Effect of penehyclidine hydrochloride on level of angiopoietin-1 and tyrosine kinase receptor-2 during endotoxin-induced acute lung injury in rats

Abstract

Objective To evaluate the effect of penehyclidine hydrochloride (PHC) on the level of angiopoietin-1 (Ang-1) and tyrosine kinase receptor-2 (Tie-2) during endotoxin-induced acute lung injury (ALI) in rats.Methods Forty adult male Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 4 groups using a random number table (n =10 each):control group (group C),ALI group,low-dose PHC group (group L-PHC) and high-dose PHC group (group H-PHC).ALI was induced with iv injection of lipopolysaccharide 5.0 mg/kg via the tail vein.In L-PHC and H-PHC groups,PHC 0.6 and 2 mg/kg were injected,respectively,via the tail vein at 1 and 24 h after lipopolysaccharide injection.The rats were sacrificed at 48 h after the initial injection of PHC to measure the lung water content,protein concentration in bronchoalveolar lavage fluid (BALF),and the expression of Ang-1,Tie-2 and phosphorylated Tie-2 in lung tissues.The morphological changes of lung tissues were observed under light microscope and the ultrastructural changes of alveolar epithelial barrier under transmission electron microscope.Results Compared with group C,the lung water content and protein concentrations in BALF were significantly increased,and the expression of Ang-1 and phosphorylated Tie-2 was down-regulated in the other three groups (P ＜ 0.05).Compared with group ALI,the lung water content and protein concentrations in BALF were significantly decreased,and the expression of Ang-1 and phosphorylated Tie-2 was up-regulated in H-PHC group (P ＜ 0.05),and no significant changes were found in the parameters mentioned above in group L-PHC (P ＞0.05).The damage to lung tissues was significantly reduced in group H-PHC as compared with group ALI.Conclusion PHC can improve the permeability of pulmonary microvascular and reduce injury to alveolar epithelial barrier,thus ameliorating endotoxin-induced ALI in rats,and the effect is dose-related and up-regulation of Ang-1 expression and inhancement of Tie-2 activity are involved in the mechanism. Key words: Cholinergic antagonist ; Respiratory distress syndrome, adult ; Endotoxemia; Angiopoietin-1 ; Receptor, protein-tyrosine kinases