谷氨酸和皮质酮诱导的PC12抑郁症细胞模型差异性的~1H NMR代谢组学研究  

Comparative study of the corticosterone and glutamate induced PC12 cells depression model by ~1H NMR metabolomics

作　　者：何小燕[1] 陈建丽[1] 向欢[2] 高耀[1] 田俊生[1] 秦雪梅[1] 杜冠华[3] 

机构地区：[1]山西大学中医药现代研究中心,北京100050 [2]山西大学体育学院,山西太原030006 [3]中国医学科学院北京协和医学院药物研究所,北京100050

出　　处：《药学学报》2017年第2期245-252,共8页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81441096);山西省科技计划资助项目(201603D321077);山西省科技创新重点团队资助项目(201605D131045-18);山西省重点实验室资助项目(201605D111004)

摘　　要：应用~1H NMR代谢组学技术分析皮质酮(corticosterone,CORT)和谷氨酸(glutamate,Glu)诱导PC12细胞后,细胞及其培养液中代谢产物的变化,比较诱导后的细胞与空白对照组代谢产物的差异性,并结合多元统计分析和代谢通路分析探讨两种诱导方式所致抑郁症细胞模型的特点,为抑郁症疾病研究中模型的选择及作用机制研究提供依据。结果显示在CORT刺激下,细胞内外共发现36个差异代谢产物;Glu刺激下细胞内外发现42个差异代谢产物。其中,两种方式刺激后细胞内外相同的差异代谢物分别有13个和19个。相关性分析结果显示CORT刺激下,丝氨酸和2-氧基异亮氨酸与多数差异代谢物相关;Glu刺激下,乳酸和谷胱甘肽与多数差异代谢物相关;由此推测,CORT刺激下,其影响的主要是脂肪和脂肪酸的转化以及细胞膜结构,而Glu刺激下,主要对糖酵解过程以及抗氧化过程有影响。This study was designed to analyze the change of metabolites in the PC12 cells and its medium induced by corticosterone（CORT） and glutamate（Glu） by proton nuclear magnetic resonance（^1H NMR） metabolomics. The multivariate statistical analysis was employed to identify the difference between control groups and induced groups,respectively. In addition,metabolite pathway analysis was performed to explore the characteristic of CORT-induced and or Glu-induced PC12 cells depression model,and to provide the references for the selection of in vitro depression models as well as the further understanding of the mechanism on depressive disorders. We found 36 differential metabolites in CORT-induced PC12 cells and medium and 42 in Glu-induced PC12 cells. Furthermore,correlation analysis results show that serine and 2-oxoisoleucine were associated with most differential metabolites in CORT-induced PC12 cells. Lactate and glutathione were significantly correlated to the vast majority of differential metabolites in Glu-induced PC12 cells. We speculated that CORT-induced PC12 cell models may affect the fatty acid metabolism and cell membrane structure,and Glu-induced PC12 cell models may have a difference in the glycolysis and antioxidants.

关 键 词：代谢组学 皮质酮 谷氨酸 PC12细胞 抑郁症模型 

分 类 号：R969[医药卫生—药理学]