【摘要】 目的 探讨产前应激(PS)对子代大鼠心脏代谢物轮廓变化的影响，分析关键差异信号通路中关键差异物的潜在作用。方法 构建产前束缚应激大鼠模型(PS组),采用UHPLC-Q-TOF/MS分析法检测对照组和PS组子代大鼠心脏组织中代谢物轮廓的变化，通过KEGG通路注释与分析，筛选出关键信号通路的代谢差异物并定量其表达水平，进而推测这些关键分子影响PS对子代大鼠心脏组织的潜在作用。结果 与对照组相比，PS组子代大鼠心脏组织中显著变化的信号通路包括氨基酸的生物合成、嘌呤代谢、嘧啶代谢、丙氨酸/天冬氨酸盐和谷氨酸代谢、cAMP信号通路、精氨酸的生物合成、GABA能突触、谷氨酸能突触、尼古丁成瘾和肌动蛋白细胞骨架调节。其中富集在嘌呤代谢、嘧啶代谢和精氨酸的生物合成通路中的L-谷氨酰胺、假尿嘧啶、尿酸、黄嘌呤、2′-脱氧腺苷5′-单磷酸、胞氨酸3′-单磷酸、胞氨酸5′-单磷酸水平显著上调，精氨琥珀酸水平显著下调。结论 PS导致子代大鼠心脏组织中L-谷氨酰胺、假尿嘧啶、尿酸、黄嘌呤异常变化，PS可能是子代大鼠心血管疾病发病的高危因素。更多还原

【Abstract】 Objective To investigate the effect of prenatal stress(PS) on the profile changes of cardiac metabolites in offspring rats and to analyze the potential role of key differentiators in key differential signaling pathways. Methods UHPLC-Q-TOF/MS analysis was used to detect the changes of metabolite profile in the heart tissues of offspring rats in control group and PS group. KEGG pathway annotation and analysis were used to screen out metabolic differences in key signaling pathways and quantify their expression levels so as to predict the potential function of these key molecules in the effect of PS on the heart tissues of offspring rats. Results Compared with the control group rats, the signaling pathways in the PS offspring rats’ heart tissue that changed significantly included biosynthesis of amino acids, purine metabolism, pyrimidine metabolism, alanine, aspartate and glutamate metabolism, cAMP signaling pathways, arginine biosynthesis, GABAergic synapses, glutamate synapse, nicotine addiction, and regulation of actin cytoskeleton. Among them, the levels of L-glutamine, pseuduracil, uric acid, xanthine, 2’-deoxyadenosine 5’-monophosphate, cytosine 3’-monophosphate, and cytosine 5’-monophosphate were upregulated, while the level of argininosuccinic acid was downregulated, which enriched in purine metabolism, pyrimidine metabolism, and arginine biosynthesis pathway. Conclusion PS leads to abnormal changes of L-glutamine, pseuduracil, uric acid, and xanthine in the heart tissue of offspring rats, and PS may be a high risk factor for cardiovascular diseases in offspring rats.更多还原