蛋白结合类尿毒症毒素游离浓度及蛋白结合率的研究  

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

作　　者：任真真[1] 李新伦[1] 李红霞[1] 伦立德[1] 窦桂芳[2] 

机构地区：[1]中国人民解放军空军总医院肾病科,北京1001421 [2]军事医学科学院药代动力学研究室,北京1000912

出　　处：《中国血液净化》2015年第10期604-607,共4页Chinese Journal of Blood Purification

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。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.

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 

分 类 号：R969.1[医药卫生—药理学]