Sarm1基因在创伤性脑损伤中的作用  

The role of Sarm1 gene in traumatic brain injury

作　　者：刘潜 于欣宇 车益军 曹芳 冉启山 Liu Qian;Yu Xinyu;Che Yijun;Cao Fang;Ran Qishan(Graduate School of Zunyi Medical University,Zunyi Guizhou 563099,China;Department of Neurosurgery,Affiliated Hospital of Zunyi Medical University,Zunyi Guizhou 563099,China;Guizhou Provincial Key Laboratory of Brain Science,Zunyi Medical University,Zunyi Guizhou 563099,China)

机构地区：[1]遵义医科大学研究生院,贵州遵义563099 [2]遵义医科大学附属医院神经外科,贵州遵义563099 [3]遵义医科大学贵州省普通高等学校脑科学特色重点实验室,贵州遵义563099

出　　处：《遵义医科大学学报》2022年第5期567-575,共9页Journal of Zunyi Medical University

基　　金：国家自然科学基金资助项目(NO:81860241);贵州省基础研究计划项目(NO:黔科合基础〔2019〕1354);贵州省卫生健康委员会资助项目(NO:gzwkj2021-191)。

摘　　要：目的通过建立控制性皮质损伤(CCI)模型,探讨CCI后Sarm1对小鼠脑组织神经损伤程度、轴突损伤、神经元死亡及小鼠行为学的影响,为后续创伤性脑损伤的治疗提供新的理论依据。方法(1)分别构建野生型小鼠和Sarm1基因敲除小鼠CCI模型,于建模成功后第1、3、5、7天,用转棒实验评价Sarm1对CCI后小鼠的神经功能的影响。(2)运用7T MRI对小鼠进行活体扫描,T2像观察两组小鼠创伤灶部位脑组织损伤程度,并通过DTI像扫描,检测FA值比较Sarm1对CCI后小鼠轴突损伤的影响。(3)免疫荧光及Western blot检测APP表达,进一步验证CCI后Sarm1对神经轴突损伤的影响。(4)免疫组化检测神经核抗原(NeuN),检测CCI后Sarm1对小鼠神经元活性的影响。结果(1)Sarm1基因敲除鼠在伤后第1、3、5天小鼠运动功能相较于野生组显著改善。(2)Sarm1基因敲除鼠在伤后第1天创伤部位损伤范围较野生组明显减少;Sarm1敲除鼠在伤后第1天损伤灶FA值的降低程度较WT组明显减轻。(3)CCI后,Sarm1基因敲除组APP表达较野生组明显减少。(4)Sarm1敲除鼠较WT组损伤灶周边NeuN表达明显增高,说明Sarm1敲除后,对神经元损伤起到明显的保护作用。结论创伤性脑损伤后,敲除Sarm1可减轻脑组织损伤,抑制轴突损伤及神经元死亡从而发挥神经保护作用。Objective In this study,we established a controlled cortical injury(CCI)model to explore the effects of Sarm1 gene on brain injury,axon injury and neuron death after CCI,so as to provide a new theoretical basis for subsequent treatment of traumatic brain injury.Method(1)The CCI model of wild-type mice and Sarm1 knock-out mice was constructed,respectively,and the effect of Sarm1 on the neural function of post-CCI mice was evaluated by turning rod experiment on the 1st,3rd,5th and 7th days after successful modeling.(2)The 7T MRI was used to scan the mice in vivo,and the T2 image observed the degree of brain tissue damage at the trauma foci of the two groups of mice,and the FA value was compared with the impact of Sarm1 on the axonal damage of mice after CCI by DTI phase scan.(3)Immunofluorescence and Western blot detect APP expression to further verify the effect of Sarm1 on axonal damage after CCI.(4)Neuronuclear antigen(NeuN)was detected by immunohistochemistry,and the effect of Sarm1 on neuronal activity of mice after CCI was detected.Results(1)Sarm1 gene knock-out rats had significant improvements in motor function compared with the wild group on day 1,day 3,and day 5 after injury.(2)The extent of injury in Sarm1 gene knock-out rats was significantly reduced compared with that in the wild group on the first day after injury,and the reduction in the FA value of the injury lesion on the first day after injury was significantly reduced compared with that in the WT group.(3)After CCI,APP expression in the Sarm1 gene knock-out group was significantly reduced compared with that in the wild group.(4)NeuN expression in Sarm1 knock-out mice was significantly higher than that in WT group,indicating that Sarm1 knock-out has a significant protective effect on neuron injury.Conclusion After traumatic brain injury,Sarm1 gene knockout can relieve brain tissue damage,inhibit axon injury and neuronal death,thus playing a neuroprotective role.

关 键 词：创伤性脑损伤 轴突损伤 Sarm1 APP 

分 类 号：R651.15[医药卫生—外科学]