Chen Lu-Lu, Zhang Jiao-Yue, Wang Bao-Ping
Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Vascul Pharmacol. 2006 May;44(5):309-15. doi: 10.1016/j.vph.2006.01.004. Epub 2006 Apr 19.
To investigate mechanisms of protective effects of fenofibrate on the diabetic kidney, male Wistar rats were divided into control, untreated diabetes, and fenofibrate-treated (32 mg kg(-1) d(-1), 8 weeks) diabetes groups. Diabetes induced by streptozotocin (25 mg/kg) and a high-fat diet was characterized by the disorders of plasma glucose and lipids. In untreated diabetic rats, there were increases in glomerular volume, matrix content, expressions of laminin and urinary albumin excretion. These nephropathies were associated with the upregulations of plasminogen activator inhibitor 1 (PAI-1) mRNA expression and its protein activity in the renal cortex, and a significant increase in transforming growth factor beta1 (TGF-beta1) expression. Treatment with fenofibrate suppressed the expression of PAI-I mRNA and its protein activity, and inhibited TGF-beta1 overexpression. It also partially reversed metabolic disorders and pathophysiologic changes associated with diabetic nephropathy. Our results indicate that fenofibrate delays the progression of diabetic nephropathy in rats to some extent. These renoprotective effects are likely to be achieved through suppression of PAI-1 and TGF-beta1 in the renal cortex, and consequently less extracellular matrix deposition.
为研究非诺贝特对糖尿病肾病的保护作用机制，将雄性Wistar大鼠分为对照组、未治疗糖尿病组和非诺贝特治疗（32毫克/千克/天，8周）糖尿病组。链脲佐菌素（25毫克/千克）和高脂饮食诱导的糖尿病以血糖和血脂紊乱为特征。在未治疗的糖尿病大鼠中，肾小球体积、基质含量、层粘连蛋白表达和尿白蛋白排泄增加。这些肾病与肾皮质中纤溶酶原激活物抑制剂1（PAI-1）mRNA表达及其蛋白活性上调以及转化生长因子β1（TGF-β1）表达显著增加有关。非诺贝特治疗可抑制PAI-1 mRNA表达及其蛋白活性，并抑制TGF-β1的过度表达。它还部分逆转了与糖尿病肾病相关的代谢紊乱和病理生理变化。我们的结果表明，非诺贝特在一定程度上延缓了大鼠糖尿病肾病的进展。这些肾脏保护作用可能是通过抑制肾皮质中的PAI-1和TGF-β1，从而减少细胞外基质沉积来实现的。
