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

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性（tMACO）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的含理（P＜0．05）。（3）消旋NBP对提高Na^ K^ -ATPase,Ca^2 -ATPase活性和抑制线粒体氧化损伤的作用似乎较单独用（＋）－或（－）－NBP的好。结论：以上结果提示NBP改善线粒体能量泵,增加抗氧化作用是其发挥抗凋亡作用的重要原因。

Effects of NBP on ATPase and anti-oxidant enzymes activities and lipid peroxidation in transient focal cerebral ischemic rats

OBJECTIVE: The aim of the present study was designed to explore the effect of (+/-) -3-n-butylphthalide (NBP) on ATPase, anti-oxidant enzymes activities and lipid peroxidation of mitochondria and cerebral cortex in rats subjected to 24 hours of reperfusion following 2 hours 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 methods in tMCAO rats. RESULTS: (1) The activities of mitochondrial Na+K(+)-ATPase, Ca(2+)-ATPase and Mg2+ ATPase were found to decrease significantly in the vehicle group (ischemia + saline). Pre-treatment with NBP (5, 10, 20 mg/kg, i.p.) 10 min 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-ischemia + saline). NBP (20 mg/kg, i.p.) significantly enhanced total mitochondrial SOD activity, and also enhanced cerebral cortex total SOD activity (in 5, 10, 20 mg/kg groups). However, it had no obvious effect on CuZn-SOD activity. NBP (20 mg/kg i.p.) markedly increased mitochondrial (but not in cerebral cortex) GSH-Px activity; NBP 10, 20 mg/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 seemed 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.