The metabolic profile of a rat model of chronic kidney disease.
The metabolic profile of a rat model of chronic kidney disease.
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作者：
Tanada Y;Okuda J;Kato T;Minamino-Muta E;Murata I;Soga T;Shioi T;Kimura T
肾脏总是受到高代谢的需求。本研究的目的是描述慢性肾脏病（CKD）伴心肾综合征（CRS）大鼠模型的代谢特征。我们使用近交系雄性Dahl盐敏感（DS）大鼠从6周龄开始喂食8%NaCl饮食（高盐; HS组）或0.3%NaCl饮食作为对照（低盐; LS组）。分析肾脏的功能、病理、代谢组学以及与能量代谢相关的基因表达。高盐饮食的DS大鼠在11周龄时表现出高血压，在21周龄时血清肌酐和血尿素氮水平升高并伴有心力衰竭。肾脏的纤维化面积在21周龄时增加。此外，与线粒体功能相关的基因表达大幅下降。柠檬酸盐和异柠檬酸盐水平增加，α-酮戊二酸脱氢酶和琥珀酰辅酶A合成酶的基因表达降低;这些酶分别代谢柠檬酸盐和异柠檬酸盐。此外，琥珀酸和乙酰辅酶A的水平，这两者都是三羧酸（TCA）循环的代谢产物，下降。高盐饮食喂养的DS大鼠被认为是CKD伴CRS的合适模型。高血压DS大鼠肾脏与能量代谢和线粒体相关的基因表达和代谢产物的变化与肾损伤的进展一致。
The kidney is always subjected to high metabolic demand. The aim of this study was to characterize metabolic profiles of a rat model of chronic kidney disease (CKD) with cardiorenal syndrome (CRS) induced by prolonged hypertension. We used inbred male Dahl salt-sensitive (DS) rats fed an 8% NaCl diet from six weeks of age (high-salt; HS group) or a 0.3% NaCl diet as controls (low-salt; LS group). We analyzed function, pathology, metabolome, and the gene expression related to energy metabolism of the kidney. DS rats with a high-salt diet showed hypertension at 11 weeks of age and elevated serum levels of creatinine and blood urea nitrogen with heart failure at 21 weeks of age. The fibrotic area in the kidneys increased at 21 weeks of age. In addition, gene expression related to mitochondrial function was largely decreased. The levels of citrate and isocitrate increased and the gene expression of alpha-ketoglutaratedehydrogenase and succinyl-CoA synthetase decreased; these are enzymes that metabolize citrate and isocitrate, respectively. In addition, the levels of succinate and acetyl Co-A, both of which are metabolites of the tricarboxylic acid (TCA) cycle, decreased. DS rats fed a high-salt diet were deemed a suitable model of CKD with CRS. Gene expression and metabolites related to energy metabolism and mitochondria in the kidney significantly changed in DS rats with hypertension in accordance with the progression of renal injury.