Effect of the antioxidant N,N'-diphenyl 1,4-phenylenediamine (DPPD) on atherosclerosis in apoE-deficient mice.
Effect of the antioxidant N,N'-diphenyl 1,4-phenylenediamine (DPPD) on atherosclerosis in apoE-deficient mice.
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抗氧化剂 N,N-二苯基 1,4-苯二胺 (DPPD) 对 apoE 缺陷小鼠动脉粥样硬化的影响。
DOI：
10.1161/01.atv.15.10.1625
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Palinski,W
中科院分区：
文献类型：
--
作者：
Tangirala,RK;Casanada,F;Miller,E;Witztum,JL;Steinberg,D;Palinski,W
载脂蛋白(Apo)E缺陷小鼠会出现动脉粥样硬化病变，其中包含在脂蛋白氧化修饰过程中形成的表位，并且它们表现出针对这些表位的高滴度循环自身抗体，这表明该小鼠株可能提供一个模型来研究氧化脂蛋白导致动脉粥样硬化的机制(Palinski等，Arterioscler Thromb)。1994年；14：605-616)。为了验证载脂蛋白氧化有助于载脂蛋白E缺陷小鼠病变形成的假设，我们研究了抗氧化剂N，N‘-二苯基1，4-苯二胺(DPPD)对喂饲含0.15%胆固醇的高脂饮食小鼠的影响。动物被分成性别和血浆胆固醇水平匹配的两个亚组，其中一个亚组的饮食中添加了DPPD(0.5%wt/wt)。在干预的6个月中，DPPD治疗对血浆胆固醇没有显著影响。实验结束时的血浆DPPD水平为33.1mol/L，根据对多不饱和脂肪酸丢失的抵抗力判断，DPPD处理组动物的脂蛋白(d<；1.019 g/m L)比对照组动物的脂蛋白对铜诱导的氧化的抵抗力更强。此外，在DPPD处理的小鼠的低密度脂蛋白和IDL组分中，形成共轭双烯的滞后时间延长了两倍以上。动脉粥样硬化显著减轻，DPPD治疗组小鼠动脉粥样硬化显著减少36%(14.0±4.53%的主动脉表面积比21.9±11.6%；n=32；P<；0.02)。这些结果与脂蛋白氧化促进载脂蛋白E缺陷小鼠动脉粥样硬化形成的假设是一致的。然而，需要对其他抗氧化剂进行进一步的研究来验证这一假设。
Apolipoprotein (apo) E–deficient mice develop atherosclerotic lesions that contain epitopes formed during the oxidative modification of lipoproteins, and they demonstrate high titers of circulating autoantibodies against such epitopes, suggesting that this murine strain may provide a model to investigate the atherogenic mechanisms of oxidized lipoproteins (Palinski et al,Arterioscler Thromb. 1994;14:605-616). To test the hypothesis that lipoprotein oxidation contributes to lesion formation in apoE-deficient mice, we studied the effect of the antioxidantN,N′-diphenyl 1,4-phenylenediamine (DPPD) in mice fed a high-fat diet containing 0.15% cholesterol. Animals were divided into two subgroups matched for sex and plasma cholesterol levels, and DPPD (0.5% wt/wt) was added to the diet of one subgroup. Throughout the 6 months of intervention, DPPD treatment had no significant effect on plasma cholesterol. Plasma levels of DPPD at the end of the experiment were 33.1 μmol/L. As judged by resistance to loss of polyunsaturated fatty acids, lipoproteins (d<1.019 g/mL) from DPPD-treated animals showed greater resistance to copper-induced oxidation than lipoproteins from control animals. In addition, there was a greater than twofold prolongation of the lag time in the formation of conjugated dienes in the LDL and IDL fractions of DPPD-treated mice. Atherosclerosis was significantly reduced, by 36% in the DPPD-treated mice (14.0±4.53% of aortic surface area versus 21.9±11.6%; n=32;P<.02). These results are consistent with the hypothesis that lipoprotein oxidation contributes to atherogenesis in apoE-deficient mice. However, further studies with other antioxidants are needed to validate this hypothesis.