title: Penehyclidine hydrochloride decreases pulmonary microvascular permeability by upregulating beta arrestins in a murine cecal ligation and puncture model.
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.
  
  
  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.
authors.affiliation: Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Zhan
authors.affiliation: Department of Osteology, Pu Ai Hospital, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Department of Anesthesiology, Hospital of Stomatology, Wuhan University, Wuhan, Hubei, People's Republic of China.
authors.forename: Jin-Jie
authors.initials: JJ
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
authors.forename: Zong-Ze
authors.initials: ZZ
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
authors.forename: Yi-Peng
authors.initials: YP
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China. Electronic address: jia19811001@163.com.
authors.forename: Yan-Lin
authors.initials: YL
authors.lastname: Wang
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D019390:Arrestins / Q000378:metabolism*; D002199:Capillary Permeability / Q000187:drug effects; D002432:Cecum / Q000293:injuries; D018680:Cholinergic Antagonists / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D008026:Ligation; D008168:Lung / Q000098:blood supply* / Q000378:metabolism; D008815:Mice, Inbred Strains; D008833:Microcirculation / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects; D011812:Quinuclidines / Q000737:chemistry / Q000494:pharmacology*; D011897:Random Allocation; D015854:Up-Regulation / Q000187:drug effects; D014951:Wounds, Stab; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D018680:Cholinergic Antagonists; D016328:NF-kappa B; D011812:Quinuclidines; D000071557:beta-Arrestins; C486140:penehyclidine
keywords: Beta arrestins; Cecal ligation and puncture; Penehyclidine hydrochloride; Pulmonary microvascular permeability