State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Han kou Road No. 93, Nanjing, People's Republic of China.
Toxicol Lett. 2011 Feb 25;201(1):72-9. doi: 10.1016/j.toxlet.2010.12.007. Epub 2010 Dec 15.
Aristolochic acid (AA) nephropathy exhibits early proximal tubular injury and fatty acid metabolic disorder. In order to study the unrecognized abnormalities of organic ion transporters and fatty acid metabolism indicators in AA nephropathy, Wistar rats were orally administrated with vehicle, 10 and 20mg/kg AA once daily for 7 days, respectively. At day 8, significant reduction of body weight and right kidney weight, as well as elevation of plasma blood urea nitrogen (BUN) levels, renal long-chain fatty acids (LCFAs), non-esterified fatty acids (NEFA) and triglycerides (TG) contents were observed in AA-treated rats, accompanying with down-regulation of renal rOAT1/3, rOCT1/2 and rOCTN1/2 expressions. OCTN2 particularly transports l-carnitine through cell membrane. AA treatment also induced a significant decrease of L-carnitine levels in renal cortex of rats. Down-regulation of peroxisome proliferator-activated receptor alpha (rPPARα) and carnitine acyltransferase 1 (rCPT1), and up-regulation of acetyl coenzyme A carboxylase 1/2 (rACC1/2) in renal cortex were detected in AA-treated rats. These results indicate that alterations of organic ion transportation and fatty acid metabolism are part of AA-induced nephropathy (AAN), contribute to the altered urinary metabolic profile and may lead to further proximal tubule injury in rats.
马兜铃酸（AA）肾病表现为早期近端肾小管损伤和脂肪酸代谢紊乱。为了研究 AA 肾病中未被识别的有机离子转运体和脂肪酸代谢标志物的异常，将 Wistar 大鼠分别每天口服给予 vehicle、10 和 20mg/kg AA，连续 7 天。第 8 天，AA 处理组大鼠的体重和右肾重量显著降低，血浆血尿素氮（BUN）水平、肾脏长链脂肪酸（LCFAs）、非酯化脂肪酸（NEFA）和三酰甘油（TG）含量升高，同时肾 rOAT1/3、rOCT1/2 和 rOCTN1/2 表达下调。OCTN2 特别通过细胞膜转运左旋肉碱。AA 处理还诱导大鼠肾皮质中左旋肉碱水平显著降低。AA 处理组大鼠肾皮质中过氧化物酶体增殖物激活受体α（rPPARα）和肉碱脂酰转移酶 1（rCPT1）下调，乙酰辅酶 A 羧化酶 1/2（rACC1/2）上调。这些结果表明，有机离子转运和脂肪酸代谢的改变是 AA 诱导的肾病（AAN）的一部分，导致尿液代谢谱的改变，并可能导致大鼠进一步的近端肾小管损伤。
