ACEA改善线粒体复合体活性诱导神经保护作用研究

Effect of Mitochondrial Complex Activity on ACEA-induced Neuroprotection

目的:探讨线粒体复合体活性对大麻素CB1受体选择性激动剂ACEA神经保护作用的影响。方法:将原代大鼠皮层神经元分为4组:对照组(Control)、氧糖剥夺组(OGD)、ACEA+OGD组和溶剂(Vehicle)+OGD组,分别检测各组神经元损伤程度和线粒体复合体Ⅰ、Ⅱ和Ⅳ的活性。为进一步证实线粒体复合体活性对ACEA神经保护的影响,将原代大鼠皮层神经元分为5组:对照组(Control)、氧糖剥夺组(OGD)、ACEA+OGD组、线粒体复合体Ⅰ抑制剂(rotenone)+ACEA+OGD组和线粒体复合体Ⅱ抑制剂(TTFA)+ACEA+OGD组,检测和比较各组神经元细胞的损伤情况。结果:在OGD后24小时,ACEA明显增加神经元活性,减少LDH释放,降低神经元凋亡率(P<0.05),改善OGD损伤后线粒体复合体Ⅰ和Ⅳ的活性(P<0.05),而对复合体Ⅱ的活性没有影响;rotenone可以部分逆转ACEA的神经保护作用(P<0.05),但TTFA却没有这一作用。结论:ACEA可以诱导神经保护作用,其机制是与改善线粒体呼吸链复合体活性有关。

Objective： To investigate the effect of mitochondrial complex activity on cannabinoid CB1 receptor selective agonist ACEA-induced neuroprotection. Methods： The primary rat cortical neurons were divided into 4 groups： control group, OGD group,ACEA＋OGD group and Vehicle＋OGD group. The levels of neuron damage and the mitochondrial complex Ⅰ, Ⅱ and Ⅳ activity were detected respectively. To further confirm the effect of mitochondrial complex activity on ACEA neuroprotection, the primary rat cortical neurons were divided into 5 groups： Control group, OGD group, ACEA＋OGD group, mitochondrial complex Ⅰ inhibitor rotenone＋ACEA＋OGD group and mitochondrial complex Ⅱ inhibitor TTFA＋ACEA＋OGD group. The levels of neuron damage were detected and compared between different groups. Results： ACEA increased the cell viability, attenuated the LDH release and reduced the apoptosis rate of neurons at 24 h after reoxygenation（P0.05）. Moreover, ACEA improved the activity of mitochondrial complex Ⅰ and Ⅳ after OGD injury（P〈0.05）, but had no effect on the activity of mitochondrial complex Ⅱ. The protective effects of ACEA were partially abolished by mitochondrial complex Ⅰ inhibitor rotenone（P0.05）, while they were not reversed by mitochondrial complex Ⅱ inhibitor TTFA. Conclusion： ACEA could induce neuroprotective effects by improving mitochondrial complex activity.