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评估左旋肉碱对斑马鱼模型他汀类药物后肌肉损伤的预防作用。

Assessment of the Preventive Effect of L-carnitine on Post-statin Muscle Damage in a Zebrafish Model.

机构信息

Hirszfeld Institute of Immunology and Experimental Therapy, The Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wroclaw, Poland.

Department of Animal Developmental Biology, University of Wrocław, Sienkiewicza 21, 50-335 Wroclaw, Poland.

出版信息

Cells. 2022 Apr 11;11(8):1297. doi: 10.3390/cells11081297.

Abstract

Statins, such as lovastatin, are lipid-lowering drugs (LLDs) that have been used to treat hypercholesterolaemia, defined as abnormally elevated cholesterol levels in the patient's blood. Although statins are considered relatively safe and well tolerated, recipients may suffer from adverse effects, including post-statin myopathies. Many studies have shown that supplementation with various compounds may be beneficial for the prevention or treatment of side effects in patients undergoing statin therapy. In our study, we investigated whether L-carnitine administered to zebrafish larvae treated with lovastatin alleviates post-statin muscle damage. We found that exposure of zebrafish larvae to lovastatin caused skeletal muscle disruption observed as a reduction of birefringence, changes in muscle ultrastructure, and an increase in atrogin-1. Lovastatin also affected heart performance and swimming behaviour of larvae. Our data indicated that the muscle-protective effect of L-carnitine is partial. Some observed myotoxic effects, such as disruption of skeletal muscle and increase in atrogin-1 expression, heart contraction could be rescued by the addition of L-carnitine. Others, such as slowed heart rate and reduced locomotion, could not be mitigated by L-carnitine supplementation.

摘要

他汀类药物,如洛伐他汀,是降脂药物(LLD),用于治疗高胆固醇血症,定义为患者血液中胆固醇水平异常升高。虽然他汀类药物被认为相对安全且耐受良好,但接受者可能会出现不良反应,包括他汀类药物引起的肌肉疾病。许多研究表明,补充各种化合物可能有益于预防或治疗接受他汀类药物治疗的患者的副作用。在我们的研究中,我们研究了给予洛伐他汀处理的斑马鱼幼虫的左旋肉碱是否缓解了他汀类药物引起的肌肉损伤。我们发现,洛伐他汀暴露于斑马鱼幼虫中会导致骨骼肌破坏,表现为双折射减少、肌肉超微结构改变和肌萎缩蛋白-1 增加。洛伐他汀还影响幼虫的心脏功能和游泳行为。我们的数据表明,左旋肉碱的肌肉保护作用是部分的。一些观察到的肌肉毒性作用,如骨骼肌破坏和肌萎缩蛋白-1 表达增加,可以通过添加左旋肉碱来挽救。其他作用,如心率减慢和运动减少,不能通过左旋肉碱补充来减轻。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9a2e/9032104/fbba1be9bbde/cells-11-01297-g001.jpg

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