Effect of penehyclidine hydrochloride on expression of caveolin-1 during LPS-induced lung injury in rats

Abstract

Objective To evaluate the effect of penehyclidine hydrochloride (PHC) on the expression of caveolin-1 (Cav-1) with lipopolysaccharide (LPS)-induced lung injury (LI)in rats. Methods Thirty SPF healthy male Sprague-Dawley rats, weighing 170-190 g, were divided into 3 groups (n=10 each) using a random number table method: control group (group C), LPS-induced LI group (group LI) and PHCD group.LI was produced by injecting LPS 0.2 ml (5 mg/kg) via the trachea in anesthetized rats. PHCD 0.5 ml (2 mg/kg) was intraperitoneally injected at 1 h before establishing the model in group PHCD. Arterial blood samples were collected at 24 h after establishing the model for blood gas analysis and for determination of serum tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) concentrations by enzyme-linked immunosorbent assay. Rats were then sacrificed, and the lungs were removed. The main bronchus was lavaged, and the broncho-alveolar lavage fluid (BALF) was collected for calculation of the percentage of polymorphonuclear neutrophils (PMNs). Lung tissues were obtained for examination of pathological changes and for determination of myeloperoxidase(MPO)activity (by colorimetric assay), wet/dry weight ratio (W/D ratio), and expression of Cav-1 and nuclear factor kappa B (NF-κB) in nucleoprotein (by Western blot). Results Compared with group C, pH value and PaO2 were significantly decreased, the PaCO2, percentage of PMNs in BALF, W/D ratio and MPO activity were increased, the Cav-1 expression was down-regulated, the expression of NF-κB in nucleoprotein was up-regulated, and the serum TNF-α and IL-1β concentrations were increased in group LI (P 0.05). Conclusion The mechanism by which PHC reduces LPS-induced LI may be related to up-regulating the expression of Cav-1 and mitigating inflammatory responses in lung tissues of rats. Key words: Cholinergic antagonists; Caveolin-1; Endotoxemia; Respiratory distress syndrome, adult