Effects of penehychdine hydrochloride on TLR4 mRNA expression during endotoxin-induced acute lung injury in neonatal rats

Abstract

Objective To evaluate the effects of penehychdine hydrochloride on Toll-like receptor 4 (TLR4) mRNA expression during endotoxin-induced acute lung injury (ALI) in neonatal rats. Methods Thirty pathogen-free male Wistar rats, aged 7 days, weighing 12-18 g, were randomly divided into 3 groups (n=10 each) using a random number table: normal saline group (group NS), ALI group, and penehychdine hydrochloride group (group PH). ALI was induced with intraperitoneal endotoxin 5 mg/kg. In group PH, penehychdine hydrochloride 0.5 mg/kg was injected intraperitoneally at 30 min before ALI, while the equal volume of normal saline was given instead in group NS.At 4 h after endotoxin injection, the rats were sacrificed, and lungs were removed for determination of TLR4 mRNA expression (using real-time reverse transcriptase polymerase chain reaction), and contents of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-10 in the lung tissues (by enzyme-linked immunosorbent assay), and for examination of the pathologic changes of lung (with electron microscope). Results Compared with group NS, TLR4 mRNA expression was significantly up-regulated, and contents of TNF-α, IL-1β, and IL-10 were increased in ALI and PH groups.Compared with group ALI, TLR4 mRNA expression was significantly down-regulated, and contents of TNF-α, IL-1β, and IL-10 were decreased in group PH.The pathologic changes of lung were significantly mitigated in group PH compared with group ALI. Conclusion Penehychdine hydrochloride inhibits inflammatory responses through down-regulating TRL4 mRNA, thus reducing endotoxin-induced ALI in neonatal rats. Key words: Cholinergic antagonists; Infant, newborn; Endotoxemia; Respiratory distress syndrome, adult; Toll-like receptor 4