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健康妊娠母马和实验性诱导胎膜炎母马的血浆代谢组学分析。

Plasma metabolomic profiling of healthy pregnant mares and mares with experimentally induced placentitis.

机构信息

College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USA.

Department of Biochemistry, North Carolina State University, Raleigh, NC, USA.

出版信息

Equine Vet J. 2021 Jan;53(1):85-93. doi: 10.1111/evj.13262. Epub 2020 Apr 15.

Abstract

BACKGROUND

Metabolomics may represent an avenue for diagnosis of equine ascending placentitis.

OBJECTIVES

To characterise the plasma metabolomic profile in healthy mares and mares with induced ascending placentitis, with the goal of identifying metabolites with potential clinical value for early diagnosis of placentitis.

STUDY DESIGN

Controlled in vivo experiment.

METHODS

Placentitis was induced in 10 late-term pregnant pony mares via Streptococcal equi subsp. zooepidemicus inoculation in five mares between days 285 and 290 of gestation, while five mares served as healthy controls. Repeated ultrasound examinations and jugular venipuncture were performed to obtain combined thickness of the uterus and placenta (CTUP) and plasma for NMR spectroscopy. Mares with increased CTUP were diagnosed with placentitis and treated in accordance with published therapeutic recommendations. NMR metabolomic analysis was performed to identify and quantify plasma metabolites at each time point. Concentrations were compared using ANOVA with repeated-measures and PLS-DA analysis.

RESULTS

Four hours post-inoculation, a significant increase was detected in the metabolites alanine, phenylalanine, histidine, pyruvate, citrate, glucose, creatine, glycolate, lactate and 3-hydroxyisobutyrate that returned to baseline by 12 hours. On day 4, a significant reduction in the metabolites alanine, phenylalanine, histidine, tyrosine, pyruvate, citrate, glycolate, lactate and dimethylsulfone was seen in infected mares compared with controls.

MAIN LIMITATIONS

There were small numbers of mares within groups. In addition, this work compares healthy animals with animals treated with multimodal therapeutics following diagnosis of placentitis without an untreated cohort.

CONCLUSIONS

Two phases of metabolite changes were noted after experimental infection: An immediate rise in metabolite concentration involved in energy, nitrogen, hydrogen and oxygen metabolism within 4 hours after inoculation that was followed by a decrease in metabolite concentrations involved in energy and nitrogen metabolism at 4 days, coinciding with ultrasonographic diagnosis of placentitis.

摘要

背景

代谢组学可能为马属动物上行性胎膜炎的诊断提供新途径。

目的

描述健康妊娠母马和诱导上行性胎膜炎母马的血浆代谢组特征,旨在确定具有早期诊断胎膜炎潜在临床价值的代谢物。

研究设计

体内对照实验。

方法

5 匹妊娠晚期的小型马在妊娠第 285 至 290 天接种马链球菌兽疫亚种,诱发胎膜炎,另 5 匹作为健康对照。通过重复超声检查和颈静脉采血获得子宫和胎盘总厚度(CTUP)和用于 NMR 光谱分析的血浆。CTUP 增加的母马被诊断为胎膜炎,并根据已发表的治疗建议进行治疗。在每个时间点进行 NMR 代谢组分析以鉴定和定量血浆代谢物。采用重复测量方差分析和 PLS-DA 分析比较浓度。

结果

接种后 4 小时,检测到代谢物丙氨酸、苯丙氨酸、组氨酸、丙酮酸、柠檬酸、葡萄糖、肌酸、乙醇酸、乳酸和 3-羟基异丁酸的浓度显著增加,12 小时后恢复基线。第 4 天,与对照组相比,感染母马的代谢物丙氨酸、苯丙氨酸、组氨酸、酪氨酸、丙酮酸、柠檬酸、乙醇酸、乳酸和二甲亚砜的浓度显著降低。

主要局限性

每组马的数量较少。此外,本研究比较了诊断为胎膜炎后接受多模式治疗的健康动物与未接受治疗的动物,而没有与未患病动物进行比较。

结论

在实验感染后观察到代谢物变化的两个阶段:接种后 4 小时内,能量、氮、氢和氧代谢相关的代谢物浓度立即升高,随后在第 4 天,能量和氮代谢相关的代谢物浓度下降,与超声诊断胎膜炎一致。

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