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

  • J Inflamm Res. 2021 Apr 16:14:1537-1549. doi: 10.2147/JIR.S299267.
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 Wang  1
Affiliations
  • 1. Department 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.
  • 2. Wenzhou Medical University, Wenzhou, People's Republic of China.
  • 3. Institute of Inflammation and Aging, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
PMID: 33889010 DOI: 10.2147/JIR.S299267
Abstract

Background: 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
Na,K-ATPases; acute respiratory distress syndrome; alveolar fluid clearance; rosuvastatin; sodium channel.
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