洋川芎内酯Ⅰ对氧糖剥夺/复氧大鼠原代大脑皮层神经元的影响  

Effects of senkyunolideⅠon oxygen and glucose deprivation/reoxygenation-induced injury in cerebral cortical neurons

作　　者：薛冰洁 姚尧尧 李丹溪[1,2,3] 任北大 高颖 XUE Bing-jie;YAO Yao-yao;LI Danxi;REN Bei-da;GAO Ying(Institute for Brain Disorders,Bejing University of Chinese Medicine,Bejing 100700,China;Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China;Chinese Medicine Key Research Room of Brain Disorders Syndrome and Treatment of the National Administration of Traditional Chinese Medicine,Beijing 100700,China;Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]北京中医药大学中医脑病研究院,北京100700 [2]北京中医药大学东直门医院,北京100700 [3]国家中医药管理局脑病中医证治重点研究室,北京100700 [4]北京中医药大学,北京100029

出　　处：《中华中医药杂志》2023年第1期106-110,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金青年科学基金项目(No.81703747)。

摘　　要：目的:研究洋川芎内酯Ⅰ(SENⅠ)对氧糖剥夺/复氧(OGD/R)大鼠原代大脑皮层神经元的保护作用,并探讨其相关的作用机制。方法:提取胎鼠原代大脑皮层神经元,预给药后进行OGD/R实验,分别评价细胞活力、细胞毒性,线粒体膜电势,ROS以及ATP生成的变化,并在此基础上探讨SENⅠ对cAMP依赖性蛋白激酶A(PKA)/环磷腺苷效应元件结合蛋白(CREB)通路的调控作用。结果:与模型组比较,SENⅠ50、100μmol/L组OGD神经元的细胞活力显著提高(P<0.01),SENⅠ25、50、100μmol/L组细胞毒性显著降低(P<0.01)。SENⅠ50、100μmol/L组OGD神经元线粒体膜电势水平及ATP水平显著升高(P<0.01),SENⅠ100μmol/L组ROS水平显著降低(P<0.05);SENⅠ100μmol/L组CREB的磷酸化水平显著升高(P<0.05)。结论:SENⅠ增加了OGD原代大脑皮层神经元的线粒体膜电势,调控了ROS和ATP的生成,保护OGD原代大脑皮层神经元,其可能的机制是通过激活CREB而发挥保护作用。Objective:To study the protective effect of senkyunolideⅠ(SENⅠ)on oxygen and glucose deprivation/reoxygenation(OGD/R)-induced injury in primary cerebral cortical neurons,and to explore the related mechanisms.Methods:The neurons were collected and the protocol was commenced following SENⅠexposure.We determined changes of cell viability,cytotoxicity,mitochondrial membrane potential,and generation of ROS and ATP.On this basis,the regulatory effect of SENⅠon PKA/CREB pathway were explored.Results:Compared with the model group,the neurons cell viability in SENⅠ50 and 100μmol/L group was significantly increased(P<0.01),and the cytotoxicity in SENⅠ25,50,and 100μmol/L groups was significantly decreased(P<0.01).The OGD neurons mitochondrial membrane potential and ATP in SENⅠ50 and 100μmol/L group were significantly increased(P<0.01),and the level of ROS was significantly reversed by SENⅠ100μmol/L group(P<0.05);the phosphorylation level of CREB was significantly increased in SENⅠ100μmol/L group(P<0.05).Conclusion:SENⅠreversed OGD/R-induced neuronal injury by increasing cell viability and the mitochondrial membrane potential,decreasing cytotoxicity,and regulating the generation of ROS and ATP.The possible mechanism is that SENⅠplays a protective role via activation of CREB.

关 键 词：洋川芎内酯Ⅰ 原代大脑皮层神经元 线粒体膜电势 活性氧 三磷酸腺苷 环磷腺苷效应元件结合蛋白 

分 类 号：R285.5[医药卫生—中药学]