ABSTRACT
Objective:To evaluate the role of aryl hydrocarbon receptor (AhR) in the down-regulation of Clara cell secretory protein (CCSP) expression during endotoxin-induced lung injury in rats.Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 8 weeks, weighing 200-250 g, were divided into 4 groups ( n=6 each) using a random number table method: normal control group (group C), acute lung injury (ALI) group, ALI+ AhR antagonist group, and ALI+ vehicle group. Lipopolysaccharide(LPS) 1 mg/kg was intratracheally instilled to develop the model of lung injury, while the equal volume of normal saline was given instead in group C. At 2 h before LPS injection, AhR antagonist 6, 2′, 4′-trimethoxyflavone solution 5 mg/kg (diluted to 1 ml in dimethyl sulfoxide solution) was intraperitoneally injected in ALI+ AhR antagonist group, while dimethyl sulfoxide solution 1 ml was given in ALI+ vehicle group. The rats were sacrificed under anesthesia at 48 h after LPS administration. The left lung was lavaged and the broncho-alveolar lavage fluid (BALF) was collected for determination of the concentrations of CCSP by enzyme-linked immunosorbent assay, and the expression of CCSP in the bronchial epithelium in right lung tissues was determined by immunohistochemistry. Results:Compared with group C, the expression of CCSP in the bronchial epithelium was significantly down-regulated, and the concentrations of CCSP in BALF were decreased in the other three groups ( P<0.05 or 0.01). Compared with ALI group and ALI+ vehicle group, the histopathological injury was significantly reduced, the expression of CCSP in the bronchial epithelium was up-regulated, and the concentrations of CCSP in BALF were increased in ALI+ AhR antagonist group ( P<0.01). Conclusions:AhR partially mediates the down-regulation of CCSP expression during endotoxin-induced lung injury in rats.
ABSTRACT
Objective:To analyze the changes in plasma endothelin-1 (ET-1) concentrations in the patients with acute respiratory distress syndrome (ARDS).Methods:Fourteen patients with ARDS induced by trauma, 8 males and 6 females, aged 19-80 yr, were studied. The severity of ARDS was graded according to the Berlin definition of ARDS after admission to intensive care unit (ICU). Venous blood samples were obtained on 1st, 3rd and 5th days after admission to ICU, the plasma ET-1 concentrations were measured by radioimmunoassay, the pulmonary vascular permeability index (PVPI) was determined by PiCCO technique, and multiple organ dysfunction (MOD) score and lung injury score (LIS) were assessed. Spearman correlation of plasma ET-1 concentrations with MOD score, LIS and PVPI was analyzed.Results:MOD score, LIS, PVPI and plasma ET-1 concentrations were significantly decreased in mild ARDS patients ( n=5) as compared with moderate ARDS patients ( n=9, P<0.05). The plasma ET-1 concentration was positively correlated with MOD score, LIS and PVPI ( r=0.69, 0.76, 0.62, P<0.001). Conclusions:Plasma ET-1 concentrations can reflect the pulmonary vascular permeability and even the severity of the disease in the early stage of ARDS, so it is necessary to carry out dynamic monitoring in the patients.