Hangaishi M, Nakajima H, Taguchi J, Igarashi R, Hoshino J, Kurokawa K, Kimura S, Nagai R, Ohno M
Department of Cardiovascular Medicine, University of Tokyo, Tokyo, Japan.
Biochem Biophys Res Commun. 2001 Aug 3;285(5):1220-5. doi: 10.1006/bbrc.2001.5319.
Covalent binding of 4 molecules of phosphatidylcholine palmitoyl to human recombinant superoxide dismutase (SOD) results in a compound (lecithinized SOD) that has a longer half-life and greater affinity to the cell membrane than unmodified SOD. We investigated whether lecithinized SOD played a protective role against myocardial ischemia-reperfusion injuries in rats. Rats underwent 45 min of myocardial ischemia by occluding the left coronary artery followed by 120 min of reperfusion. They were randomly assigned to receive either lecithinized SOD, polyethylene glycol conjugated SOD (PEG-SOD), unmodified SOD, free lecithin derivative, or PBS intravenously at 5 min prior to reperfusion. Myocardial infarct area assessed by TTC staining was smaller in lecithinized SOD group than PEG-SOD, unmodified SOD, free lecithin derivative or control group. Blood pressure and heart rate was similar in each group. ELISA demonstrated SOD level in the heart was significantly high in lecithinized SOD group, especially in the heart of ischemia at risk. Although serum SOD level of PEG-SOD was as high as lecithinized SOD, SOD level of the heart was low. These data suggested lecithinized SOD had a protective effect in myocardial ischemia-reperfusion injuries through its increased bioavailability.
4个磷脂酰胆碱棕榈酰分子与人重组超氧化物歧化酶(SOD)共价结合,产生一种化合物(卵磷脂化SOD),该化合物比未修饰的SOD具有更长的半衰期和对细胞膜更高的亲和力。我们研究了卵磷脂化SOD是否对大鼠心肌缺血-再灌注损伤起保护作用。大鼠通过阻断左冠状动脉经历45分钟的心肌缺血,随后进行120分钟的再灌注。在再灌注前5分钟,将它们随机分配接受静脉注射卵磷脂化SOD、聚乙二醇共轭SOD(PEG-SOD)、未修饰的SOD、游离卵磷脂衍生物或PBS。通过TTC染色评估的心肌梗死面积在卵磷脂化SOD组中比PEG-SOD、未修饰的SOD、游离卵磷脂衍生物或对照组小。每组的血压和心率相似。ELISA显示卵磷脂化SOD组心脏中的SOD水平显著升高,尤其是在有缺血风险的心脏中。尽管PEG-SOD的血清SOD水平与卵磷脂化SOD一样高,但心脏中的SOD水平较低。这些数据表明卵磷脂化SOD通过提高生物利用度对心肌缺血-再灌注损伤具有保护作用。