摘要
目的:探讨铁死亡通路中的谷胱甘肽代谢失衡与中风病发病的关系,描绘关键代谢物及核心蛋白在中风前后表达与分布变化。方法:应用TUNEL染色评估模型有效性。通过非靶向代谢组学表征大鼠中风前后血浆和脑组织代谢轮廓的变化和潜在代谢通路;在此基础上,采取平行反应监测技术对中风前后大鼠血浆和脑组织中铁死亡代谢通路进行靶向代谢组学和靶向蛋白质组学研究。结果:与假手术组比较,模型组大脑缺血区域细胞明显坏死;大脑中胱氨酸转运体SLC3A2显著下调;参与谷胱甘肽生物合成的上游物质谷氨酰胺、甘氨酸及胱硫醚含量下调;同时参与合成过程的关键酶GSS与GCLC表达量减少;对细胞铁死亡起到关键抑制作用的GPX4含量明显下降。结论:谷胱甘肽代谢失衡是细胞铁死亡通路中的关键环节,参与了大脑缺血再灌注损伤的病理过程。本研究对其中关键代谢物与核心蛋白在血-脑双系统中表达与分布进行了描绘,通过现代科学语言注释了中风病。
Objective:To explore the relationship between stroke and glutathione metabolic-disorder which resulting in ferroptosis,as well as profile the expression and distribution changes of metabolites and proteins in brain and plasma before and after stroke.Methods:Validity of MCAO/R model was evaluated with TUNEL staining.Non-targeted metabolism was applied for profiling the metabolic changes brought by ischemic injury and exploring the regulatory pathways.Further,parallel reaction monitoring was employed for confirmations on targeted molecules in plasma and brain tissue.Results:Marked cell necrosis was observed in the ischemic area of model group brains.The contents of important molecules of glutathione biosynthesis,including upstream factors of glutamin,glycine and cystathionine;key enzymes of GSS and GCLC;and negative regulator of ferroptosis GPX4,were found significantly down-regulated in the MCAO/R brains.Conclusion:Glutathione metabolic-disorder plays a key role in the ferroptosis pathway.It is illustrated to be involved in the pathological process of cerebral ischemia-reperfusion injury.This study describes the expression and distribution changes of key metabolites and core proteins in the blood-brain dual system,and provides annotations for the concept as well as the mechanism of stroke.
作者
邓欣祺
王哲义
张雨婷
刘窈玉
王雨青
王家平
卢涛
王春国
DENG Xin-qi;WANG Zhe-yi;ZHANG Yu-ting;LIU Yao-yu;WANG Yu-qing;WANG Jia-ping;LU Tao;WANG Chun-guo(School of Life Science,Beijing University of Chinese Medicine,Beijing 102488,China;Beijing Research Institute of Chinese Medicine,Beijing University of Chinese Medicine.Beijing 102488,China;School of Traditional Chinese Medicine,Beijing University of Chinese Medicine,Beijing 102488,China;School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China)
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2021年第4期2000-2005,共6页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
国家自然科学基金项目(No.81703744)。
