Effects of penehyclidine hydrochloride pretreatment on expression of β-arrestin-1 during sepsis-induced acute lung injury in mice

Abstract

Objective To investigate the effects of penehyclidine hydrochloride (PHCD) pretreatment on β-arrestin-1 expression during sepsis-induced acute lung injury in mice.Methods Thirty female Kunming mice,weighing 18-20 g,were randomly divided into 3 groups (n =10 each):sham operation group (S group),sepsis group (CLP group) and PHCD group.Sepsis was induced by cecal ligation and puncture (CLP).In PHCD group,PHCD 0.45 mg/kg was injected intraperitoneally 1 h before CLP.The equal volume of normal saline was given instead in groups S and CLP.The mice were sacrificed at 12 h after CLP,bronchoalveolar lavage fluid (BALF) was collected for measurement of the total protein concentration,and the lungs were removed for determination of wet/dry lung weight ratio and expression of myosin light chain kinase (MLCK),vascular endothelial cadherin (VE-cad-herin) and β-arrestin-1 in lung tissues.The pathological changes of the lung were scored.Results Compared with group S,the lung injury score,wet/dry lung weight ratio and total protein concentration in BALF were significantly increased,MLCK expression was up-regulated and VE-cadherin expression was down-regulated in groups CLP and PHCD,β-arrestin-1 expression was down-regulated in group CLP and β-arrestin-1 expression was up-regulated in group PHCD (P ＜ 0.05 or 0.01).The lung injury score,wet/dry lung weight ratio,total protein concentration in BALF,and MLCK expression were significantly lower,while the expression of VE-cadherin and β-arrestin-1 was higher in PHCD group than in CLP group (P ＜ 0.05 or 0.01).Conclusion PHCD pretreatment can ameliorate acute lung injury through up-regulating β-arrestin-1 expression and reducing microvascular permeability in septic mice. Key words: Cholinergic antagonists ; Arrestins ; ; Respiratory distress syndrome, adult ; Sepsis