Metabolomic profiling of the autosomal dominant polycystic kidney disease rat model
Metabolomic profiling of the autosomal dominant polycystic kidney disease rat model
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DOI：
10.1007/s10157-011-0467-4
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发表时间：
2011-10-01
影响因子：
2.3
通讯作者：
Abe, Takaaki
中科院分区：
文献类型：
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作者：
Toyohara, Takafumi;Suzuki, Takehiro;Abe, Takaaki
常染色体显性多囊肾病（ADPKD）是一种遗传性全身性疾病，以肾囊肿扩张为特征，导致肾功能衰竭。随着肾损害的进展，尿毒症化合物的积累随后引起进一步的肾损害和高血压。寻找尿毒症毒素和敏感标志物检测ADPKD的早期阶段是必要的，以明确其病理生理过程和防止其发展。本研究利用Han:SPRD大鼠模型，采用毛细管电泳-质谱（CE-MS）分析了ADPKD的尿毒症保留溶质谱。方法采用CE-MS对汉族：SPRD大鼠和对照大鼠的297个阳离子和190个阴离子进行综合分析。结果与对照组相比，杂合型（Cy/+） ADPKD大鼠模型中有21个阳离子和19个阴离子显著积累。其中，在ADPKD Cy/+大鼠中新发现5-甲基-2′-脱氧胞苷、葡萄糖胺、外托因、尿囊酸盐、α -羟基苯甲酸盐、苯乙酸盐和3-苯丙酸盐含量增加，2-脱氧胞苷、癸酸盐和10-羟基癸酸盐含量减少。结论我们在ADPKD Cy/+大鼠中发现了尿毒症保留溶质。与ADPKD相关的化合物可作为早期检测ADPKD的有用标记物。
Background Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disease characterized by renal cyst expansion, resulting in renal failure. With the progression of renal damage, the accumulation of uremic compounds is recently reported to subsequently cause further renal damage and hypertension. Finding uremic toxins and sensitive markers for detecting the early stage of ADPKD is necessary to clarify its pathophysiological process and to prevent its progression. The aim of this study was to analyze the profile of uremic retention solutes of ADPKD by capillary electrophoresis-mass spectrometry (CE-MS) using the Han:SPRD rat model.Methods Two hundred and ninety-seven cations and 190 anions were comprehensively analyzed by CE-MS in Han: SPRD rats and control rats.Results We found 21 cations and 19 anions that accumulated significantly in the heterozygous (Cy/+) ADPKD rat model compared with control rats. Among the compounds, increases in 5-methyl-2'-deoxycytidine, glucosamine, ectoine, allantoate, alpha-hydroxybenzoate, phenaceturate and 3-phenylpropionate and decreases in 2-deoxycytidine, decanoate and 10-hydroxydecanoate were newly identified in the ADPKD Cy/+ rats.Conclusion We identified uremic retention solutes in ADPKD Cy/+ rats. Compounds related to ADPKD could be useful markers for detecting the early stage of ADPKD.