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使用超极化磁共振波谱对糖尿病大鼠心脏和肝脏代谢进行同步体内评估。

Simultaneous in vivo assessment of cardiac and hepatic metabolism in the diabetic rat using hyperpolarized MRS.

作者信息

Le Page Lydia M, Ball Daniel R, Ball Vicky, Dodd Michael S, Miller Jack J, Heather Lisa C, Tyler Damian J

机构信息

Cardiac Metabolism Research Group, Department of Physiology Anatomy and Genetics, University of Oxford, Oxford, UK.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.

出版信息

NMR Biomed. 2016 Dec;29(12):1759-1767. doi: 10.1002/nbm.3656. Epub 2016 Oct 25.

Abstract

Understanding and assessing diabetic metabolism is vital for monitoring disease progression and improving treatment of patients. In vivo assessments, using MRI and MRS, provide non-invasive and accurate measurements, and the development of hyperpolarized C spectroscopy in particular has been demonstrated to provide valuable metabolic data in real time. Until now, studies have focussed on individual organs. However, diabetes is a systemic disease affecting multiple tissues in the body. Therefore, we have developed a technique to simultaneously measure metabolism in both the heart and liver during a single acquisition. A hyperpolarized C MRS protocol was developed to allow acquisition of metabolic data from the heart and liver during a single scan. This protocol was subsequently used to assess metabolism in the heart and liver of seven control male Wistar rats and seven diabetic rats (diabetes was induced by three weeks of high-fat feeding and a 30 mg/kg injection of streptozotocin). Using our new acquisition, we observed decreased cardiac and hepatic pyruvate dehydrogenase flux in our diabetic rat model. These diabetic rats also had increased blood glucose levels, decreased insulin, and increased hepatic triglycerides. Decreased production of hepatic [1- C]alanine was observed in the diabetic group, but this change was not present in the hearts of the same diabetic animals. We have demonstrated the ability to measure cardiac and hepatic metabolism simultaneously, with sufficient sensitivity to detect metabolic alterations in both organs. Further, we have non-invasively observed the different reactions of the heart and liver to the metabolic challenge of diabetes.

摘要

了解和评估糖尿病代谢对于监测疾病进展和改善患者治疗至关重要。使用MRI和MRS进行的体内评估可提供非侵入性且准确的测量,特别是超极化碳谱的发展已被证明能实时提供有价值的代谢数据。到目前为止,研究主要集中在单个器官上。然而,糖尿病是一种影响身体多个组织的全身性疾病。因此,我们开发了一种技术,能够在一次采集过程中同时测量心脏和肝脏的代谢情况。我们制定了一种超极化碳MRS方案,以便在单次扫描期间获取心脏和肝脏的代谢数据。随后,该方案被用于评估7只对照雄性Wistar大鼠和7只糖尿病大鼠(通过三周高脂喂养和注射30mg/kg链脲佐菌素诱导糖尿病)心脏和肝脏的代谢情况。通过我们新的采集方法,我们观察到在糖尿病大鼠模型中心脏和肝脏的丙酮酸脱氢酶通量降低。这些糖尿病大鼠还出现血糖水平升高、胰岛素降低以及肝脏甘油三酯增加的情况。在糖尿病组中观察到肝脏[1-碳]丙氨酸生成减少,但在相同糖尿病动物的心脏中未出现这种变化。我们已经证明了同时测量心脏和肝脏代谢的能力,并且具有足够的灵敏度来检测两个器官中的代谢改变。此外,我们还非侵入性地观察到了心脏和肝脏对糖尿病代谢挑战的不同反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/710a/5132204/5e57665e729d/NBM-29-1759-g001.jpg

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