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基于 GC-MS 代谢组学的大鼠肝脏代谢谱时序性变化的性别差异研究
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戴鑫华,向 瑾,常艳波,范玮豪,杨 虹,杨 林,叶 懿,廖林川 1. 四川大学 华西基础医学与法医学院四川 成都 6100412. 四川大学 华西医院实验医学科四川 成都 610041 
基金项目:国家自然科学基金资助项目(82072111);四川省科技厅重点研发项目(2019YFS0066)
中文摘要:考察性别因素对死后肝脏组织中代谢物变化规律的影响。72只SD大鼠(雌雄各半)于死后72 h内不同时间采集肝脏右叶,进行气相色谱-质谱联用(Gas chromatography-mass spectrometry,GC-MS)代谢组学分析。通过主成分分析(Principal component analysis,PCA)和偏最小二乘法(Partial least squares,PLS)进行多元统计分析,筛选出不同性别中均随死亡时间(Postmortem interval,PMI) 变化的共同差异代谢物,比较分析其在死后不同时间是否存在性别差异。结果显示,雌雄大鼠肝脏的不同PMI样本在PCA和PLS分析中均能完全区分,在雄性大鼠和雌性大鼠肝脏中分别筛选出了42种和41种与PMI相关的差异代谢物,其中31种为不同性别组共有的差异代谢物。在共有的差异代谢物中,有18种在死后不同时间点存在性别差异。该研究表明性别因素会对死后不同时间肝脏组织中代谢物的浓度产生影响,采用代谢物推断PMI时需考虑性别因素。
中文关键词:死亡时间  代谢组学  气相色谱-质谱联用  肝脏  性别
 
Study on Rats Gender Difference by Liver Metabolic Profiling Based on GC-MS Metabolomics
Abstract:Postmortem Interval(PMI) estimation is important in investigation of crime. However, the PMI is susceptible to various endogenous and exogenous factors. The objective of this work is to investigate the influence of gender on the postmortem changes of metabolites in liver tissue by gas chromatography-mass spectrometry(GC-MS). Seventy-two Sprague-Dawley(SD) rats(half males and half females) were mechanically asphyxiated and stored under the conditions of controlled humidity and temperature. The cadaveric phenomena were observed and recorded according to PMI(0, 6, 12, 24, 48, 72 h). The right liver lobes were collected by dissection at the predesignated PMIs. The whole metabolome was analyzed by GC-MS after the sample was preprocessed. After data preprocessing, multivariate statistical analyses were performed by principal component analysis(PCA) and partial least squares(PLS). The variable Importance in the Projection(VIP) and Kruskal-Wallis(K-W) test were used to select the common differential metabolites related to the PMI of both genders. The gender differences of PMI related metabolites were analyzed. The liver samples of both genders at different times after death could be completely distinguished by PCA and PLS, respectively. The results of 7-fold cross validation and 200 times replacement validation of PLS model showed that the model fitted well. Forty-two metabolites in male rat liver were selected based on VIP values and K-W test, and 41 metabolites were selected in female rat liver. Thirty-one common differential metabolites(59.6%) were both related to PMI, including amino acids, fatty acids, biogenic amines and other endogenous metabolites or postmortem catabolites. Eighteen of them showed gender differences. There were two types of metabolites with gender differences in lives: metabolites with gender difference at 0 h and other time points, and metabolites with gender difference after 24 h. This work shows that gender has an effect on the changes of metabolites in different tissues, and gender should not be ignored when metabolites are used for PMI estimation.
Key Words:postmortem interval  metabolomics  gas chromatography-mass spectrometry  liver  gender
引用本文:戴鑫华,向 瑾,常艳波,范玮豪,杨 虹,杨 林,叶 懿,廖林川.基于 GC-MS 代谢组学的大鼠肝脏代谢谱时序性变化的性别差异研究[J].分析测试学报,2021,40(9):1303-1310.
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