Effect of penehyclidine hydrochloride pretreatment on hypoxia-inducible factor-1alpha expression in lung tissues in rats with acute lung injury induced by lipopolysaccharide / 中华麻醉学杂志

ABSTRACT

Objective To investigate the effects of penehyclidine hydrochloride (PHCD) pretreatment on hypoxia-inducible factor-1alpha (HIF-1α) expression in lung tissues in rats with acute lung injury (ALI) induced by lipopolysaccharide (LPS).Methods One hundred and twenty female Sprague-Dawley rats,weighing 180-220g,were randomly divided into 3 groups (n =40 each)control group (group C),ALI group and PHCD pretreatment group (group P).ALI was induced by intraperitoneal LPS 5 mg/kg in ALI and P groups.The equal volume of normal saline was given intraperitoneally in group C.Group P received intraperitoneal PHCD 2 mg/kg at 30 min before LPS administration.Eight rats in each group were chosen at 2,4,8 and 24 h after LPS administration,and the lung was removed for determination of HIF-1α mRNA expression in lung tissues by RT-PCR.Eight rats in each group were chosen at 6 h after LPS administration,and the lung was removed for determination of W/D lung weight ratio and IL-6 content (by ELISA) and for microscopic examination.Results The W/D lung weight ratio and IL-6 content at 6 h after LPS administration and HIF-1α mRNA expression at each time point after LPS administration were significantly higher in groups P and ALI than in group C (P ＜ 0.05),and lower in group P than in group ALI(P ＜ 0.05).The pathological damage was significantly ameliorated in group P as compared with group ALI.Conclusion PHCD can reduce LPS-induced ALI through down-regulation of HIF-1α expression in lung tissues and inhibition of the inflammatory response in rats.