Poirier B, Michel O, Bazin R, Bariéty J, Chevalier J, Myara I
INSERM U 430, Broussais Hospital and Claude Bernard Association, Paris, France.
Nephrol Dial Transplant. 2001 Aug;16(8):1598-606. doi: 10.1093/ndt/16.8.1598.
We assessed whether a differential oxidizability of apolipoprotein B (apo B)-containing lipoproteins (LDL and VLDL) may explain the oxidative stress that we had observed at the onset of renal fibrosis in Zucker obese (ZO) rats (Nephrol Dial Transplant 2000, 15: 467--476).
Ex vivo copper-induced oxidation of lipoproteins was performed in 1-, 3-, and 9-month-old ZO and age-matched lean (ZL) rats. LDL/VLDL oxidizability was determined by spectrophotometry at 234 nm by monitoring the formation of conjugated diene hydroperoxides.
A significant increase in lag time (reflecting the resistance to oxidation) was observed in ZO rats at 3 months while the maximal diene production (reflecting the amount of hydroperoxides formed during oxidation) was higher in ZO than in ZL rats as early as 1 month. Lipoproteins were larger in ZO than in ZL rats, as shown by their core to surface component ratio. Furthermore, ZO lipoproteins had increased vitamin E and polyunsaturated fatty acid (PUFA) content, with no change in vitamin E/PUFA ratio.
Rather than oxidizability of apo B-containing lipoproteins, the ability of these molecules to produce high levels of conjugated dienes, which can act as toxic tissue messengers, appears to be a critical trait in the development of renal fibrosis in this rat model of obesity and renal fibrosis.
我们评估了含载脂蛋白B（apo B）的脂蛋白（低密度脂蛋白和极低密度脂蛋白）的氧化差异是否可以解释我们在 Zucker 肥胖（ZO）大鼠肾纤维化发病时观察到的氧化应激（《肾脏病与透析移植杂志》2000年，第15卷：467 - 476页）。
对1、3和9月龄的ZO大鼠以及年龄匹配的瘦（ZL）大鼠进行离体铜诱导的脂蛋白氧化实验。通过在234nm处用分光光度法监测共轭二烯氢过氧化物的形成来测定低密度脂蛋白/极低密度脂蛋白的氧化能力。
在3月龄的ZO大鼠中观察到延迟时间显著增加（反映抗氧化能力），而早在1月龄时，ZO大鼠的最大二烯生成量（反映氧化过程中形成的氢过氧化物量）就高于ZL大鼠。从核心与表面成分比来看，ZO大鼠的脂蛋白比ZL大鼠的更大。此外，ZO大鼠的脂蛋白中维生素E和多不饱和脂肪酸（PUFA）含量增加，而维生素E/PUFA比值无变化。
在这种肥胖和肾纤维化大鼠模型中，肾纤维化发展的关键特征似乎不是含apo B脂蛋白的氧化能力，而是这些分子产生高水平共轭二烯的能力，共轭二烯可作为有毒的组织信使。
