Effects of penehyclidine preconditioning on MAPK pathway in lung injury induced by sepsis in mice

Abstract

Objective To investigate the effects of penehyclidine preconditioning on mitogen-activated protein kinase (MAPK) pathway in the lung injury induced by sepsis in mice. Methods Methods One hundred and five healthy female mice weighing 20-25 g were randomly divided into 3 groups (n=35 each):group Ⅰ sham operation (S);group Ⅱ sepsis and group Ⅲ PHP + sepsis. Sepsis was produced by cecal ligation and puncture (CLP). In group Ⅲ penehyclidine 0.45 mg/kg was administered intraperitoneally 1 h before CLP. Pulmonary microvascalar permeability was determined with intravenous Evans blue given instantly after surgery in 10 animals in each group. Arterial blood gas analysis was performed at 12 h after CLP, and the animals were killed. The lungs were immediately removed for histological examination with light microscope and determination of SOD activity, MDA content, and expression of phosphorylated p38 MAPK, ERK1/ERK2 and JNK in the lung tissue. Results Compared with control group (S), CLP significantly decreased PaO2, PaO2,/FiO2 and pH;increased pulmonary micrevascalar permeability, MDA content and expression of p38 MAPK, ERK1/ERK2 and JNK in the lung tissue. PHP significantly attenuated CLP-induced changes in blood gas, pulmonary microvascular permeability, MDA content and expression of p38 MARK, ERK1/ERK2, and JNK in the lung tissue. Conclusion Penehyclidine preconditioning can ameliorate lung injury induced by sepsis through inhibition of MAPK (p38 MAPK and ERK1/ERK2) activation. Key words: Cholinergic antagonists; p38 mitogen-activated protein kinases; Extracellular signal-regulated MAP kinases; JNK mitogen-activated protein kinases; Ischemic preconditioning; Respiratory distress syndrome, adult; Sepsis