Simvastatin Ameliorates PAK4 Inhibitor-Induced Gut and Lung Injury.

P21 activated kinase 4 (PAK4), a key regulator of cytoskeletal rearrangement and endothelial microparticles (EMPs), is released after lipopolysaccharide (LPS) stimulation. In addition, it participates in LPS-induced lung injury. In this study, forty-eight Sprague Dawley (SD) rats were divided into t...

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Publicado en:BioMed Research International Vol. 2017; pp. 1 - 10
Autores principales: Pan, Shuming, Wu, Zengbin, Liu, Xuan, Chen, Jiameng, Wang, Huiqi, Liu, Dan, Fei, Aihua, Chen, Liang, Gao, Chengjin
Formato: diagnostic images research tables/charts Journal Article
Publicado: Wiley-Blackwell 12/28/2017
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 12/28/2017
      vid: 2017
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        127006688
        127006688
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        10.1155/2017/8314276
        127006688
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      tig:
        atl: Simvastatin Ameliorates PAK4 Inhibitor-Induced Gut and Lung Injury.
      aug:
        au:
          Pan, Shuming
          Wu, Zengbin
          Liu, Xuan
          Chen, Jiameng
          Wang, Huiqi
          Liu, Dan
          Fei, Aihua
          Chen, Liang
          Gao, Chengjin
        affil: Emergency Department, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
      sug:
        subj:
          Acute Lung Injury Physiopathology
          Simvastatin Therapeutic Use
          Intestinal Mucosa Physiology
          Animal Studies
          Rats
          Protein Kinases
          Lipopolysaccharides
          Inflammation Mediators
      ab: P21 activated kinase 4 (PAK4), a key regulator of cytoskeletal rearrangement and endothelial microparticles (EMPs), is released after lipopolysaccharide (LPS) stimulation. In addition, it participates in LPS-induced lung injury. In this study, forty-eight Sprague Dawley (SD) rats were divided into two groups, including PAK4 inhibitor (P) and PAK4 inhibitor + simvastatin (P + S) treatment groups. All rats were given PAK4 inhibitor (15 mg/kg/d) orally. Immediately after PAK4 inhibitor administration, simvastatin was injected intraperitoneally to P + S group animals at 20 mg/kg/day. Then, treatment effects on the intestinal mucosal barrier and lung injury caused by PAK4 inhibitor and simvastatin were assessed. The results showed that gut Zonula Occludens- (ZO-) 1, PAK4, mitogen-activated protein kinase 4 (MPAK4), and CD11c protein levels were reduced, while plasma endotoxin levels were increased after administration of PAK4 inhibitor. Furthermore, compared with normal rats, wet-to-dry (W/D) values of lung tissues and circulating EMP levels were increased in the treatment group, while PAK4 and CD11c protein amounts were reduced. Therefore, in this lung injury process induced by PAK4 inhibitor, the protective effects of simvastatin were reflected by intestinal mucosal barrier protection, inflammatory response regulation via CD11c+ cells, and cytoskeleton stabilization. In summary, PAK4 is a key regulator in the pathophysiological process of acute lung injury (ALI) and can be a useful target for ALI treatment.
      pubtype: Academic Journal
      doctype:
        diagnostic images
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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