Penehyclidine Hydrochloride Alleviates Lipopolysaccharide-Induced Acute Lung Injury by Ameliorating Apoptosis and Endoplasmic Reticulum Stress

Abstract

BackgroundPenehyclidine hydrochloride (PHC), a novel anticholinergic reagent, has been shown to exert anti–endoplasmic reticulum stress (ERS), antioxidant, and antiinflammation functions in various rat models. However, the definite pathogenesis of lung defensive roles of PHC remains unclear. This study measured the functions of PHC on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats. MethodsIn this research, the LPS-induced ALI model was assessed through the branchial injection of LPS for 24 h. Male Sprague-Dawley rats were randomly allocated into 5 groups: sham, LPS, LPS + PHC (0.5 mg/kg), LPS + PHC (1 mg/kg), and LPS + PHC (2.5 mg/kg). The concentrations of superoxide dismutase, malondialdehyde, myeloperoxidase, and glutathione peroxidase were measured by enzyme-linked immunosorbent assay and immunohistochemistry analysis. Western blotting, real-time PCR, and immunofluorescence analysis were used to determine the ERS-associated protein levels and mRNA expression. The protein levels of Bax, Bcl-2, caspase-3, and caspase-9 were used to measure lung tissue apoptosis. ResultsThe results revealed that PHC administration inhibited LPS-induced ALI as indicated by the loss in the ratio of injury production evaluated through hematoxylin-eosin staining, in particular the lung sample sections, compared with the LPS group. PHC administration inhibited LPS-induced lung myeloperoxidase and serum concentrations of malondialdehyde, superoxide dismutase, and glutathione peroxidase in rats. PHC administration repressed the LPS-activated ERS-correlated pathway and apoptosis-associated protein levels in rats. ConclusionsIn summary, our findings indicated that PHC has a defensive effect on LPS-induced ALI by inhibiting oxidative stress, attenuating PERK and ATF6 signals, and suppressing ERS-mediated apoptosis.