Effects of penehyclidine hydrochloride on activities of NF-κB and AP-1 during actue lung injury induced by blunt chest trauma-hemorrhagic shock and resuscitation in rats

Abstract

Objective To investigate the effects of penehyclidine hydrochloride on activities of nuclear factor kappa B(NF-κB) and activator protein-1 (AP-1) during actue lung injury induced by blunt chest trauma-hemorrhagic shock and resuscitation (HSR) in rats. Methods Thirty male Sprague-Dawley rats, aged 8 weeks, weighing 250-300 g, were randomly assigned into 3 equal groups (n = 10 each) using a random number table: sham operation group (group S), blunt chest trauma-HSR group (group THSR) and penehyclidine hydrochloride group (group PHCD). The model of actue lung injury induced by blunt chest trauma-HSR was induced by dropping a 300 g weight onto a precordium in anesthetized rats.Blood was withdrawn via the femoral artery 5 min later until MAP was decreased to 35-45 mmHg within 15 min and maintained at this level for 60 min, followed by resuscitation.In PHCD group, PHCD 2 mg/kg was injected intravenously at 60 min after hemorrhagic shock.At 6 h after the model was established, blood samples were obtained for measurement of concentrations of tumor necrosis factor-alpha (TNF-α) in serum.The lungs were then removed for determination of lung water content, myeloperoxidase (MPO) activaty (by colorimetric assay), NF-κB and AP-1 activaties (using electrophoretic mobility shift assay) in lung tissues, and for microscopic examination of pathologic changes (under light microscope). The left lung was lavaged, and lung permeability index (LPI) was calculated. Results Compared with S group, lung water content, LPI, serum TNF-α level and activites of MPO, NF-κB and AP-1 were significantly increased in THSR and PHCD groups.Compared with THSR group, lung water content, LPI, serum TNF-α concentrations and activites of MPO, NF-κB and AP-1 were significantly decreased in PHCD group.The pathological damage to lung tissues was significantly reduced in PHCD group as compared with THSR group. Conclusion PHCD can inhibit activities of NF-κB and AP-1 in lung tissues, thus mitigating acute lung injury induced by blunt chest trauma-HSR in rats. Key words: NF-κappa B; Transcription factor AP-1; Cholinergic antagonists; Thoracic injury; Shock, hemorrhagic; Respiratory distress syndrome, adult