Effect of penehyclidine hydrochloride on endotoxemia-induced intestinal injury in neonatal rats

Abstract

Objective To investigate the effect of penehyclidine hydrochloride on endotoxemia-induced intestinal injury in neonatal rats. Methods Ninety healthy neonatal Sprague-Dawley rats, aged 7 days, weighing 16-20 g, were randomly divided into 3 groups (n=30 each) using a random number table: control group (group C), lipopolysaccharide (LPS) group, and penehyclidine hydrochloride group (group P). Endotoxemia was induced by intraperitoneal LPS 5 mg/kg in LPS and P groups. In group P, penehyclidine 2 mg/kg was injected intraperitoneally at 30 min before and after LPS injection. The equal volume of normal saline was given in group C. At 2, 6 and 12 h after LPS or normal saline administration, 10 rats in each group were randomly chosen and sacrificed. The ileum was removed to detect wet/dry lung weight ratio (W/D ratio) and contents of tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), hypoxia-inducible factor 1 alpha (HIF-1α) and glutamine (Gln), and for examination of the pathologic changes of the ileum with light microscope. Results Compared with group C, the W/D ratio and contents of TNF-α, IL-6 and HIF-1α were significantly increased, and the content of Gln was decreased at each time point in LPS and P groups. Compared with group LPS, the W/D ratio and contents of TNF-α, IL-6 and HIF-1α were significantly decreased, the content of Gln was increased at each time point, and the pathologic changes of the ileum were mitigated in group P. Conclusion Penehyclidine hydrochloride can reduce endotoxemia-induced intestinal injury in the neonatal rats, and down-regulated expression of HIF-1α, up-regulated expression of Gln and attenuated inflammatory responses may be involved in the mechanism. Key words: Cholinergic antagonists; Endotoxemia; Intestine; Infant, newborn