摘要
目的基于氧化应激介导的PV中间神经元损伤研究银杏叶提取物治疗精神分裂症的作用机制。方法选取54只SPF级雄性小鼠为实验对象,分为空白组、模型组、银杏叶提取物50 mg·kg^(-1)、100 mg·kg^(-1)、150 mg·kg^(-1)组和利培酮组,通过腹腔注射MK-8010.3 mg·kg^(-1)建立精神分裂症小鼠模型,进行行为学(旷场实验、Y-迷宫、强迫游泳)检测,末次给药后24 h采集血液样本和脑组织,免疫荧光染色检测小鼠脑内PV神经元的变化;试剂盒检测血清中MAD、GSH-Px、SOD的含量;ELISA法检测小鼠脑组织内铁、脂质过氧化水平;Western blot法检测小鼠脑内GPX4的蛋白水平。结果与模型组相比,银杏叶提取物150 mg·kg^(-1)组和利培酮组,使Y迷宫的自发交替率显著降低,强迫游泳的不动时间显著缩短(P<0.05);PV神经元染色,不同程度的荧光强度增强;小鼠血清内的MDA含量明显降低(P<0.01),SOD和GSH-px的含量显著升高(P<0.05);小鼠脑内铁含量均显著降低(P<0.05),ROS含量均显著降低(P<0.05),小鼠脑内GPX4的含量均显著升高(P<0.05)。结论银杏叶提取物对MK-801所致的精神分裂症小鼠模型阴性症状及认知障碍均有明显的改善作用,并能改善精神分裂症小鼠前额叶皮层的PV神经元损伤,其机制可能与银杏叶提取物抑制铁死亡介导的氧化应激机制相关。
Objective To investigate the mechanism of action of Ginkgo biloba extract on schizophrenia based on oxidative stress-mediated damage to PV interneurons.Methods 54 SPF grade male mice were selected as experimental subjects,divided into blank group,model group,ginkgo biloba extract 50 mg·kg^(-1),100 mg·kg^(-1),150 mg·kg^(-1)group,and risperidone group.Schizophrenic mouse models were established by intraperitoneal injection of MK-8010.3 mg·kg^(-1),and behavioral(open field experiment,Y-maze,forced swimming)tests were conducted.Blood samples and brain tissue were collected 24 h after the last dose,Immunofluorescence staining was used to detect changes in PV neurons in the mouse brain;Detect the content of MAD,GSH Px,and SOD in serum using a reagent kit;ELISA method was used to detect the levels of iron and lipid peroxidation in mouse brain tissue;Western blot was used to detect the protein level of GPX4 in the mouse brain.Results Compared with the model group,the Ginkgo biloba leaf extract 150 mg·kg^(-1)group and the risperidone group significantly reduced the spontaneous alternation rate of the Y maze and significantly shortened the immobility time of forced swimming(P<0.05);PV neuron staining with varying degrees of enhanced fluorescence intensity;The MDA content in the serum of mice was significantly reduced(P<0.01),while the contents of SOD and GSH px were significantly increased(P<0.05);The iron content in the mouse brain was significantly reduced(P<0.05),the ROS content was significantly reduced(P<0.05),and the GPX4 content in the mouse brain was significantly increased(P<0.05).Conclusion Ginkgo biloba extract has a significant improvement effect on negative symptoms and cognitive impairment in MK-801 induced schizophrenia mouse models,and can also improve PV neuron damage in the prefrontal cortex of schizophrenia mice.Its mechanism may be related to the inhibition of iron death mediated oxidative stress by Ginkgo biloba extract.
作者
张红丽
王昆
段超慧
季明财
曾思涵
吕孝媛
ZHANG Hongli;WANG Kun;DUAN Chaohui;JI Mingcai;ZENG Sihan;LYU Xiaoyuan(Baotou Medical College,Baotou 014040,China;Inner Mongolia Baogang Hospital,Baotou 014040,China)
出处
《世界科学技术-中医药现代化》
北大核心
2025年第5期1368-1375,共8页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
内蒙古自治区科学技术厅内蒙古自治区自然科学基金一般联合基金项目(2025LHMS08022):基于小胶质细胞糖代谢重编程研究银杏叶提取物对精神分裂症的治疗机制,负责人:张红丽
包头市卫生健康科技计划项目(wsjkkj030):基于代谢组学研究银杏叶提取物对精神分裂症动物模型能量代谢的影响,负责人:张红丽
包头医学院科学研究基金项目青苗计划项目(BYJJ-ZRQM 202307):银杏叶提取物对精神分裂症动物模型的治疗作用及神经免疫学机制研究,负责人:张红丽。
