PDF(Pubmed)
Abstract：
Mechanical ventilation (MV) is an essential life-saving technique, but prolonged MV can cause significant diaphragmatic dysfunction due to atrophy and decreased contractility of the diaphragm fibres, called ventilator-induced diaphragmatic dysfunction (VIDD). It is not clear about the mechanism of occurrence and prevention measures of VIDD. Irisin is a newly discovered muscle factor that regulates energy metabolism. Studies have shown that irisin can exhibit protective effects by downregulating endoplasmic reticulum (ER) stress in a variety of diseases; whether irisin plays a protective role in VIDD has not been reported. Sprague-Dawley rats were mechanically ventilated to construct a VIDD model, and intervention was performed by intravenous administration of irisin. Diaphragm contractility, degree of atrophy, cross-sectional areas (CSAs), ER stress markers, AMPK protein expression, oxidative stress indicators and apoptotic cell levels were measured at the end of the experiment.Our findings showed that as the duration of ventilation increased, the more severe the VIDD was, the degree of ER stress increased, and the expression of irisin decreased.ER stress may be one of the causes of VIDD. Intervention with irisin ameliorated VIDD by reducing the degree of ER stress, attenuating oxidative stress, and decreasing the apoptotic index. MV decreases the expression of phosphorylated AMPK in the diaphragm, whereas the use of irisin increases the expression of phosphorylated AMPK. Irisin may exert its protective effect by activating the phosphorylated AMPK pathway.
摘要：
机械通气（MV）是一种必不可少的救命技术，但长时间的MV会导致严重的膈肌功能障碍，由于萎缩和膈肌纤维的收缩性下降，称为呼吸机诱发的膈肌功能障碍（VIDD）。VIDD的发生机制和预防措施尚不清楚。Irisin是一种新发现的调节能量代谢的肌肉因子。研究表明，irisin可通过下调内质网（ER）应激在多种疾病中发挥保护作用；irisin是否在VIDD中起保护作用尚未见报道。Sprague-Dawley大鼠机械通气构建VIDD模型,通过静脉注射irisin进行干预.膈肌收缩性,萎缩程度,横截面积(CSA)，ER应力标记,AMPK蛋白表达,在实验结束时测量氧化应激指标和凋亡细胞水平。我们的研究结果表明，随着通风时间的增加，视频越严重，ER应力程度增加，irisin的表达下降。ER应激可能是VIDD的原因之一。用irisin干预通过降低ER应激程度改善VIDD，减弱氧化应激，并降低凋亡指数。MV降低膈肌磷酸化AMPK的表达，而使用irisin会增加磷酸化AMPK的表达。Irisin可能通过激活磷酸化的AMPK途径发挥其保护作用。
