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Spag6调控运动纤毛结构功能缓解大鼠缺血性脑水肿损伤

Spag6 Alleviated Brain Edema Injury Caused by Cerebral Ischemia-Reperfusion in Rats by Regulating Motor Cilia Structure and Function
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摘要 目的 研究精子相关抗原6(sperm-associated antigen 6,Spag6)对缺血性脑水肿介导的突触损伤的影响。方法 将90只SD大鼠随机分为3组:假手术组、模型组和Spag6组。利用慢病毒感染上调大鼠脑内Spag6蛋白表达后,用大脑中动脉栓塞法构建缺血性脑水肿模型。利用Longa评分进行神经功能评价;2,3,5-氯化三苯基四氮唑(TTC)染色评估脑梗死体积;苏木精-伊红(HE)染色法、扫描电镜观察运动纤毛结构活性;透射电镜观察神经细胞超微结构;Western blot检测Bcl-2、Bax、Survivin、GluN1、GluN2B和GluA2蛋白表达水平。结果 模型组大鼠大脑不同区域神经细胞和组织损伤,Spag6表达异常变化,突触结构功能改变;第三脑室运动纤毛活性紊乱,发生缺血性脑水肿现象。上调Spag6表达后,脑水肿现象缓解,运动纤毛活性恢复;缺血区脑梗死、神经细胞损伤及突触结构异常改变被逆转;Bcl-2、Survivin、GluN1、GluN2B、GluA2的蛋白表达显著升高(P<0.01或P<0.05),Bax表达量均降低(P<0.01)。结论 Spag6通过恢复脑室运动纤毛的活性状态,增强突触的功能,进而减轻缺血性脑水肿介导的神经损伤。 Objective To investigate the effect of sperm-associated antigen 6(Spag6)on cerebral edema secondary to ische-mia-reperfusion in rats.Methods Ninety SD rats were randomly assigned to three groups:sham operation group,model group,and experimental group.The rats were treated with lentivirus injection and middle cerebral artery embolization.The infarct vol-ume was evaluated by using 2,3,5-triphenyltetrazolium chloride(TTC)staining.Hematoxylin and eosin(HE)staining was used to observe the damage of ependymal cells and cilia.Scanning electron microscope was used to observe the activity of motile cili-a.Transmission electron microscopy was used to abserve the ultrastructure of nerve cells.The expressions of apoptosis-related proteins Bcl-2,Bax,Survivin,GluN1,GluN2B,and GluA2 were detected using Western blotting.Results After model construc-tion,nerve cells and tissues in different regions of the rat brain were damaged.Spag6 expression,synaptic structure and function were altered.The activity of motor cilia in the third ventricle was disturbed and ischemic cerebral edema was observed.After up-regulation of Spag6 expression,cerebral edema was relieved and the activity of motor cilia was restored.Ischemic cerebral infarc-tion,nerve cell injury and synaptic structural abnormalities were reversed.The protein expression of Bcl-2,Survivin,GluNl,GluN2B,and GluA2 increased significantly(P<0.01 or P<0.05),while the expression of Bax decreased(P<0.01).Conclusion Spag6 enhances synaptic function by restoring the active state of ventricular motor cilia,thereby alleviating ischemic brain edema mediated nerve damage.
作者 黄瑞松 胡一鸣 张配 张春艳 张玲 曹晓璐 Huang Ruisong;Hu Yiming;Zhang Pei(Institute of Pharmaceutical Process,Hubei Province Key Laboratory of Occupational Hazard Identification and Control,School of Medicine,Wuhan University of Science and Technology,Wuhan 430065,China;Environmental Toxicology Laboratory,Hubei Province Key Laboratory of Occupational Hazard Identification and Control,School of Public Health,Wuhan University of Science and Technology,Wuhan 430065,China;The Core Facility and Technical Support Center,Wuhan Institute of Virology,Chinese Academy of Sciences,Wuhan 430207,China)
出处 《华中科技大学学报(医学版)》 CAS CSCD 北大核心 2024年第3期295-301,307,共8页 Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
基金 国家自然科学基金资助项目(No.81801307) 湖北省高等学校优秀中青年科技创新团队项目(No.T2020003) 大学生创新创业训练计划项目(No.201810488010,No.201810488049)。
关键词 Spag6 脑缺血再灌注损伤 脑水肿 运动纤毛 突触 sperm-associated antigen 6 cerebral ischemia-reperfusion injury brain edema motor cilia synapse
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