Dong Gao-xiang, Feng Yi-Pu
Department of Pharmacology, Institute of Materia Medica, CAMS, PUMC, Beijing 100050, China.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2002 Feb;24(1):93-7.
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).
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.
(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.
The results suggest that NBP improves energy pump and subsides oxidative injury which may contribute to its anti-neuronal apoptotic effect.
本研究旨在探讨(±)-3-正丁基苯酞(NBP)对大脑中动脉闭塞(tMCAO)2小时后再灌注24小时大鼠线粒体及大脑皮质中ATP酶、抗氧化酶活性和脂质过氧化的影响。
采用生化方法检测tMCAO大鼠线粒体或皮质中SOD(超氧化物歧化酶)、GSH-Px(谷胱甘肽过氧化物酶)、CAT(过氧化氢酶)的活性以及MDA水平。
(1)在溶剂组(缺血+生理盐水)中,线粒体Na+K(+)-ATP酶、Ca(2+)-ATP酶和Mg2+ATP酶的活性显著降低。在tMCAO前10分钟腹腔注射NBP(5、10、20mg/kg)预处理,与溶剂组相比,Na+K(+)-ATP酶和Ca(2+)-ATP酶的活性显著增强。(2)与假手术组(非缺血+生理盐水)相比,溶剂组中SOD和线粒体GSH-Px的活性降低,MDA水平升高。NBP(20mg/kg,腹腔注射)显著增强了线粒体总SOD活性,同时也增强了大脑皮质总SOD活性(5、10、20mg/kg组)。然而,它对CuZn-SOD活性没有明显影响。NBP(20mg/kg,腹腔注射)显著增加了线粒体(而非大脑皮质)GSH-Px活性;与溶剂组相比,NBP 10、20mg/kg显著降低了线粒体MDA水平(P<0.05)。(3)消旋NBP对ATP酶和抗氧化酶活性增加的作用似乎比(-)-NBP或(+)-NBP更有益。
结果表明,NBP可改善能量泵功能并减轻氧化损伤,这可能有助于其抗神经元凋亡作用。