Han Z Y, Chen M, Wang Q H, Zhou Z N
Physiological Laboratory of Hypoxia, Shanghai Institute of Physiology, Chinese Academy of Sciences.
Sheng Li Xue Bao. 1994 Feb;46(1):36-43.
Monomethoxypolyethylene glycol (MPEG) was attached covalently to superoxide dismutase (SOD, EC1.15.1.1). The molecular weight of MPEG-SOD was about 7.0 x 10(5) Dalton determined by Fast Protein Liquid Chromatography (FPLC with Sepharose 6 HR10/30). MPEG-SOD exhibited a sharply enhanced serum half life (more than 30 h) than that of the native SOD (6-10 min). To determine the role of MPEG-SOD in acute hypoxia-induced injury of left ventricular function, heart rate (HR), arterial pressure (AP), left ventricular pressure (LVP) and dp/dt (LV +/- dp/dtmax) were measured in male SD rats divided into three groups: Control group (n = 8, intravenously injected with physiological saline), native SOD group (n = 8,800 U SOD i. v.) and MPEG-SOD group (n = 9,800 U MPEG-SOD i. v.). LVP, LV +/- dp/dtmax, AP and HR showed no significant difference among these three groups before hypoxia. But in acute hypoxia simulating altitude of 6,000-6,500 m, LVP, LV+dp/dtmax and AP were decreased in the control group, while in MPEG-SOD group they were all increased compared with those in control group (P < 0.05, P < 0.01). There were no significant difference between control group and native SOD group. The results indicate that MPEG-SOD has a protective effect on the injury of myocardial function induced by acute hypoxia, and suggest that acute hypoxia cause increase of superoxide free radical (O2.-) and other derivative radicals damaging membrane system of the cell.
单甲氧基聚乙二醇(MPEG)共价连接到超氧化物歧化酶(SOD,EC1.15.1.1)上。通过快速蛋白质液相色谱法(使用琼脂糖6 HR10/30的FPLC)测定,MPEG-SOD的分子量约为7.0×10⁵道尔顿。与天然SOD(6 - 10分钟)相比,MPEG-SOD的血清半衰期显著延长(超过30小时)。为了确定MPEG-SOD在急性低氧诱导的左心室功能损伤中的作用,将雄性SD大鼠分为三组,测量心率(HR)、动脉压(AP)、左心室压(LVP)和dp/dt(左心室±dp/dtmax):对照组(n = 8,静脉注射生理盐水)、天然SOD组(n = 8,静脉注射800 U SOD)和MPEG-SOD组(n = 9,静脉注射800 U MPEG-SOD)。在低氧之前,这三组的LVP、左心室±dp/dtmax、AP和HR没有显著差异。但在模拟海拔6000 - 6500米的急性低氧状态下,对照组的LVP、左心室+dp/dtmax和AP降低,而MPEG-SOD组与对照组相比均升高(P < 0.05,P < 0.01)。对照组和天然SOD组之间没有显著差异。结果表明,MPEG-SOD对急性低氧诱导的心肌功能损伤具有保护作用,并提示急性低氧导致超氧阴离子自由基(O₂⁻)和其他衍生自由基增加,从而损害细胞的膜系统。