丁基苯酞对线粒体呼吸链复合酶活性的影响

EFFECTS OF BUTYLPHTHALIDE ON THE ACTIVITIES OFCOMPLEXES OF THE MITOCHONDRIAL RESPIRATORY CHAIN

目的：阐明正丁基苯酞（ｄｌ３ｎｂｕｔｙｌｐｈｔｈａｌｉｄｅ，ｄｌＮＢＰ）改善缺血脑能量代谢的机制。方法：用分光光度法测定局灶性脑缺血大鼠脑线粒体呼吸链复合酶Ｉ，Ｉ，ＩＩ和ＩＶ活性的改变，并观察ｄｌＮＢＰ对这些变化的影响。结果：缺血时复合酶ＩＩ活性升高，ＩＶ的活性显著降低；再灌后，复合酶Ｉ活性升高，ＩＩ的活性降低。在缺血前１０ｍｉｎ给予ｄｌＮＢＰ（５ｍｇ·ｋｇ－１或１０ｍｇ·ｋｇ－１，ｉｐ）能逆转缺血再灌引起的上述复合酶活性改变，尤其是使缺血后急剧降低的复合酶ＩＶ活性得到明显提高。同时ＮＢＰ（ｄ，ｌ，ｄｌ）还能逆转低糖低氧造成的原代培养大鼠皮质细胞呼吸链复合酶ＩＶ活性降低。结论：ＮＢＰ能够改善缺血脑内能量状态是直接作用于脑线粒体的结果，而ｄＮＢＰ起着主要作用。

AIM: To study the effect of dl3nbutylphthalide(dlNBP) on the function of mitochondrial respiratory chain and to elucidate the increasing effect of NBP on brain energy supply during cerebral ischemia. METHODS: Mitochondria were isolated from the brain of transient middle cerebral artery occluded (MCAO) rat and the activities of the four complexes of the respiratory chain were determined. RESULTS: The activity of complex IV was deeply decreased after 1 hischemia. It was back to normal level when treated with NBP (5 mgkg-1 or 10 mgkg-1 ip 10 min before ischemia). During the reperfusion period after ischemia, the activity of complex I was notably increased at 3 h, and that of complex II was decreased at 6 h. With NBP treatment, these altered activities also returned to normal level. In cultured neurons subjected to 6 hhypoxia/hypoglycemia, the same increasing effect of NBP(d,l or dl) on the activity of complex IV was also found, and dNBP seemed to be more effective. CONCLUSION: NBP can act direct ly on complex IV to increase its activity. This action may play an important role in the increasing effect of NBP on brain energy supply during cerebral ischemia.