Vascular Biology Center and Department of Physiology, Medical College of Georgia, Augusta, Georgia, USA.
Toxicol Mech Methods. 2005;15(2):125-36. doi: 10.1080/15376520590918856.
Abstract The number of obese people in the world is growing rapidly worldwide and has reached epidemic status. Obesity is often associated with the clustering of metabolic and cardiovascular risk factors that contribute to metabolic syndrome or syndrome X. Likewise, metabolic syndrome and its associated traits are major contributing factors to the increase in nephropathy and end stage renal disease. The specific factors that link the metabolic syndrome traits to the progression of nephropathy remain largely unexplored. Recent studies have demonstrated that an imbalance between cyclooxygenase-2 (COX-2) and cytochrome P450 (CYP450) arachidonic acid metabolizing enzymes in the kidney may contribute to the renal damage associated with obesity. Along these lines, COX-2 inhibition decreases renal cytokine levels and glomerular injury in obese rats. Peroxisome proliferators-activated receptors (PPARs) are transcription factors that also contribute to chronic kidney disease in obesity and metabolic syndrome. Intriguingly, interactions between PPARs and arachidonic acid metabolites could be key determinants of renal damage in metabolic syndrome patients. Therefore, there is a promising future for pharmacological agents that manipulate COX-2 and CYP450 metabolites and PPARs to treat obesity related nephropathy.
全球肥胖人口数量迅速增长，已达到流行态势。肥胖通常与代谢和心血管危险因素聚集相关，这些因素促成了代谢综合征或综合征 X。同样，代谢综合征及其相关特征是导致肾病和终末期肾病发生率增加的主要因素。将代谢综合征特征与肾病进展联系起来的具体因素在很大程度上仍未得到探索。最近的研究表明，肾脏中环氧化酶-2（COX-2）和细胞色素 P450（CYP450）花生四烯酸代谢酶之间的失衡可能导致与肥胖相关的肾脏损伤。沿着这些思路，COX-2 抑制可降低肥胖大鼠的肾脏细胞因子水平和肾小球损伤。过氧化物酶体增殖物激活受体 (PPAR) 是转录因子，也会导致肥胖和代谢综合征中的慢性肾病。有趣的是，PPAR 与花生四烯酸代谢物之间的相互作用可能是代谢综合征患者肾脏损伤的关键决定因素。因此，操纵 COX-2 和 CYP450 代谢物以及 PPAR 的药物有望成为治疗肥胖相关肾病的方法。
