Effect of incubation with lipopolysaccharide and interferon-γ on reactive astrogliosis.

Sepsis associated encephalopathy is a common complication of sepsis, but its pathogenesis of sepsis-associated encephalopathy remains unclear. Astrocytes are the most abundant brain glial cells, and reactive astrogliosis, a pathological response to central nervous system diseases, has a clear disease and disease-stage specificity. Functional changes of astrocytes are of great significance for the detection and prognosis of sepsis-associated encephalopathy. The pathogenesis of sepsis-associated encephalopathy was explored at the cellular level by examining astrogliosis in an in vitro model of sepsis-associated encephalopathy. Astrocytes of Wistar neonatal rats were incubated with different concentrations of lipopolysaccharide combined with interferon-γ. Cell viability was assessed by levels of tumor necrosis factor-α, interleukin-6, nitric oxide, reactive oxygen species, glial fibrillary acidic protein, changes of astrocyte morphology, and prevalence of apoptosis and necrosis. Compared with the control group, the cell viability of treated groups was decreased. The levels of tumor necrosis factor-α, interleukin-6, nitric oxide, reactive oxygen species, and glial fibrillary acidic protein were increased, hypertrophy of astrocytes was observed, and apoptosis was increased. The pathogenic outcomes of astrogliosis in sepsis-associated encephalopathy is discussed and a new tool provided to explore the pathogenesis of sepsis-associated encephalopathy at the cellular level.

PTX3 Protects Intestinal Mucosal Barrier Damage in Sepsis Through Toll-Like Receptor Signaling Pathway.

This study aims to confirm the protective effect of Pentraxin 3 (PTX3) on intestinal mucosal barrier damage in sepsis in animal and cell models and explore its mechanism. Analysis of the GSE147775 gene set revealed that the level of PTX3 was upregulated in the lipopolysaccharide (LPS)-induced rat sepsis model. The mice sepsis model was established by cecal ligation perforation (CLP), and the cell inflammation model was induced by LPS. Cell apoptosis and the expression of apoptosis-related protein were detected by flow cytometry and Western blotting. The PTX3 level was significantly upregulated in the mice sepsis model. Intestinal mucosal barrier damage was aggravated and inflammatory factor expression was upregulated after PTX3 downregulation in sepsis mice. After upregulation of PTX3, intestinal mucosal barrier damage was alleviated and inflammatory factor expression was decreased in sepsis mice. Further data mining suggested that the anti-inflammatory effect of PTX3 might be realized through inhibition of the toll-like receptor (TLR) signaling pathway. Moreover, compared with the LPS group, downregulation of PTX3 increased cell apoptosis and the levels of BCL2-associated X (Bax), myeloperoxidase (MPO), tumor necrosis factor-alfa (TNF-α), interleukin 1 beta (IL-1ß), and interferon-gamma (IFN-γ), and decreased the levels of B-cell lymphoma-2 (Bcl-2), zona occludens (ZO)-1, and occludin. On the contrary, overexpression of PTX3 reduced cell apoptosis and the levels of Bax, MPO, TNF-α, IL-1ß, and IFN-γ. Moreover, downregulation of PTX3 reversed the inhibitive effects on cell apoptosis and inflammation and promotive effects on the levels of Zo-1 and occludin induced by CLI-095 (a TLR signaling pathway inhibitor). In the CLP-induced mice sepsis model and LPS-induced cell inflammation model, PTX3 inhibits inflammatory response and reduces intestinal mucosal barrier damage through the TLR signaling pathway.

[The study of AutoFlow role in volume controlled ventilation].

OBJECTIVE: To evaluate the efficacy and safety of automatic variable flow rate (AutoFlow) for volume control ventilation through monitoring the number of ventilator alarm. METHODS: Forty-eight adult patients receiving the Drager Evita 4 ventilator with an expectation of more than 2 days duration were divided into two groups by randomly digital methods, each n=24. The patients in control group were received routinely mode with synchronized intermittent mandatory ventilation (SIMV), and the others in observation group were given SIMV and assist with AutoFlow. The midazolam and fentanyl was given to retain the Ramsay score 2-3 by continuous micro-pump. The ventilator alarm, blood gas analysis and respiratory function were recorded. RESULTS: There were no significant differences in respiratory rate (RR), tidal volume (VT), positive end-expiratory pressure (PEEP), fraction of inspired oxygen (FiO2), pH, arterial partial pressure of carbon dioxide (PaCO2), arterial partial pressure of oxygen (PaO2), oxygenation index (PaO2/FiO2), as well as sedative dose and time between two groups within 5 days of mechanical ventilation. Duration of mechanical ventilation in all patients was 164 days (3756 hours), and 78 days (1812 hours) in control group, 86 days (1944 hours) in observation group. The duration of mechanical ventilation in observation group was longer than that in control group [3 (1-15) days vs. 2 (1-28) days, P>0.05]. A total of 23 843 alarms were recorded, approximately 6 times/h, and 17 386 alarms in control group, averagely 9.6 times/h, 6457 alarms in the observation group, averagely 3.3 times/h. The number of ventilator alarm in observation group was less than that in control group (P<0.01). The number of airway pressure alarm in observation group was less than that in the control group [122 (8-1068) vs. 565 (13-1898), P<0.01]. There was no significant difference in sequential organ failure assessment (SOFA) score within 5 days between the two sets of mechanical ventilation. In the observation group ventilator-associated pneumonia (VAP) was occurred in 4 cases, and no pneumothorax happened, while in the control group there were 8 cases and 2 cases respectively. The mortality rate in intensive care unit (ICU) in observation group was lower than that in control group, but there was no statistical difference (25.0% vs. 37.5%, P>0.05). CONCLUSIONS: AutoFlow is confirmed be safe for volume control ventilation mode, and could significantly reduce the alarm of ventilator.