脂类在小鼠脑缺血再灌注恢复期的作用及机制

THE ROLE AND MECHANISM OF LIPIDS IN THE RECOVERY OF CEREBRAL ISCHEMIA-REPERFUSION IN MICE

董玱芮

11849368

硕士

生物学

侯圣陶

2020-06-04

2020-07-08

哈尔滨工业大学

深圳

脑卒中，也称为中风，是中国目前导致死亡和致残的主要疾病之一。全球每年有550万人因卒中死亡，因此将卒中的预防和治疗列为全球卫生重点。卒中的良好治疗可确保生活质量，这对个人、家庭和社会都有积极影响。尽管进行了大量的临床前和临床研究，已研究了一千多种候选神经保护性卒中药物并进行了约200项临床试验，但除组织型纤溶酶原激活剂外，尚未批准任何有效的治疗方法。一些研究表明抑制特定脂类代谢通路会导致细胞死亡或轴突再生。可是，对于脂类在卒中后的恢复期具体角色功能并不明确。本实验在前期使用脂组学系统性分析的方法对卒中后脂类展开研究，探讨缺血性卒中后大脑恢复期脂类分子的变化过程，并绘制恢复过程中脂类变化图谱。在体外通过免疫荧光染色和Time Lapse实时观测的方式，研究这些有显著差异的脂类分子对神经轴突树突的影响，以期揭示脂类分子在缺血性卒中后大脑恢复过程中调节神经元可塑性的机理；研究显著差异的脂类分子具体通过何种途径诱导细胞死亡。研究结果表明，其含量在大脑中动脉闭塞模型(Middle Cerebral Artery Occlusion , MCAO) 后小鼠恢复期3-7天显著提升的特定脂类（如LPC(16:0)）对神经元的可塑性恢复及存活率均有损伤作用，且钙离子结果暗示该脂类可能并非通过兴奋性毒性途径对神经元造成损伤。本文章研究了缺血性脑卒中恢复过程中脂组变化，为更好地理解生理性、病理性状态下脂类分子的变化奠定基础。研究脂类分子在该病中的作用机理，寻找在缺血性脑卒中康复过程中有益性或损伤性的脂类分子，探究它们对损伤神经元的作用及恢复机理，为开发新的有效的检测、治疗生物靶点提供强有力的理论基础，并对研发安全有效的治疗药物具有十分重要的意义。

Stroke, also known as stroke, is one of the leading causes of death and disability in China. 5.5 million people die of stroke every year worldwide, so stroke prevention is listed as a global health priority. A good treatment for stroke ensures the quality of life, which for individuals, families, and society all have positive a impact. Despite extensive pre-clinical and clinical research, more than 1,000 candidate neuroprotective stroke drugs have been studied and approximately 200 clinical trials have been conducted, but no effective treatment has been approved except for tissue-type plasminogen activators method. Some studies have shown that inhibition of specific lipid metabolism pathways can lead to cell death or axon regeneration. However, the specific role of lipids in the recovery period after stroke is not clear. This study used a systematic analysis of lipidomics to study lipids after stroke in the early stage, to explore the changes of lipid molecules in the cerebral recovery period after ischemic stroke, and to reveal a map of lipid changes during recovery. The effects of these significantly different lipid molecules on axon dendrites were studied in vitro using immunofluorescence staining and time lapse real-time observation to reveal that lipid molecules regulate neurons during brain recovery after ischemic stroke; how specific lipid molecules induce cell death. Our results showed that specific lipids [such as LPC (16: 0)] whose contents were being significantly increased in the 3-7 days of recovery after MCAO(Middle Cerebral Artery Occlusion) have a detrimental effect on the plastic recovery and survival rate of neurons, and in the calcium ion results, it is suggested that neurons may not be damaged through excitotoxic pathways. This study fills the blank of the study of lipid group changes during the recovery of ischemic stroke to better understand the map of lipid molecules in physiological and pathological states. It also investigates the role of lipid molecules in the disease, searches beneficial or damaging lipid molecules in the rehabilitation process of ischemic stroke, explores their effects on injured neurons and their recovery mechanisms, which provides a strong theoretical basis for the development of new and effective detection and treatment of biological targets, and is contributing to the development of safe and effective therapeutic drugs.

脑卒中 缺血再灌注 神经可塑性 脂质组学 神经元

Stroke Ischemia-Reperfusion Neuroplasticity Lipidomics Neurons

中文

联合培养

南方科技大学

董玱芮. 脂类在小鼠脑缺血再灌注恢复期的作用及机制[D]. 深圳. 哈尔滨工业大学,2020.