L―精氨酸和天然抗氧化剂对缺血性脑卒中防治作用细胞和动物模型研究.docVIP

L―精氨酸和天然抗氧化剂对缺血性脑卒中防治作用细胞和动物模型研究 　　[摘 要] 目的 探讨L-精氨酸（L-Arginine，L-Arg）和天然抗氧化剂搭配组合对脑卒中的防治作用。方法 分别建立细胞的氧糖剥夺（oxygen and glucose deprivation，OGD）模型和小鼠的大脑中动脉闭塞（middle cerebral artery occlusion，MCAO）模型来模拟脑缺血，通过L-Arg和天然抗氧化剂搭配预处理之后分别检测细胞内活性氧（scavenge reactive oxygen species，ROS）水平、细胞凋亡及信号分子的表达。结果 低浓度L-Arg对细胞活力没有影响，但高浓度L-Arg能损伤细胞并影响Bcl-2和Bax表达。L-Arg和天然抗氧化剂搭配组合能够减轻OGD诱导细胞的损伤，对细胞活力有明显保护作用，清除OGD引起的细胞内产生的ROS增加，减少细胞凋亡和线粒体膜损伤并调节Bcl-2、Bax、caspase3的表达；在小鼠的MCAO模型中研究进一步发现，这个组合可以减轻局灶性脑缺血引起的脑组织损伤和脑组织细胞凋亡，调节Bcl-2和Bax的表达。结论 L-Arg和天然抗氧化剂搭配可以减少缺氧和缺血诱导的神经细胞和动物脑组织的损伤，可能对脑卒中有一定的防治作用。 　　[关键词] 一氧化氮；天然抗氧化剂；氧糖剥夺；缺血性脑卒中；细胞凋亡 　　中图分类号：R743.3文献标识码：A文章编号：1009-816X（2016）04-0259-05 　　[Abstract] Objective To study the preventive and therapeutic effects of L-Arginine （L-Arg） and natural antioxidants on ischemic stroke. Methods The model of oxygen and glucose deprivation （OGD） on cell and the model of Middle Cerebral Artery Occlusion （MCAO） on mice were established to simulate ischemic stroke. Reactive oxygen species （ROS） levels， apoptosis and signaling molecules in cell were detected respectively by a pretreatment with L-Arg and natural antioxidants. Results In vitro， a low concentration of L-Arg showed no effect on the cell vitality， but a high level of L-Arg could impair the cell and affect the expression of Bcl-2 and Bax. A reasonable combination of L-Arg and natural antioxidants could decrease OGD-induced cell damage and provide obvious protection on cell vitality by scavenging reactive oxygen species （ROS）， reducing apoptosis and mitochondrial membrane as well as modulating the expression of related proteins Bcl-2，Bax and caspase-3. In the study of the MCAO model on mice， we further discovered that this combination of L-Arg and natural antioxidants could decrease damage and the apoptosis of brain tissue， and modulate the expression of related proteins Bcl-2 and Bax induced by the focal brain ischemia. Conclusions Since a reasonable combination of L-Arg and natural antioxidants can reduce the dama