Journal of Inflammation Research (Apr 2021)

Rosuvastatin Enhances Alveolar Fluid Clearance in Lipopolysaccharide-Induced Acute Lung Injury by Activating the Expression of Sodium Channel and Na,K-ATPase via the PI3K/AKT/Nedd4-2 Pathway

  • Xu HR,
  • Yang Q,
  • Xiang SY,
  • Zhang PH,
  • Ye Y,
  • Chen Y,
  • Xu KW,
  • Ren XY,
  • Mei HX,
  • Shen CX,
  • Ma HY,
  • Smith FG,
  • Jin SW,
  • Wang Q

Journal volume & issue
Vol. Volume 14
pp. 1537 – 1549

Abstract

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Hao-Ran Xu,1 Qian Yang,1 Shu-Yang Xiang,1 Pu-Hong Zhang,1 Yang Ye,1 Yan Chen,1 Ke-Wen Xu,2 Xi-Ya Ren,2 Hong-Xia Mei,1 Chen-Xi Shen,1 Hong-Yu Ma,1 Fang-Gao Smith,1,3 Sheng-Wei Jin,1 Qian Wang1 1Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China; 2Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Institute of Inflammation and Aging, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UKCorrespondence: Sheng-Wei Jin; Qian WangDepartment of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou, Zhejiang Province, 325027, People’s Republic of ChinaTel +86 577-88002806Fax +86 577-88832693Email [email protected]; [email protected]: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are devastating clinical conditions characterized by pulmonary epithelial damage and protein-rich fluid accumulation in the alveolar spaces. Statins are a class of HMG-CoA reductase inhibitors, which exert cholesterol-lowering and anti-inflammatory effects.Methods: Rosuvastatin (1 mg/kg) was injected intravenously in rats 12 h before lipopolysaccharide (LPS, 10 mg/kg) administration. Eight hours later after LPS challenge, alveolar fluid clearance (AFC) was detected in rats (n = 6– 8). Rosuvastatin (0.3 μmol/mL) and LPS were cultured with primary rat alveolar type II epithelial cells for 8 h.Results: Rosuvastatin obviously improved AFC and attenuated lung-tissue damage in ALI model. Moreover, it enhanced AFC by increasing sodium channel and Na,K-ATPase protein expression. It also up-regulated P-Akt via reducing Nedd4-2 in vivo and in vitro. Furthermore, LY294002 blocked the increase in AFC in response to rosuvastatin. Rosuvastatin-induced AFC was found to be partly rely on sodium channel and Na,K-ATPase expression via the PI3K/AKT/Nedd4-2 pathway.Conclusion: In summary, the findings of our study revealed the potential role of rosuvastatin in the management of ALI/ARDS.Keywords: acute respiratory distress syndrome, rosuvastatin, alveolar fluid clearance, sodium channel, Na,K-ATPases

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