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急性四肢瘫性肌病的猪模型:一项可行性研究。

A porcine model of acute quadriplegic myopathy: a feasibility study.

作者信息

Norman H, Kandala K, Kolluri R, Zackrisson H, Nordquist J, Walther S, Eriksson L I, Larsson L

机构信息

Department of Clinical Neurophysiology, Uppsala University, Sweden.

出版信息

Acta Anaesthesiol Scand. 2006 Oct;50(9):1058-67. doi: 10.1111/j.1399-6576.2006.01105.x. Epub 2006 Aug 25.

Abstract

BACKGROUND

The mechanisms underlying acute quadriplegic myopathy (AQM) are poorly understood, partly as a result of the fact that patients are generally diagnosed at a late stage of the disease. Accordingly, there is a need for relevant experimental animal models aimed at identifying underlying mechanisms.

METHODS

Pigs were mechanically ventilated and exposed to various combinations of agents, i.e. pharmacological neuromuscular blockade, corticosteroids and/or sepsis, for a period of 5 days. Electromyography and myofibrillar protein and mRNA expression were analysed using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), confocal microscopy, histochemistry and real-time polymerase chain reaction (PCR).

RESULTS

A decreased compound muscle action potential, normal motor nerve conduction velocities, and intact sensory nerve function were observed. Messenger RNA expression, determined by real-time PCR, of the myofibrillar proteins myosin and actin decreased in spinal and cranial nerve innervated muscles, suggesting that the loss of myosin observed in AQM patients is not solely the result of myofibrillar protein degradation.

CONCLUSION

The present porcine AQM model demonstrated findings largely in accordance with results previously reported in patients and offers a feasible approach to future mechanistic studies aimed at identifying underlying mechanisms and developing improved diagnostic tests and intervention strategies.

摘要

背景

急性四肢瘫性肌病(AQM)的潜在机制尚未完全明确,部分原因是患者通常在疾病晚期才被诊断出来。因此,需要建立相关实验动物模型以确定其潜在机制。

方法

对猪进行机械通气,并使其暴露于多种药物组合下,即药理学神经肌肉阻滞、皮质类固醇和/或脓毒症,持续5天。使用十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)、共聚焦显微镜、组织化学和实时聚合酶链反应(PCR)分析肌电图、肌原纤维蛋白及mRNA表达。

结果

观察到复合肌肉动作电位降低、运动神经传导速度正常以及感觉神经功能完好。通过实时PCR测定,在脊髓和脑神经支配的肌肉中,肌原纤维蛋白肌球蛋白和肌动蛋白的mRNA表达降低,这表明在AQM患者中观察到的肌球蛋白缺失并非仅由肌原纤维蛋白降解所致。

结论

目前的猪AQM模型所展示的结果在很大程度上与先前患者报告的结果一致,并为未来旨在确定潜在机制、开发改进的诊断测试和干预策略的机制研究提供了一种可行的方法。

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