NIM811对Na_(2)S_(2)O_(4)引起小鼠HT22细胞缺氧/复氧损伤的保护作用的研究  

Protective effect of NIM811 on hypoxia/reoxygenation injury of hippocampal neurons in mice

作　　者：王丹[1,2] 赵承军 陈桂生[2,4] WANG Dan;ZHAO Chengjun;CHEN Guisheng(Clinical College of Ning Xia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学临床学院,宁夏银川750004 [2]宁夏颅脑疾病重点实验室,宁夏银川750004 [3]宁夏医科大学医学科学技术研究中心,宁夏银川750004 [4]宁夏医科大学总医院神经内科,宁夏银川750004

出　　处：《中风与神经疾病杂志》2022年第2期100-103,共4页Journal of Apoplexy and Nervous Diseases

基　　金：国家自然科学基金(81560209)。

摘　　要：目的探讨环孢菌素衍生物NIM811对连二亚硫酸钠(Na_(2)S_(2)O_(4))引起的小鼠海马神经元细胞(HT22)的缺氧/复氧损伤的保护作用及其机制。方法以小鼠HT22培养细胞制备缺氧/复氧细胞模型,实验分组为正常对照组、Na_(2)S_(2)O_(4)组、Na_(2)S_(2)O_(4)+NIM811组、NIM811组。CCK-8检测细胞生存率、流式细胞术检测细胞凋亡、JC-1试剂检测线粒体膜电位、用钙离子指示剂Rhod-2 AM观察线粒体内钙离子水平、DCFH-DA法检测细胞活性氧(ROS)水平。结果与Na_(2)S_(2)O_(4)组比较,给予NIM811处理后:(1)细胞活性增高38%(P<0.01);(2)细胞凋亡减少27%(P<0.01);(3)线粒体膜电位上升(P<0.01);(4)线粒体内钙离子水平下降(P<0.01);(5)活性氧(ROS)水平降低(P<0.01)。结论NIM811对Na_(2)S_(2)O_(4)引起小鼠海马神经元细胞缺氧/复氧损伤有保护作用,其机制可能为NIM811维持线粒体动态平衡和抑制细胞凋亡有关,NIM811对未来临床治疗缺血性脑卒中具有潜力。Objective To investigate the protective effect and mechanism of the derivative NIM811 on hypoxia/reoxygenation injury of rat hippocampal neuron(HT22)induced by sodium disulfite(Na_(2)S_(2)O_(4)).Methods The hypoxia/reoxygenation cell model was prepared with mouse HT22 cultured cells.The experiment was divided into normal control group,Na_(2)S_(2)O_(4) group,Na_(2)S_(2)O_(4)+NIM811 group,and NIM811 group.Cell survival rate was detected by CCK-8,flow cytometry was used to detect apoptosis,mitochondrial membrane potential was detected by JC-1 reagent,calcium ion level in mitochondria was observed by Rhod-2 AM,and reactive oxygen species(ROS)was detected by DCFH-DA method.Results Compared with the Na_(2)S_(2)O_(4) group,after NIM811 treatment:(1)Cell activity increased by 38%(P<0.01);(2)Apoptosis decreased by 27%(P<0.01);(3)Mitochondrial membrane potential increased(P<0.01);(4)The level of calcium ions in the mitochondria decreased(P<0.01);(5)The level of reactive oxygen species(ROS)decreased(P<0.01).Conclusion NIM811 has a protective effect on the hypoxia/reoxygenation injury of mouse hippocampal neurons caused by Na_(2)S_(2)O_(4).The mechanism may be related to the maintenance of mitochondrial homeostasis and inhibition of cell apoptosis.NIM811 has therapeutic potential for future clinical treatment of ischemic stroke.

关 键 词：NIM811 缺氧/复氧 活性氧 线粒体动力学 细胞凋亡 

分 类 号：R743[医药卫生—神经病学与精神病学]