丁基苯酞对局部脑缺血再灌注大鼠脑线粒体ATPase,抗氧化酶活性和脂质过氧化的影响

Effects of NBP on ATPase and Anti-oxidant Enzymes Activities and Lipid Peroxidation in Transient Focal Cerebral Ischemic Rats

目的研究丁基苯酞对短暂性局部脑缺血大鼠脑线粒体ＡＴＰａｓｅ，抗氧化酶活性和脂质过氧化的影响。方法采用短暂性大脑中动脉阻断术（ｔＭＣＡＯ）模型，应用生物化学方法，测定神经细胞线粒体ＡＴＰａｓｅ活性，超氧化物歧化酶（ｓｕｐｅｒｏｘｉｄｅ ｄｉｓｍｕｔａｓｅ，ＳＯＤ），谷胱甘肽过氧化物酶（ｇｌｕｔａｔｈｉｏｎｅ ｐｅｒｏｘｉｄａｓｅ，ＧＳＨ－Ｐｘ），过氧化氢酶（ｃａｔａｌａｓｅ，ＣＡＴ）的活性和ＭＤＡ的含量。结果（１）大鼠ｔＭＣＡＯ后线粒体ＡＴＰａｓｅ活性均有不同程度的下降，于ｔＭＣＡＯ前１０ｍｉｎ腹腔注射丁基苯酞（ＮＢＰ）（５～２０ｍｇ ／ｋｇ）能明显升高线粒体Ｎａ＋Ｋ＋－ＡＴＰａｓｅ和Ｃａ ２＋ －ＡＴＰａｓｅ活性。（２）在缺血溶剂组，ＳＯＤ活性和线粒体ＧＳＨ－Ｐｘ活性显著下降，而ＭＤＡ的含量则明显升高。于缺血前１０ｍｉｎ，腹腔注射ＮＢＰ（２０ｍｇ ／ｋｇ）能明显增加缺血侧神经细胞线粒体和脑皮层总ＳＯＤ的活性，然而对ＣｕＺｎ－ＳＯＤ活性无明显作用。腹腔注射２０ｍｇ ／ｋｇ ＮＢＰ能显著升高线粒体ＧＳＨ－Ｐｘ的活性，而腹腔注射１０、２０ｍｇ ／ｋｇ ＮＢＰ能明显降低缺血脑线粒体ＭＤＡ的含量（Ｐ＜０．０５＝。（?

Objective The aim of the present study was designed to explore the effect of(±)-3-n-butylph-thalide(NBP)on ATPase,anti-oxidant enzymes activities and lipid peroxidation of mitochondria and cerebral cortex in rats subjected to24hours of reperfusion following2hours of cerebral ischemia(tMCAO).Methods Activities of SOD(Superoxide Dismutase),GSH-Px(glutathione Peroxidase,)and CAT(Catalase),and MDA level of mitochondria or cortex were measured by using biochemical met-hods in tMCAO rats.Results(1)The activities of mitochondrial Na + K + -ATPase,Ca 2+ -ATPase and Mg 2+ ATPase were found to decrese significantly in the vehicle group(ishemia+saline).Pre-treatment with NBP(5,10,20mg /kg,ip)10min before tMCAO markedly enhanced the activities of Na + K+-ATPase and Ca 2+ -ATPase,compared with vehicle group.(2)The activities of SOD and mitochondrial GSH-Px were decreased and MDA level increased in vehicle groups as compared with that in sham group(non is chemia+saline).NBP(20mg /kg,ip)significantly enhanced total mitochondrial SOD activity,and also enhanced cerebral cortex total SOD activity(in5,10,20mg /kg groups).However,it had no obvious effect on CuZn-SOD activity.NBP(20mg /kg ip)markedly increased mitochondrial(but not in cerebral cortex)GSH-Px activity;NBP10,20mg /kg markedly decreased mitochondrial MDA level compared with that in vehicle group (P<0.05=.(3)The action of raceme NBP on the increase of the activities of ATPase and antioxidative enzymes seemd to be beneficial than that of(-)-NBP or(+)NBP.Conclusion The results suggest that NBP improves energy pump and subsides oxidative injury which may contribute to its anti-neuronal apoptotic effect.