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在动物模型(金黄仓鼠,Mesocricetus auratus)中对肝片形吸虫感染的时间分辨反应的血浆代谢组学。

Plasma metabolomics of the time resolved response to Opisthorchis felineus infection in an animal model (golden hamster, Mesocricetus auratus).

机构信息

Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.

Laboratory of clinical metabolomics, Tomsk State University, Tomsk, Russia.

出版信息

PLoS Negl Trop Dis. 2020 Jan 24;14(1):e0008015. doi: 10.1371/journal.pntd.0008015. eCollection 2020 Jan.

Abstract

BACKGROUND

Opisthorchiasis is a hepatobiliary disease caused by flukes of the trematode family Opisthorchiidae. Opisthorchiasis can lead to severe hepatobiliary morbidity and is classified as a carcinogenic agent. Here we investigate the time-resolved metabolic response to Opisthorchis felineus infection in an animal model.

METHODOLOGY

Thirty golden hamsters were divided in three groups: severe infection (50 metacercariae/hamster), mild infection (15 metacercariae/hamster) and uninfected (vehicle-PBS) groups. Each group consisted of equal number of male and female animals. Plasma samples were collected one day before the infection and then every two weeks up to week 22 after infection. The samples were subjected to 1H Nuclear Magnetic Resonance (NMR) spectroscopy and multivariate statistical modelling.

PRINCIPAL FINDINGS

The time-resolved study of the metabolic response to Opisthorchis infection in plasma in the main lines agrees with our previous report on urine data. The response reaches its peak around the 4th week of infection and stabilizes after the 10th week. Yet, unlike the urinary data there is no strong effect of the gender in the data and the intensity of infection is presented in the first two principal components of the PCA model. The main trends of the metabolic response to the infection in blood plasma are the transient depletion of essential amino acids and an increase in lipoprotein and cholesterol concentrations.

CONCLUSIONS

The time resolved metabolic signature of Opisthorchis infection in the hamster's plasma shows a coherent shift in amino acids and lipid metabolism. Our work provides insight into the metabolic basis of the host response on the helminth infection.

摘要

背景

华支睾吸虫病是一种由复殖目华支睾科吸虫引起的肝胆疾病。华支睾吸虫病可导致严重的肝胆疾病,并被归类为致癌物质。在这里,我们研究了在动物模型中对华支睾吸虫感染的时间分辨代谢反应。

方法

将 30 只金黄地鼠分为三组:重度感染组(50 尾囊蚴/地鼠)、轻度感染组(15 尾囊蚴/地鼠)和未感染组(载体-PBS)。每组由数量相等的雄性和雌性动物组成。在感染前一天采集血浆样本,然后每两周采集一次,直至感染后第 22 周。将样本进行 1H 核磁共振(NMR)光谱和多变量统计建模。

主要发现

对华支睾吸虫感染在血浆中代谢反应的时间分辨研究与我们之前关于尿液数据的报告一致。感染后第 4 周左右达到峰值,第 10 周后稳定。然而,与尿液数据不同的是,数据中没有性别因素的强烈影响,感染强度体现在 PCA 模型的前两个主成分中。感染对血液代谢反应的主要趋势是必需氨基酸的短暂消耗,以及脂蛋白和胆固醇浓度的增加。

结论

华支睾吸虫感染在仓鼠血浆中的时间分辨代谢特征显示出氨基酸和脂质代谢的一致变化。我们的工作为宿主对寄生虫感染的代谢基础提供了深入了解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b736/7002010/b241579fa5b1/pntd.0008015.g001.jpg

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