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作 者:罗志刚[1] 何菁菁[1,3] 贺玖明[1] 再帕尔·阿不力孜[1,2]
机构地区:[1]中国医学科学院/北京协和医学院药物研究所,天然药物活性物质与功能国家重点实验室,北京100050 [2]中央民族大学生物成像与系统生物学研究中心,北京100081 [3]教育部高等教育教学评估中心,北京100081
出 处:《分析测试学报》2017年第2期178-183,共6页Journal of Instrumental Analysis
基 金:国家重大科学仪器设备开发专项资助(2011YQ170067)
摘 要:以添加镇静催眠候选新药N6-羟苄腺嘌呤核苷[N6-(4-hydroxybenzyl)adenine riboside,NHBA]的组织匀浆切片作为考察对象,对空气动力辅助离子化质谱成像系统(Air Flow Assisted Ionization Mass Spectrometry Imaging,AFAI-MSI)的关键参数进行考察与优化,以保证最佳条件进行样品检测。在此基础上,对预处理的整体大鼠组织切片进行平行的连续两次质谱成像分析,考察了其内源性代谢物在成像分析过程中是否发生变化。通过对采集数据中关键质谱峰的筛选等处理步骤,并采用可视化的主成分分析(PCA)方法,开展了组织样品内源性代谢物的稳定性分析,最终验证了采用该样品前处理和质谱成像方法,能够保证组织切片样品中内源性代谢物的稳定性,为质谱成像分析结果提供了可靠依据。Key parameters of air flow assisted ionization mass spectrometry imaging(AFAI-MSI)system were investigated and optimized by using tissue sections adding homogeneous NHBA as the target samples. The parameters,including those related with spray solvent,spray gas,as well as geometric setting of AFAI system were optimized. Based on the optimization,stability of endogenous metabolites from the tissue section was also taken into consideration during the AFAI-MSI experiment.It usually takes 7-8 h for a complete MSI experiment for a whole-body tissue section,and the stability of endogenous metabolites needs to be investigated during such a long process. Therefore, a whole-body tissue section was imaged twice consecutively,and then the data of resulted images were compared using visualized component principle analysis(PCA) after selecting main mass spectra peaks. By visualized comparing of the result,the similarity of the visualized PCA score plot demonstrated the endogenous metabolites were stable during MSI experiment. In conclusion,the optimized parameters guaranteed the stability and sensitivity of AFAI-MSI experiment. Additionally, after proper sample pretreatment,the endogenous metabolites in tissue sections were able to remain stable during the AFAI-MSI experiment,which ensured the reliability for research of the variability of endogenous metabolites. Thus the AFAI-MSI method is promising to be applied in the study of drug development.
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