Electrical Stimulation Mitigates Muscle Degradation Shift in Gene Expressions during 12-hour Mechanical Ventilation

Ventilator-induced diaphragm dysfunction (VIDD), a dysfunction of the diaphragm muscle caused by prolonged mechanical ventilation (MV), is an important factor that hinders successful weaning from ventilation. We evaluated the effects of electrical stimulation of the diaphragm muscle (pulsed current with off-time intervals) on genetic changes during 12 hours of MV (E-V12). Rats were divided into four groups: control, 12-hour MV, sham operation, and E-V12 groups. Transcriptome analysis using an RNA microarray revealed that 12-hour MV caused upregulation of genes promoting muscle atrophy and downregulation of genes facilitating muscle synthesis, suggesting that 12-hour MV is a reasonable method for establishing a VIDD rat model. Of the genes upregulated by 12-hour MV, 18 genes were not affected by the sham operation but were downregulated by E-V12. These included genes related to catabolic processes, inflammatory cytokines, and skeletal muscle homeostasis. Of the genes downregulated by 12-hour MV, 6 genes were not affected by the sham operation but were upregulated by E-V12. These included genes related to oxygen transport and mitochondrial respiration. These results suggested that 12-hour MV shifted gene expression in the diaphragm muscle toward muscle degradation and that electrical stimulation counteracted this shift by suppressing catabolic processes and increasing mitochondrial respiration.呼吸机诱导的膈肌功能障碍（Ventilator-induced diaphragm dysfunction, VIDD）是指由长时间机械通气（Mechanical Ventilation, MV）引发的膈肌功能异常，是阻碍机械通气顺利脱机的重要危险因素。本研究评估了采用带间歇时间的脉冲电流的膈肌电刺激，对12小时机械通气（E-V12）过程中基因表达变化的影响。实验将大鼠分为四组：对照组、12小时机械通气组、假手术组与E-V12组。通过RNA微阵列开展转录组分析后发现，12小时机械通气可上调促肌肉萎缩基因的表达，并下调促肌肉合成基因的表达，提示12小时机械通气是建立VIDD大鼠模型的合理方法。在12小时机械通气上调的基因中，有18个基因不受假手术操作影响，但可被E-V12下调，这些基因涉及分解代谢过程、炎症细胞因子及骨骼肌稳态相关通路。在12小时机械通气下调的基因中，有6个基因不受假手术操作影响，但可被E-V12上调，这些基因涉及氧转运与线粒体呼吸相关通路。上述结果表明，12小时机械通气可使膈肌的基因表达向肌肉降解方向偏移，而电刺激可通过抑制分解代谢过程、增强线粒体呼吸来抵消这一异常偏移。