早期白假丝酵母血流感染大鼠模型的血浆代谢组学分析

为探寻白假丝酵母(又称白念珠菌)早期感染的血浆代谢标记，采用尾静脉注射白念珠菌方法建立大鼠白念珠菌感染模型。将20只大鼠按随机数字法分为对照组和白念珠菌组，每组10只。应用超高效液相色谱-四级杆飞行时间串联质谱(ultra-high performance liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry，UHPLC-Q-TOF-MS)技术结合数据依赖性采集方式检测大鼠血浆中的代谢物，采用SIMCA-P软件对所测数据分别进行偏最小二乘法判别分析(partial least squares discrimination analysis，PLS-DA)、正交偏最小二乘法判别分析(orthogonal PLS-DA，OPLS-DA)及主成分分析(principal component analysis，PCA)，以进行模式识别，区分白念珠菌组与正常对照组血浆代谢物的差异。根据OPLS-DA模型的变量投影重要度(variable importance in the projection，VIP)筛选可能的代谢标记。结果显示，白念珠菌组与对照组的血浆代谢物存在明显差异，OPLS-DA、PLS-DA及PCA模型均可区分两组，初步确认了18个正离子模式鉴定的差异物，对应化合物可能是大鼠念珠菌感染的潜在标记。受试者工作特征曲线(receiver operating characteristic curve，ROC)分析发现，LysoPC(14∶0)、LysoPC(18∶1(9Z))、LysoPC(18∶0)、L-Tryptophan、L-Gulonic acid γ-lactone这5个代谢物ROC的曲线下面积均＞0.90。本研究初步筛选出早期白念珠菌感染的可能代谢生物标记，可为白念珠菌感染早期诊断和治疗提供理论基础。

Plasma metabonomics analysis of Candida albicans bloodstream infection in early stage in rat model

The present paper aimed to find the metabolic biomarkers of Candida albicans (C. albicans) infection in early stage. The model of C. albicans-infected Wistar rats was established by tail vein injection of C. albicans liquid. Twenty rats were divided into control group and C. albicans group according to the random number table, 10 in each group. The samples were analyzed by ultra-high performance liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS) combined with data-dependent acquisition. The measured data were analyzed using SIMCA-P software. Partial least squares discrimination analysis (PLS-DA), orthogonal PLS-DA (OPLS-DA) and principal component analysis (PCA) were used for pattern recognition analysis, respectively, to distinguish the differences in plasma metabolites between the C. albicans group and the control group. The possible metabolic markers were screened according to the variable importance in the projection (VIP) values of OPLS-DA model. The results showed that plasma metabolites in the two groups differed significantly. The OPLS-DA, PLS-DA and PCA models were effective methods to distinguish the two groups. The differences in 18 metabolites were preliminary confirmed. Receiver operating characteristic curve (ROC) analysis demonstrated that the areas under ROC (AUCs) of LysoPC (14∶0), LysoPC (18∶1(9Z)), LysoPC (18∶0), L-tryptophan, L-gulonic acid γ-lactone were all higher than 0.90. The study indicates that the corresponding compounds might be potential markers of Candida infection in Wistar rats, which may help the early diagnosis and treatment of C. albicans infection.