Boxiang Du1, Min Gao2, Liang Cao3, Jie Song1, Xueyin Shi4. 1. Department of Anesthesiology, The Second Affiliated Hospital of Nantong University Nantong, Jiangsu, China. 2. Department of Anesthesiology, The First Affiliated Hospital of Medical School of Zhejiang University Zhejiang, China. 3. Department of ICU, The Second Affiliated Hospital of Nantong University Nantong, Jiangsu, China. 4. Department of Anesthesiology and SICU, Xinhua Hospital, Shanghai Jiao Tong University Shanghai, China.
Abstract
OBJECTIVE: To investigate the expression of Notch signaling pathway after mechanical ventilation and its role in mechanical ventilation and lung injury. METHODS: VILI model was established by mechanical ventilation at high tidal volume (VT = 20 ml/kg) for 4 hours. Lung injury and inflammatory response were evaluated. Hes-1 and Hes-5 mRNA levels were measured after mechanical ventilation, and the levels of NICD, Hes-1, and Hes-5 protein were measured. Furthermore, the Notch signaling pathway inhibitor (DAPT 100 mg/kg) was administered intraperitoneally before mechanical ventilation to assess the role of Notch signaling in VILI. RESULTS: Compared with the control group, hypertonic mechanical ventilation induced VILI and increased the expression of inflammatory factors such as TNF-α, IL-6 and MIP-2 in the cell lavage fluid. The level of Hes-5 gene was significantly up-regulated in pulmonary macrophages with high tidal volume ventilation, and the protein levels of NICD and Hes-5 were up-regulated in pulmonary macrophages. The levels of TNF-α, IL-6, MIP-2 and other inflammatory cytokines in the alveolar lavage fluid decreased, and the levels of NICD and Hes-5 were also decreased, after DAPT pretreatment compared with the high tidal volume. The upregulation of p-IκBα and the degradation of IκBα protein in alveolar macrophages after mechanical ventilation was also observed. CONCLUSION: The expression of Notch signaling pathway protein in alveolar macrophages is upregulated after high tidal volume mechanical ventilation, and is involved in the regulation of mechanical ventilation and lung injury. Our results suggested that NF-κB pathway is likely involved in Notch-mediated mechanisms that underlie mechanical ventilation induced lung injury. IJCEP
OBJECTIVE: To investigate the expression of Notch signaling pathway after mechanical ventilation and its role in mechanical ventilation and lung injury. METHODS: VILI model was established by mechanical ventilation at high tidal volume (VT = 20 ml/kg) for 4 hours. Lung injury and inflammatory response were evaluated. Hes-1 and Hes-5 mRNA levels were measured after mechanical ventilation, and the levels of NICD, Hes-1, and Hes-5 protein were measured. Furthermore, the Notch signaling pathway inhibitor (DAPT 100 mg/kg) was administered intraperitoneally before mechanical ventilation to assess the role of Notch signaling in VILI. RESULTS: Compared with the control group, hypertonic mechanical ventilation induced VILI and increased the expression of inflammatory factors such as TNF-α, IL-6 and MIP-2 in the cell lavage fluid. The level of Hes-5 gene was significantly up-regulated in pulmonary macrophages with high tidal volume ventilation, and the protein levels of NICD and Hes-5 were up-regulated in pulmonary macrophages. The levels of TNF-α, IL-6, MIP-2 and other inflammatory cytokines in the alveolar lavage fluid decreased, and the levels of NICD and Hes-5 were also decreased, after DAPT pretreatment compared with the high tidal volume. The upregulation of p-IκBα and the degradation of IκBα protein in alveolar macrophages after mechanical ventilation was also observed. CONCLUSION: The expression of Notch signaling pathway protein in alveolar macrophages is upregulated after high tidal volume mechanical ventilation, and is involved in the regulation of mechanical ventilation and lung injury. Our results suggested that NF-κB pathway is likely involved in Notch-mediated mechanisms that underlie mechanical ventilation induced lung injury. IJCEP