rh-CSF1改善缺糖缺氧损伤神经元线粒体功能和细胞凋亡  

The rh-CSF1 improves mitochondrial function and cell apoptosis in neurons under oxygen-glucose deprivation

作　　者：刘蕊[1] 范宽 张鹏举 田雨 司玮 李世容[1] 王露[1] 顾然[1] 胡晓[1] LIU Rui;FAN Kuan;ZHANG Pengju;TIAN Yu;SI Wei;LI Shirong;WANG Lu;GU Ran;HU Xiao(Department of Neurology,Medical College of Guizhou University,Guizhou Provincial People’s Hospital,Guiyang 550002,China)

机构地区：[1]贵州省人民医院神经内科,贵阳550000

出　　处：《中国神经精神疾病杂志》2024年第8期489-494,共6页Chinese Journal of Nervous and Mental Diseases

基　　金：国家自然科学地区科学基金项目(编号:82060228);贵州省高层次人才创新创业择优资助项目(2021)(编号:05);贵州省科技厅支撑计划(编号:黔科合支撑[2021]一般077);贵州省中医药管理局中医药、民族医药科学技术研究课题(编号:QZYY-2023-052);贵州省卫生健康委科学技术基金项目(编号:gzwkj2023-006);贵州省高层次创新型人才项目(编号:黔科合平台人才-GCC[2023]029);贵州省科学技术厅基础研究计划(编号:黔科合基础-ZK[2023]一般225);贵州省人民医院青年基金项目(编号:GZSYQN202117);贵州省高层次创新型人才“千层次”人才项目(编号:GZSYQCC[2023]007)。

摘　　要：目的探讨集落刺激因子-1(colony stimulating factor-1,CSF1)抑制氧糖剥夺(oxygen-glucose deprivation,OGD)神经元凋亡的作用机制。方法采用大鼠原代大脑皮质神经元,分为OGD损伤神经元模型组(OGD组,n=3)、重组人CSF1(recombined human CSF1,rh-CSF1)干预组(rh-CSF1组,n=3)、对照组(n=3)。测定3组神经元凋亡率和其中三磷酸腺苷(adenosine triphosphate,ATP)含量,活性氧簇水平、线粒体膜电位和线粒体脱氧核糖核酸(deoxyribonucleic acid,DNA)拷贝数,检测线粒体内丙二醛含量和超氧化物歧化酶活性。结果OGD组模型进行基线评估,结果示神经元凋亡率、活性氧簇、线粒体内丙二醛水平、线粒体膜电位、线粒体DNA拷贝数、ATP含量、线粒体内超氧化物歧化酶活性与对照组有统计学差异(P<0.01)。rh-CSF1干预可提高OGD损伤后神经元的线粒体膜电位(0.55±0.03 vs.0.43±0.06,P<0.01)、线粒体DNA拷贝数(0.88±0.05 vs.0.72±0.06,P<0.05)、ATP含量([15.70±0.99)mmol/mg vs(.11.70±1.00)mmol/mg,P<0.01)]和线粒体内超氧化物歧化酶活性([18.47±1.38)U/mg vs.14.78±1.81)U/mg,P<0.05)],降低活性氧簇(3.64±0.21 vs.4.45±0.33,P<0.05)和线粒体内丙二醛水平([2.13±0.19)mmol/mg vs(.2.78±0.20)mmol/mg,P<0.05)],减轻神经元凋亡率。结论rh-CSF1可能通过改善线粒体功能、减轻氧化应激及抑制细胞凋亡,从而改善OGD诱导损伤神经元的受损程度。Objective To investigate the mechanism by which Colony Stimulating Factor-1(CSF1)inhibits apoptosis in neurons subjected to oxygen-glucose deprivation(OGD).Methods Primary rat cortical neurons were divided into the OGD damaged neuron model group(OGD group),the rh-CSF1 intervention group(rh-CSF1 group),and control group.The sample size for each group was 3.After intervention with recombinant human CSF1(rh-CSF1),neuronal apoptosis rate and intracellular ATP content,reactive oxygen species levels,mitochondrial membrane potential,and mitochondrial DNA copy number were measured.The content of malondialdehyde within mitochondria and the activity of superoxide dismutase were also assessed.Results Intervention with rh-CSF1 increased mitochondrial membrane potential(0.55±0.03 vs.0.43±0.06,P<0.01),mitochondrial DNA copy number(0.88±0.05 vs.0.72±0.06,P<0.05),ATP content[(15.70±0.99)mmol/mg vs.(11.70±1.00)mmol/mg,P<0.01)],and superoxide dismutase[(18.47±1.38)U/mg vs.(14.78±1.81)U/mg,P<0.05)]activity in neurons injured by OGD.It also reduced levels of rectivereactive oxygen species(3.64±0.21 vs.4.45±0.33,P<0.05)and malondialdehyde within mitochondria[(2.13±0.19)mmol/mg vs.(2.78±0.20)mmol/mg,P<0.05)],and inhibited neuronal apoptosis(10.12±0.78 vs.17.04±1.23,P<0.01)Conclusion rh-CSF1 may alleviate the damage in neurons induced by OGD by improving mitochondrial function,reducing oxidative stress,and inhibiting cell apoptosis.potential(0.55±0.03 vs.0.43±0.06,P<0.01),mitochondrial DNA copy number(0.88±0.05 vs.0.72±0.06,P<0.05),ATP content[(15.70±0.99)mmol/mg vs.(11.70±1.00)mmol/mg,P<0.01)],and superoxide dismutase[(18.47±1.38)U/mg vs.(14.78±1.81)U/mg,P<0.05)]activity in neurons injured by OGD.It also reduced levels of rectivereactive oxygen species(3.64±0.21 vs.4.45±0.33,P<0.05)and malondialdehyde within mitochondria[(2.13±0.19)mmol/mg vs.(2.78±0.20)mmol/mg,P<0.05)],and inhibited neuronal apoptosis(10.12±0.78 vs.17.04±1.23,P<0.01)Conclusion rh-CSF1 may alleviate the damage in neurons induced by OGD by i

关 键 词：集落刺激因子-1 缺糖缺氧 凋亡 氧化应激 线粒体功能 缺血性脑卒中 

分 类 号：R743.3[医药卫生—神经病学与精神病学]