Salidroside Attenuates Ventilation Induced Lung Injury via SIRT1-Dependent Inhibition of NLRP3 Inflammasome

Cell Physiol Biochem. 2017;42(1):34-43. doi: 10.1159/000477112. Epub 2017 May 10.

Abstract

Background: Salidroside (SDS) is the main effective ingredient of Rhodiola rosea L with a variety of pharmacologic properties. We aim to investigate the effects of SDS on ventilation induced lung injury (VILI) and explore the possible underlying molecular mechanism.

Methods: Lung injury was induced in male ICR mice via mechanical ventilation (30 ml/kg) for 4h. The mice were divided in four groups:(1) Control group; (2) Ventilation group; (3) SDS group; (4) Ventilation with SDS group. SDS (50 mg/kg) was injected intraperitoneally 1h before operation. Mouse lung vascular endothelial cells (MLVECs) were subjected to cyclic stretch for 4h.

Results: It was found that SDS attenuated VILI as shown in HE staining, cell count and protein content levels in BAL fluid, W/D and Evans blue dye leakage into the lung tissue. SDS treatment inhibited the activation of NLRP3 inflammasome and subsequent caspase-1 cleavage as well as interleukin (IL)-1β secretion both in vivo and in vitro. Moreover, SDS administration up-regulated SIRT1 expression. Importantly, knockdown of SIRT1 reversed the inhibitory effect of SDS on NLRP3 inflammasome activation.

Conclusions: Taken together, these findings indicate that SDS may confer protection against ventilation induced lung injury via SIRT1-de-pendent inhibition of NLRP3 inflammasome activation.

Keywords: Cyclic stretch; NLRP3 inflammasome; SIRT1; Salidroside; Ventilation-induced lung injury.

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Caspase 1 / metabolism
  • Cells, Cultured
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Glucosides / pharmacology*
  • Glucosides / therapeutic use
  • Inflammasomes / metabolism
  • Interleukin-1beta / analysis
  • Interleukin-1beta / metabolism
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Mice
  • Mice, Inbred ICR
  • NLR Family, Pyrin Domain-Containing 3 Protein / antagonists & inhibitors
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Phenols / pharmacology*
  • Phenols / therapeutic use
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Sirtuin 1 / antagonists & inhibitors
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism*
  • Stress, Mechanical
  • Up-Regulation / drug effects*
  • Ventilator-Induced Lung Injury / metabolism
  • Ventilator-Induced Lung Injury / pathology
  • Ventilator-Induced Lung Injury / prevention & control

Substances

  • Glucosides
  • Inflammasomes
  • Interleukin-1beta
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Phenols
  • RNA, Small Interfering
  • Caspase 1
  • Sirt1 protein, mouse
  • Sirtuin 1
  • rhodioloside