Penehyclidine hydrochloride decreases pulmonary microvascular permeability by upregulating beta arrestins in a murine cecal ligation and puncture model

• Published in: The Journal of surgical research 2015-01, Vol.193 (1), p.391-398
• Main Authors: Zhan, Jia, MD, PhD, Xiao, Fei, MD, Li, Jin-Jie, MD, Zhang, Zong-Ze, MD, PhD, Chen, Kai, MD, PhD, Wang, Yi-Peng, MD, Wang, Yan-Lin, MD, PhD
• Format: Article
• Language: English
• Subjects: Acute Lung Injury - drug therapy; Acute Lung Injury - metabolism; Animals; Arrestins - metabolism; Beta arrestins; Capillary Permeability - drug effects; Cecal ligation and puncture; Cecum - injuries; Cholinergic Antagonists - chemistry; Cholinergic Antagonists - pharmacology; Disease Models, Animal; Female; Ligation; Lung - blood supply; Lung - metabolism; Mice, Inbred Strains; Microcirculation - drug effects; NF-kappa B - metabolism; Penehyclidine hydrochloride; Pulmonary Circulation - drug effects; Pulmonary microvascular permeability; Quinuclidines - chemistry; Quinuclidines - pharmacology; Random Allocation; Surgery; Up-Regulation - drug effects; Wounds, Stab
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2014.07.002

Abstract Background Penehyclidine hydrochloride (PHC) is a new anticholinergic drug, which has been shown to have a good curative effect for sepsis. Beta arrestins have been demonstrated to play important roles in sepsis. This study is to investigate the effects of PHC on pulmonary microvascular permeability and on expressions of beta arrestins in lung injury induced by the cecal ligation and puncture (CLP) procedure. Materials and methods Thirty healthy female mice were randomly divided into three groups ( n = 10 each): sham operation group (control group), CLP group (CLP group), and PHC 0.45 mg/kg group (PHC group). In the PHC group, mice were given an intraperitoneal injection of PHC 0.45 mg/kg 1 h before surgery. Mice in the other two groups received an intraperitoneal injection of the same volume of normal saline. At 12 h after surgery, serum and bronchoalveolar lavage fluid were collected to examine lung permeability index. The lung tissue samples were collected to examine expressions of myosin light chain kinase (MLCK), vascular endothelial-cadherin (VE-cadherin), vascular cell adhesion molecule 1 (VCAM-1), myeloperoxidase (MPO), NF-κB, and beta arrestins. Results Compared with the control group, pulmonary microvascular permeability, MPO activity, NF-κB, VCAM-1, and MLCK expressions were significantly increased, whereas VE-cadherin and beta-arrestin protein expressions were obviously decreased in CLP group. Furthermore, compared with the CLP group, PHC group markedly decreased pulmonary microvascular permeability, MPO activity, NF-κB, VCAM-1, and MLCK expressions, and increased expressions of VE-cadherin and beta arrestins. Conclusions This study suggests that in the CLP-induced lung injury model, PHC could reduce pulmonary microvascular permeability by upregulating expressions of beta arrestins.