Antioxidant effects of statins in patients with atherosclerotic cerebrovascular disease.
Antioxidant effects of statins in patients with atherosclerotic cerebrovascular disease.
复制标题
DOI：
10.3988/jcn.2014.10.2.140
复制
发表时间：
2014-04
期刊：
影响因子：
--
通讯作者：
Bang OY
中科院分区：
文献类型：
--
作者：
Moon GJ;Kim SJ;Cho YH;Ryoo S;Bang OY
氧化应激参与中风的病理生理机制（例如，动脉粥样硬化）和缺血性中风后的脑损伤。抑制3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶的他汀类药物具有多效性和降低低密度脂蛋白（LDL）的特性。最近的试验表明，大剂量他汀类药物可降低脑血管事件的风险。然而，关于动脉粥样硬化性卒中患者使用他汀类药物后氧化应激标志物变化的数据很少。本研究评估了动脉粥样硬化性卒中患者短期使用大剂量他汀类药物后氧化应激标志物的变化。99例动脉粥样硬化性卒中且既往未使用他汀类药物的患者接受瑞舒伐他汀20 mg/天给药。在给药前和给药后1个月采集血样，评价血清中4种氧化应激标志物-丙二醛（MDA）、氧化低密度脂蛋白（oxLDL）、蛋白羰基含量（PCO）和8-羟基-2 '-脱氧鸟苷（8-OHdG）-的水平，以分别测定这两个时间点的MDA和脂质、蛋白质和DNA的氧化。基线水平和他汀类药物使用后的减少程度在测量的氧化应激标志物之间存在差异。MDA和PCO水平与弥散加权成像的梗死体积相关（分别为r=0.551，p<0.05和r=0.444，p=0.05）。他汀类药物的使用降低了MDA和oxLDL水平（均p<0.05），但未降低PCO或8-OHdG水平。虽然他汀类药物治疗后MDA水平的降低与胆固醇的变化无关，但oxLDL水平的降低与胆固醇（r=0.479，p<0.01）、LDL（r=0.459，p<0.01）和载脂蛋白B（r=0.444，p<0.05）的降低成正比。缺血性中风后，个体氧化应激标志物的影响随着时间的推移而不同，这表明不同的氧化应激标志物反映了氧化应激的不同方面。此外，短期使用他汀类药物通过降脂依赖性和非依赖性机制对脂质过氧化产生抗氧化作用，但对动脉粥样硬化性卒中患者的蛋白质或DNA氧化无作用。
Oxidative stress is involved in the pathophysiological mechanisms of stroke (e.g., atherosclerosis) and brain injury after ischemic stroke. Statins, which inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, have both pleiotropic and low-density lipoprotein (LDL)-lowering properties. Recent trials have shown that high-dose statins reduce the risk of cerebrovascular events. However, there is a paucity of data regarding the changes in the oxidative stress markers in patients with atherosclerotic stroke after statin use. This study evaluated changes in oxidative stress markers after short-term use of a high-dose statin in patients with atherosclerotic stroke. Rosuvastatin was administered at a dose of 20 mg/day to 99 patients who had suffered an atherosclerotic stroke and no prior statin use. Blood samples were collected before and 1 month after dosing, and the serum levels of four oxidative stress markers-malondialdehyde (MDA), oxidized LDL (oxLDL), protein carbonyl content (PCO), and 8-hydroxy-2'-deoxyguanosine (8-OHdG)-were evaluated to determine the oxidation of MDA and lipids, proteins, and DNA, respectively, at both of those time points. The baseline levels and the degrees of reduction after statin use differed among the oxidative stress markers measured. MDA and PCO levels were associated with infarct volumes on diffusion-weighted imaging (r=0.551, p<0.05, and r=0.444, p=0.05, respectively). Statin use decreased MDA and oxLDL levels (both p<0.05) but not the PCO or 8-OHdG level. While the reduction in MDA levels after statin use was not associated with changes in cholesterol, that in oxLDL levels was proportional to the reductions in cholesterol (r=0.479, p<0.01), LDL (r=0.459, p<0.01), and apolipoprotein B (r=0.444, p<0.05). The impact of individual oxidative stress markers differs with time after ischemic stroke, suggesting that different oxidative markers reflect different aspects of oxidative stress. In addition, short-term use of a statin exerts antioxidant effects against lipid peroxidation via lipid-lowering-dependent and -independent mechanisms, but not against protein or DNA oxidation in atherosclerotic stroke patients.
登录
查看更多内容
影响因子：
11.2
作者：
Ay, H;Furie, KL;Koroshetz, WJ
通讯作者：
Koroshetz, WJ
影响因子：
4.7
作者：
Nagayama, T;Lan, J;Chen, J
通讯作者：
Chen, J
影响因子：
7.5
作者：
Correa, Maisa de Carvalho;Maldonado, Paula;Schetinger, Maria Rosa
通讯作者：
Schetinger, Maria Rosa
影响因子：
5.1
作者：
Demirkaya, S;Topcuoglu, MA;Vural, O
通讯作者：
Vural, O
影响因子：
8.3
作者：
Leinonen, JS;Ahonen, JP;Alho, H
通讯作者：
Alho, H