Chronic unpredictive mild stress leads to altered hepatic metabolic profile and gene expression.
Chronic unpredictive mild stress leads to altered hepatic metabolic profile and gene expression.
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DOI：
10.1038/srep23441
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发表时间：
2016-03-23
影响因子：
4.6
通讯作者：
Zou ZM
中科院分区：
文献类型：
--
作者：
Jia HM;Li Q;Zhou C;Yu M;Yang Y;Zhang HW;Ding G;Shang H;Zou ZM
抑郁症是一种以一系列病理变化为特征的复杂疾病。抑郁症的研究主要集中在大脑的变化，而不是肝脏。因此，我们初步探讨了代谢谱的大鼠肝提取物治疗慢性不可预测的轻度应激（CNOMS）的UPLC-Q-TOF/MS。使用多变量统计分析，共26个改变代谢物区分CNOMS诱导的抑郁症从正常对照组被确定。采用两阶段受试者工作特征（ROC）分析，18种代谢物被认为是潜在的生物标志物，通过12个代谢途径与CNS诱导的抑郁症。随后，我们通过实时qRT-PCR检测了CUMS大鼠肝组织中Bax和Bcl-2等凋亡相关基因以及参与磷脂和初级胆汁酸生物合成的Pla 2g 15、Pnpla 6、Baat和Gad 1等四种关键酶的mRNA表达水平。Bax、Bcl-2、Pla 2g 15、Pnpla 6和Gad 1 mRNA表达水平分别是正常对照组的1.43、1.68、1.74、1.67和1.42倍，Baat、Bax/Bcl-2比值mRNA表达水平分别是正常对照组的0.83、0.85倍。肝脏靶向代谢组学和mRNA表达的结果表明，CNS诱导的抑郁症导致肝脏代谢谱和基因表达的变化，最终导致肝损伤。
Depression is a complex disease characterized by a series of pathological changes. Research on depression is mainly focused on the changes in brain, but not on liver. Therefore, we initially explored the metabolic profiles of hepatic extracts from rats treated with chronic unpredictive mild stress (CUMS) by UPLC-Q-TOF/MS. Using multivariate statistical analysis, a total of 26 altered metabolites distinguishing CUMS-induced depression from normal control were identified. Using two-stage receiver operating characteristic (ROC) analysis, 18 metabolites were recognized as potential biomarkers related to CUMS-induced depression via 12 metabolic pathways. Subsequently, we detected the mRNA expressions levels of apoptosis-associated genes such as Bax and Bcl-2 and four key enzymes including Pla2g15, Pnpla6, Baat and Gad1 involved in phospholipid and primary bile acid biosynthesis in liver tissues of CUMS rats by real-time qRT-PCR assay. The expression levels of Bax, Bcl-2, Pla2g15, Pnpla6 and Gad1 mRNA were 1.43,1.68, 1.74, 1.67 and 1.42-fold higher, and those of Baat, Bax/Bcl-2 ratio mRNA were 0.83, 0.85-fold lower in CUMS rats compared with normal control. Results of liver-targeted metabonomics and mRNA expression demonstrated that CUMS-induced depression leads to variations in hepatic metabolic profile and gene expression, and ultimately results in liver injury.