Penehyclidine hydrochloride postconditioning on lipopolysaccharide-induced acute lung injury by inhibition of inflammatory factors in a rodent model.

BACKGROUND: Sepsis is associated with acute lung injury (ALI) and high mortality. The aim of this study was to investigate the effects of different doses of penehyclidine hydrochloride (PHC) postconditioning on ALI induced by sepsis in a rat model. METHODS: A rat model of ALI was induced by intravenous injection of lipopolysaccharide (LPS). The different doses of PHC were administrated intravenously at 30 min after LPS administration (low dose, 0.3 mg/kg; medium dose, 1.0 mg/kg, and high dose, 3.0 mg/kg). After 6 h, arterial blood samples were obtained for blood gas analyses. Meanwhile, lung tissue was harvested and lung injury was assessed by the histopathologic changes (hematoxylin and eosin staining) and wet-to-dry lung weight ratio. The tumor necrosis factor-α and interleukin-6 levels in bronchoalveolar lavage fluid, as well as the nuclear factor-kappa B protein expressions, and the myeloperoxidase activities in lung tissues were measured by immunohistochemistry or enzyme-linked immunosorbent assay, respectively. RESULTS: LPS-induced severe lung injury evidenced by increased pathologic scores and lung wet-to-dry weight ratio, which was accompanied by increases in the expression of pulmonary nuclear factor-kappa B protein and the activity of pulmonary myeloperoxidase and the levels of interleukin-6 and tumor necrosis factor-α in bronchoalveolar lavage fluid. The arterial oxygen tension (PaO2), pH, and the PaO2/fraction of inspired oxygen ratio (PaO2/FiO2) decreased significantly and the carbon dioxide tension (PaCO2) increased notedly after an LPS injection. All doses of PHC could significantly ameliorate lung injury and improve the previously mentioned variables (P < 0.05 or 0.01). Furthermore, the protection of medium dose (1.0 mg/kg) could be better than that of low or high dose. CONCLUSIONS: These findings indicated that different doses of PHC, especially to medium dose, could prevent LPS-induced ALI in rats, at least in part, by inhibiting inflammatory response. Moreover, the protection of pharmacologic postconditioning with PHC is limited by a "ceiling effect."