Abstract
Acute lung injury (ALI) is a common critical respiratory disease that seriously threatens human health. Ketamine has good anti-inflammatory and immune-regulating properties that can delay the lung injury process. High mobility group box protein 1 (HMGB1) plays an important role in the occurrence, development and treatment of ALI. Toll-like receptor 4 (TLR4) is the receptor for HMGB1. The aim of this study was to determine the role of the HMGB1 TLR4 signaling pathway in the treatment of ALI using ketamine. A total of 30 healthy, male, 8-week-old Sprague-Dawley rats were randomly, equally divided into a control group, an lipopolysaccharide (LPS) group and a ketamine group. In order to establish a rat ALI model, 15 mg/kg of LPS was injected into the femoral veins. Ketamine was intravenously injected (10 mg/kg) into the experimental group rats. The rats were euthanized 24 h after modeling and lung tissue samples were collected. Western blot was used to test TLR4, MyD88, TRAF-6, LOX-1, and HMGB1 protein expression in the lung tissue. Real-time polymerase chain reaction (RT-PCR) was performed to detect TLR4, MyD88, TRAF-6, LOX-1, and HMGB1 mRNA levels. Compared with the controls, the LPS group had significantly higher TLR4, MyD88, TRAF-6, LOX-1, and HMGB1 mRNA and protein levels (p < 0.05). These levels were significantly lower after ketamine intervention in comparison with the LPS group (p < 0.05). A positive correlation was found between TLR4 and HMGB1 expression in the LPS and ketamine groups (r = 0.952, p < 0.001; r = 0.941, p < 0.001). Ketamine attenuates HMGB1-induced ALI, possibly by regulating the TLR4 signaling pathway.
Highlights
Acute lung injury (ALI) is a type of pulmonary inflammatory reaction which is caused by severe trauma, shock, severe infections, acidosis, and injuries of capillary endothelial cells and alveolar epithelial cells triggered by inflammatory cell cascade.[1]
A positive correlation was found between Toll-like receptor 4 (TLR4) and High mobility group box protein 1 (HMGB1) expression in the LPS and ketamine groups (r = 0.952, p < 0.001; r = 0.941, p < 0.001)
Western blot analysis was performed to detect TLR4, MyD88, TRAF-6, LOX-1, and HMGB1 protein levels, and the findings demonstrate a similar tendency as with mRNA (Table 2 and Fig. 2)
Summary
Acute lung injury (ALI) is a type of pulmonary inflammatory reaction which is caused by severe trauma, shock, severe infections, acidosis, and injuries of capillary endothelial cells and alveolar epithelial cells triggered by inflammatory cell cascade.[1]. Acute lung injury may advance to acute respiratory distress syndrome. It is a common critical disease featuring rapid onset, quick development, poor prognosis, and high mortality.[2]. Ketamine is widely used in clinical intravenous anesthesia. It has anti-inflammatory and immune-regulating functions, and presents a great inhibitory effect which prevents the production of a variety of inflammatory cytokines, the function of neutrophils and the expression of adhesion molecule.[4–6]. A previous study demonstrated that ketamine can improve the blood gas and pulmonary function index of patients with ALI caused by mechanical ventilation.[9]. Acute lung injury (ALI) is a common critical respiratory disease that seriously threatens human health. Ketamine has good anti-inflammatory and immune-regulating properties that can delay the lung injury process
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