Renoprotective effects of fenofibrate in diabetic rats are achieved by suppressing kidney plasminogen activator inhibitor-1
Renoprotective effects of fenofibrate in diabetic rats are achieved by suppressing kidney plasminogen activator inhibitor-1
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DOI：
10.1016/j.vph.2006.01.004
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发表时间：
2006-05-01
影响因子：
4
通讯作者：
Wang, Bao-Ping
中科院分区：
文献类型：
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作者：
Chen, Lu-Lu;Zhang, Jiao-Yue;Wang, Bao-Ping
为探讨非诺贝特对糖尿病大鼠肾脏保护作用的机制，将雄性Wistar大鼠分为对照组、糖尿病未治疗组和非诺贝特治疗组（32 mg/kg·d ~（-1），8周）。用链脲佐菌素（25 mg/kg）和高脂饲料诱发糖尿病，表现为血糖和血脂紊乱。糖尿病未治疗组肾小球体积、基质含量、层粘连蛋白表达及尿白蛋白排泄均增加。这些肾病与肾皮质中纤溶酶原激活物抑制剂1（派-1）mRNA表达及其蛋白活性的上调以及转化生长因子β 1（TGF-β 1）表达的显著增加相关。非诺贝特治疗抑制PAI-Ⅰ mRNA表达及其蛋白活性，抑制TGF-β 1过表达。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糖尿病肾病大鼠的进展。这些肾保护作用可能通过抑制肾皮质中的派-1和TGF-β 1，从而减少细胞外基质沉积来实现。(c)2006年爱思唯尔公司All rights reserved.
To investigate mechanisms of protective effects of fenofibrate on the diabetic kidney, male Wistar rats were divided into control, untreated diabetes, and fenofibrate-treated (32mg kg(-1) d(-1), 8weeks) diabetes groups. Diabetes induced by streptozotocin (25mg/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 beta 1 (TGF-beta 1) expression. Treatment with fenofibrate suppressed the expression of PAI-I mRNA and its protein activity, and inhibited TGF-beta 1 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-beta 1 in the renal cortex, and consequently less extracellular matrix deposition. (c) 2006 Elsevier Inc. All rights reserved.