title: Pretreatment with andrographolide pills(®) attenuates lipopolysaccharide-induced pulmonary microcirculatory disturbance and acute lung injury in rats.
abstract: OBJECTIVE
  The purpose of this study was to explore the protective effect of AP on LPS-induced PMD and ALI.
  
  
  METHODS
  Male SD rats were continuously infused with LPS (5 mg/kg/h) for one hour to induce PMD and ALI. AP was administrated orally one hour before LPS exposure. Arterial blood pressure and HR were monitored. Blood gas analysis, histological observation, cytokines in plasma, leukocyte recruitment, pulmonary oxidative stress, microvessel permeability, edema, and related proteins were evaluated six hours after LPS challenge.
  
  
  RESULTS
  Rats receiving LPS exhibited significant alterations, including hypotension, tachycardia, increase in cytokines, neutrophil adhesion and infiltration, oxidative stress, and microvessel hyperpermeability, resulting in pulmonary injury and dysfunction. AP (0.18 g/kg or 1.8 g/kg) improved rat survival rate, and significantly attenuated all aforementioned insults, and inhibited LPS-induced increase in adhesion molecules, up-regulation of Cav-1 and Src kinase and NADPH oxidase subunits (p47(phox) and p67(phox) ) membrane translocation in lung tissue, and preserved JAM-1 and claudin-5.
  
  
  CONCLUSIONS
  The results demonstrated the protective effect of AP on LPS-induced PMD and ALI, suggesting the potential of AP as a prophylactic strategy for LPS-induced ALI.
authors.affiliation: Tasly Microcirculation Research Center, Peking University Health Science Center, Beijing, China; Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, China; Department of Pharmacology, School of Basic Medical Sciences, Peking University, Beijing, China; Key Laboratory of Microcirculation, State Administration of Traditional Chinese Medicine of China, Beijing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Yang
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Liu
authors.forename: Chun-Shui
authors.initials: CS
authors.lastname: Pan
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Wei
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Mao
authors.forename: Fang
authors.initials: F
authors.lastname: Lin
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Li
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Fan
authors.forename: Jing-Yan
authors.initials: JY
authors.lastname: Han
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D062507:Claudin-5 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D051381:Rats
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015815:Cell Adhesion Molecules; D062507:Claudin-5; C491510:Cldn5 protein, rat; D016207:Cytokines; D004224:Diterpenes; C520495:F11r protein, rat; D008070:Lipopolysaccharides; C030419:andrographolide; D009247:NADH, NADPH Oxidoreductases; C583073:NCF2 protein, rat; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1
keywords: Src kinase; caveolin-1; hyperpermeability; leukocytes adhesion