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作 者:韩沾元[1] 陈铭[1] 王庆华[1] 周兆年[1]
机构地区:[1]中国科学院上海生理研究所
出 处:《生理学报》1994年第1期36-43,共8页Acta Physiologica Sinica
基 金:中国科学院上海生理研究所低氧生理开放实验室资助
摘 要:单甲氧基聚乙二醇(MPEG)活化后与超氧化物歧化酶(SOD)偶联,经纯化后得到MPEG-SOD,鉴定其分子量约为7.0×105Dation。其在血液循环中酶活性半衰期超过30h,远大于天然SOD(6-10min)。SD雄性大鼠分三组.对照组(n=8.由股静脉注入0.2ml生理盐水)、NativeSOD组(n=8,注以0.2ml生理盐水配的800USOD)和MPEG-SOD组(n=9,注以800UMPEG-SOD)。低氧前三组鼠的心率(HR)、左室内峰压(LVP)、左室压微分(LV±dp/dtmax)和股动脉压(AP)均无统计学差别。在模拟6000—6500m高度急性低氧1.8.14min记录上述各项指标,结果如下:除HR外,NativeSOD组与对照组各指标均无统计学差别,MPEG-SOD组的各项指标均明显高于对照组。表明MPEG-SOD对急性低氧导致的左心室力学指标的减弱有明显保护作用,提示超氧自由基(O2-)在急性低氧导致左心室功能损伤中起重要作用,即可能是由O2-及其衍生的其它自由基损害心肌细胞生物膜系统所致。Monomethoxypolyethylene glycol(MPEG) was attached covalently to superoxide dismutase (SOD, EC1. 15. 1.1). The molecular weight of MPEG-SOD was about 7. 0 ×105 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 (PR0. 05, PR0. 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.
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