Liu Pei, Zhang Hongmei, Hu Ke, Zheng Hongmei
Division of Respiratory Disease, Renmin Hospital of Wuhan University Wuhan 430060, Hubei Province, P. R. C.
Department of Respiratory Disease, Taihe Hospital, Hubei University of Medicine Hubei, P. R. C.
Int J Clin Exp Pathol. 2017 Aug 1;10(8):8515-8519. eCollection 2017.
Inflammation is involved in ventilator-induced diaphragm dysfunction. Toll-like receptor 4 (TLR4) is an important inflammatory factor, but it remains unclear whether TLR4 contributes to ventilator-induced diaphragm dysfunction. This study aimed to investigate the role of TLR4 signaling in ventilator-induced diaphragm dysfunction. Total 30 adult male SD rats were randomly divided into control group, low tidal volume and high tidal volume group (n = 10). Control group received tracheotomy and endotracheal intubation but no mechanical ventilation; low tidal volume group and high tidal volume group received tracheotomy, mechanical ventilation after intubation, and then received tidal volume 6 ml/kg and 20 ml/kg, respectively. Ventilation rate was 60 beats/min, inspiratory to expiratory ratio was 1:3, FiO was 21%, ventilation was 24 h. Diaphragmatic muscle contraction, tumor necrosis factor (TNF-α) and TLR4 expression, and malondialdehyde (MDA) and superoxide dismutase (SOD) contents in the diaphragm tissues were detected. TLR4 and TNF-α expression in diaphragm tissues of high tidal volume group were significantly increased and diaphragm muscle contraction was significantly decreased, compared to other groups. In conclusion, high tidal volume ventilation may activate TLR4 signaling and cause pathological changes in diaphragm tissues. TLR4 is a promising target for the prevention and treatment of ventilator-associated diaphragmatic injury.
炎症参与呼吸机诱发的膈肌功能障碍。Toll样受体4（TLR4）是一种重要的炎症因子，但TLR4是否导致呼吸机诱发的膈肌功能障碍仍不清楚。本研究旨在探讨TLR4信号通路在呼吸机诱发的膈肌功能障碍中的作用。将30只成年雄性SD大鼠随机分为对照组、低潮气量组和高潮气量组（n = 10）。对照组行气管切开和气管插管，但不进行机械通气；低潮气量组和高潮气量组行气管切开、插管后机械通气，然后分别给予6 ml/kg和20 ml/kg的潮气量。通气频率为60次/分钟，吸呼比为1:3，FiO为21%，通气24小时。检测膈肌收缩、肿瘤坏死因子（TNF-α）和TLR4表达，以及膈肌组织中丙二醛（MDA）和超氧化物歧化酶（SOD）含量。与其他组相比，高潮气量组膈肌组织中TLR4和TNF-α表达显著增加，膈肌收缩显著降低。综上所述，高潮气量通气可能激活TLR4信号通路并导致膈肌组织发生病理变化。TLR4是预防和治疗呼吸机相关性膈肌损伤的一个有前景的靶点。
