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中风会引起小鼠脂质代谢、肝脏和身体成分的长期变化。

Stroke Induces Prolonged Changes in Lipid Metabolism, the Liver and Body Composition in Mice.

机构信息

Division of Neuroscience and Experimental Psychology and Lydia Becker Institute of Immunology and Inflammation, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, M13 9PT, UK.

出版信息

Transl Stroke Res. 2020 Aug;11(4):837-850. doi: 10.1007/s12975-019-00763-2. Epub 2019 Dec 21.

Abstract

During recovery, stroke patients are at risk of developing long-term complications that impact quality of life, including changes in body weight and composition, depression and anxiety, as well as an increased risk of subsequent vascular events. The aetiologies and time-course of these post-stroke complications have not been extensively studied and are poorly understood. Therefore, we assessed long-term changes in body composition, metabolic markers and behaviour after middle cerebral artery occlusion in mice. These outcomes were also studied in the context of obesity, a common stroke co-morbidity proposed to protect against post-stroke weight loss in patients. We found that stroke induced long-term changes in body composition, characterised by a sustained loss of fat mass with a recovery of lean weight loss. These global changes in response to stroke were accompanied by an altered lipid profile (increased plasma free fatty acids and triglycerides) and increased adipokine release at 60 days. After stroke, the liver also showed histological changes indicative of liver damage and a decrease in plasma alanine aminotransferase (ALT) was observed. Stroke induced depression and anxiety-like behaviours in mice, illustrated by deficits in exploration, nest building and burrowing behaviours. When initial infarct volumes were matched between mice with and without comorbid obesity, these outcomes were not drastically altered. Overall, we found that stroke induced long-term changes in depressive/anxiety-like behaviours, and changes in plasma lipids, adipokines and the liver that may impact negatively on future vascular health.

摘要

在恢复期间,中风患者有发生长期并发症的风险,这些并发症会影响生活质量,包括体重和身体成分的变化、抑郁和焦虑,以及随后发生血管事件的风险增加。这些中风后并发症的病因和时间进程尚未得到广泛研究,也了解甚少。因此,我们评估了大脑中动脉闭塞后小鼠的身体成分、代谢标志物和行为的长期变化。在肥胖的背景下也研究了这些结果,肥胖是一种常见的中风合并症,据推测它可以预防中风患者的体重减轻。我们发现,中风会导致身体成分的长期变化,其特征是脂肪量持续减少,瘦体重恢复。这些对中风的全身性反应伴随着脂质谱的改变(血浆游离脂肪酸和甘油三酯增加)和 60 天后脂肪因子释放增加。中风后,肝脏也显示出肝损伤的组织学变化,并且观察到血浆丙氨酸氨基转移酶(ALT)的减少。中风会引起小鼠的抑郁和焦虑样行为,表现为探索、筑巢和挖掘行为的缺陷。当肥胖伴发和不伴发肥胖的小鼠的初始梗死体积相匹配时,这些结果并没有发生巨大改变。总的来说,我们发现中风会引起抑郁/焦虑样行为的长期变化,以及血浆脂质、脂肪因子和肝脏的变化,这可能对未来的血管健康产生负面影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03d5/7340675/5acb7fbf52c7/12975_2019_763_Fig1_HTML.jpg

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