Effect of α7nAChR agonists on acute lung injury caused by cardiopulmonary bypass in rats

Abstract

Objective To evaluate the effect of α7 nicotinic acetylcholine receptor(α7nAChR) agonists on lung injury caused by cardiopulmonary bypass (CPB) in rats. Methods Eighteen healthy clean-grade adult male Sprague-Dawley rats, weighing 350-400 g, were divided into 3 groups (n=6 each) using a random number table method: sham operation group (group S), CPB group and α7nAChR agonist PHA568487 group (group PHA). The rats underwent no CPB and were mechanically ventilated for 60 min in group S. PHA568487 0.8 mg/kg (diluted to 2 ml in normal saline) was intraperitoneally injected at 30 min before CPB, and then CPB was performed for 60 min in group PHA.Normal saline 2 ml was intraperitoneally injected at 30 min before CPB, and then CPB was performed for 60 min in group CPB.Blood samples were collected from the internal jugular vein for determination of serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) concentrations by enzyme-linked immunosorbent assay.Lung tissues were obtained for microscopic examination of the pathologic changes and for determination of wet/dry weight ratio (W/D ratio) and matrix metalloproteinase-9 (MMP-9) expression (by Western blot). Results Compared with group S, the W/D ratio and serum concentrations of TNF-α and IL-6 were significantly increased, and the expression of MMP-9 was up-regulated in CPB and PHA groups (P<0.05). Compared with group CPB, the W/D ratio and serum concentrations of TNF-α and IL-6 were significantly decreased, the expression of MMP-9 was down-regulated (P<0.05), and the pathological changes of lung tissues were significantly attenuated in group PHA (P<0.05). Conclusion α7nAChR agonists can reduce the acute lung injury caused by CPB in rats, and the mechanism may be related to down-regulating MMP-9 expression and inhibiting systemic inflammatory responses. Key words: Cholinergic agonists; Cardiopulmonary bypass; Respiratory distress syndrome, adult