Pravastatin suppress superoxide and fibronectin production of glomerular mesangial cells induced by oxidized-LDL and high glucose
Pravastatin suppress superoxide and fibronectin production of glomerular mesangial cells induced by oxidized-LDL and high glucose
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DOI：
10.1016/s0021-9150(01)00545-7
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发表时间：
2002-01-01
期刊：
影响因子：
5.3
通讯作者：
Lai, YH
中科院分区：
文献类型：
--
作者：
Chen, HC;Guh, JY;Lai, YH
普伐他汀是一种有效的HMG-CoA还原酶抑制剂，可有效降低血脂水平。最近的研究表明，普伐他汀还可以减少LDL的氧化修饰，减少糖尿病患者的蛋白尿。为了确定普伐他汀对糖尿病肾脏的可能益处，我们检测了普伐他汀对氧化低密度脂蛋白和高糖刺激的肾小球系膜细胞增殖、超氧化物和纤连蛋白产生以及纤连蛋白mRNA表达的影响。我们的结果表明，[H-3]标记的胸腺嘧啶核苷的系膜细胞摄取减少后，氧化LDL刺激（50 μ g/ml，6 h），并在高糖刺激后增加（25 mM，48 h），氧化LDL或高糖刺激后肾小球系膜细胞超氧化物歧化酶和纤连蛋白的产生及纤连蛋白mRNA的表达均显著增加，或氧化低密度脂蛋白和高葡萄糖的组合。普伐他汀（100 μ M，48小时）单独对未刺激的细胞没有影响。然而，普伐他汀显着逆转氧化低密度脂蛋白或高糖刺激后肾小球系膜细胞的胸苷摄取，抑制超氧化物和纤连蛋白的产生，并抑制纤连蛋白mRNA的表达。我们的研究结果表明，普伐他汀可能作为一种抗氧化剂，并可能抑制肾小球系膜细胞纤维连接蛋白的合成在糖尿病合并高脂血症患者。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
Pravastatin is a potent inhibitor of HMG-CoA reductase and is effective in lowering serum lipid levels. Recent studies have shown that pravastatin also reduces oxidative modification of LDL and decreases albuminuria in patients with diabetes. To determine the possible benefit of pravastatin on the diabetic kidney, we have measured the effects of pravastatin on the proliferation and the production of superoxide and fibronectin, and the expression of fibronectin mRNA of glomerular mesangial cells stimulated by oxidized-LDL and high glucose. Our results demonstrated that the [H-3]-labeled thymidine uptake of mesangial cells decreased after oxidized-LDL stimulation (50 mug/ml, 6 h) and increased after high glucose stimulation (25 mM, 48 h), The production of superoxide and fibronectin and the expression of fibronectin mRNA of glomerular mesangial cells were all significantly increased after stimulation with either oxidized-LDL or high glucose, or the combination of oxidized-LDL and high glucose. Pravastatin (100 muM, 48 h) alone had no effect on unstimulated cells. However, pravastatin significantly reversed thymidine uptake, inhibited the production of superoxide and fibronectin, and inhibited the expression of fibronectin mRNA of glomerular mesangial cells after stimulation with either oxidized-LDL or high glucose. Our results indicate that pravastatin may effect as an antioxidant and may suppress fibronectin synthesis of glomerular mesangial cells in diabetic patients with hyperlipidemia. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.