Serkova Natalie, Klawitter Jost, Niemann Claus U
Department of Anesthesiology, University of Colorado Health Sciences Center, Denver, Colorado, USA.
Transpl Int. 2003 Oct;16(10):748-55. doi: 10.1007/s00147-003-0631-1. Epub 2003 Jun 24.
To evaluate organ-specific metabolic changes after in vivo cyclosporine (CyA) treatment, male Wistar rats were treated with 10 mg/kg per day CyA orally for 6 days. Blood, kidney, liver, and heart tissues were extracted and analyzed by magnetic resonance spectroscopy (MRS). CyA decreased the energy balance [adenosine triphosphate (ATP)/adenosine diphosphate (ADP)] in all organs (kidney [control]: 50%, liver: 64%, and heart: 62%, all P<0.01) due to decreased activity of the mitochondrial Krebs cycle and oxidative phosphorylation. As a compensatory effect, anaerobic glycolysis (lactate) was increased. This was reflected in the low glucose level in the kidney and heart, but not in the liver where a significant decrease in glycogen was seen. Only in the kidney was mitochondrial inhibition accompanied by decreased polyunsaturated fatty acid (PUFA) concentrations and elevated lipid peroxidation. The metabolic marker for nephrotoxicity, trimethylamine-N-oxide (TMAO), was elevated. While CyA decreased mitochondrial homeostasis in all organ systems, cellular adaptation was different and most efficient in the liver.
为评估体内环孢素（CyA）治疗后器官特异性代谢变化，将雄性Wistar大鼠每日口服10mg/kg CyA，持续6天。采集血液、肾脏、肝脏和心脏组织，并用磁共振波谱（MRS）进行分析。由于线粒体三羧酸循环和氧化磷酸化活性降低，CyA降低了所有器官的能量平衡[三磷酸腺苷（ATP）/二磷酸腺苷（ADP）]（肾脏[对照组]：50%，肝脏：64%，心脏：62%，均P<0.01）。作为一种代偿效应，无氧糖酵解（乳酸）增加。这反映在肾脏和心脏中的低葡萄糖水平，但在肝脏中未出现，肝脏中糖原显著减少。仅在肾脏中，线粒体抑制伴随着多不饱和脂肪酸（PUFA）浓度降低和脂质过氧化升高。肾毒性代谢标志物三甲胺-N-氧化物（TMAO）升高。虽然CyA降低了所有器官系统中的线粒体稳态，但细胞适应性不同，在肝脏中最为有效。
