Effect of penehyclidine hydrochloride on cell apoptosis during acute lung injury induced by "two-hit" in rats

Objective To evaluate the effect of penehyclidine hydrochloride on cell apoptosis during acute lung injury (ALI) induced by two-hit in rats. Methods Thirty male SPF Sprague-Dawley rats, aged 8 weeks, weighing 240-270 g, were randomly assigned into 3 groups (n=10 each) using a random number table: sham operation group (group Sham), ALI induced by blunt chest trauma and hemorrhagic shock group (group ALI), and penehyclidine hydrochloric group (group PHC). In ALI and PHC groups, the rats were subjected to the combination of chest trauma and hemorrhage (mean arterial pressure 35-40 mmHg mm Hg, lasting for 60 min) to establish a model of ALI.In group PHC, penehyclidine hydrochloric 2 mg/kg was injected intraperitoneally at 1 h before blunt chest trauma.At 8 h after successful establishment of the model, the rats were sacrificed, and lungs were removed for examination of the pathologic changes and for determination of Bax, Bcl-2 and caspase-3 expression (using Western blot), tumor necrosis factor-alpha (TNF-α) content (by enzyme-linked immunosorbent assay), and cell apoptosis (by TUNEL). Apoptotic index was calculated. Results Compared with group Sham, the levels of Bax, caspase-3 and TNF-α and apoptotic index were significantly increased, and Bcl-2 expression was down-regulated in ALI and PHC groups.Compared with group ALI, the levels of Bax, caspase-3 and TNF-α and apoptotic index were significantly decreased, and Bcl-2 expression was up-regulated in group PHC.The pathologic changes of lungs were significantly reduced in group PHC than in group ALI. Conclusion Penehyclidine hydrochloride mitigates ALI induced by two-hit through inhibiting cell apoptosis in rats. Key words: Cholinergic antagonists; Thoracic injury; Shock, hemorrhagic; Respiratory distress syndrome, adult; Apoptosis