein binding rate was >60% for HA, and >90% for IS, PCS and CMPF. Conclusion Serum levels of free HA, IS, and PCS elevated in late CKD stages, and their protein- binding rates reduced as well. However, the serum level of free CMPF and its protein- binding rate changed insignificantly. HA, IS, PCS and CMPF bind to serum albumin tightly.

Key words: Chronic kidney disease, Protein-bound uremic toxin, Free concentration, Protein binding rate