Effect of Mechanical Ventilation on Plasma Concentration Level of R-spondin Proteins
Condition: Acute Lung Injury
MeSH terms: Lung Injury; Acute Lung Injury
Study type: Observational

Summary: 
      As novel agonists of Wnt/β-catenin signaling pathway, R-spondin proteins constitute a class
      of ligands, including R-spondin 1/2/3/4, functioning through their receptors leucine-rich
      repeat-containing G-protein coupled receptor (LGR)4/5/6 to enhance Wnt/β-catenin activity.
      Since Wnt signaling plays pivotal roles in the regulation of many life processes involved in
      embryogenesis and adulthood, R-spondin proteins also take part in cell proliferation,
      differentiation and morphogenesis.For example, in the formation of respiratory
      system，R-spondin 2 is required for normal laryngeal-tracheal and lung morphogenesis，and the
      lack of R-spondin 1 expression results in the absence of duct side-branching development and
      subsequent alveolar formation. In addition, R-spondins show protective effect in tissue
      injury and diseases. R-spondin 1 and R-spondin 3 have been reported to prevent chemotherapy-
      or radiotherapy-induced mucous membrane lesion. R-spondin 1 attenuates oral mucositis
      contributed by radiotherapy in mouse models and R-spondin 3 potentiates intestinal
      regeneration elicited via gastrointestinal toxic effect of chemoradiotherapy treatment.
      However, whether R-spondin proteins exert salient influence on acute lung injury especially
      induced by mechanical ventilation is deficient. Therefore, this study aims to ascertain the
      implication of R-spondin proteins in the pathology of mechanical ventilation induced lung
      injury through detecting human plasma concentration change of R-spondin 1/2/3/4 after
      mechanical ventilation and interference effects in mouse model, which is helpful for
      prevention and treatment of ventilation induced lung injury.
    

Detailed description: 
      Mechanical ventilation is a critical intervention for patients with acute respiratory
      failure. However, lung overdistension induced by mechanical ventilation also causes pulmonary
      endothelial dysfunction. The injurious effect of mechanical stretch on pulmonary endothelium
      has been implicated in the development of ventilator-induced lung injury, which is
      characterized by pulmonary inflammation and particularly increased vascular permeability. In
      addition, the investigators and others have previously shown that mechanical stretch
      increases cultured lung endothelial monolayer permeability in vitro and promotes lung
      vascular permeability in mice Thus, elucidating the mechanisms underlying the mechanical
      stretch-induced lung endothelial barrier dysfunction may provide a novel clinical therapeutic
      target against ventilator-induced lung injury.

      As novel agonists of Wnt/β-catenin signaling pathway, R-spondin proteins constitute a class
      of ligands, including R-spondin 1/2/3/4, functioning through their receptors leucine-rich
      repeat-containing G-protein coupled receptor (LGR)4/5/6 to enhance Wnt/β-catenin activity.
      Since Wnt signaling plays pivotal roles in the regulation of many life processes involved in
      embryogenesis and adulthood, R-spondin proteins also take part in cell proliferation,
      differentiation and morphogenesis. For example, in the formation of respiratory
      system，R-spondin 2 is required for normal laryngeal-tracheal and lung morphogenesis，and the
      lack of R-spondin 1 expression results in the absence of duct side-branching development and
      subsequent alveolar formation. In addition, R-spondins show protective effect in tissue
      injury and diseases. R-spondin 1 and R-spondin 3 have been reported to prevent chemotherapy-
      or radiotherapy-induced mucous membrane lesion. R-spondin 1 attenuates oral mucositis
      contributed by radiotherapy in mouse models and R-spondin 3 potentiates intestinal
      regeneration elicited via gastrointestinal toxic effect of chemoradiotherapy treatment.
      However, whether R-spondin proteins exert salient influence on acute lung injury especially
      induced by mechanical ventilation is deficient. Therefore, this study aims to ascertain the
      implication of R-spondin proteins in the pathology of mechanical ventilation induced lung
      injury through detecting human plasma concentration change of R-spondin 1/2/3/4 after
      mechanical ventilation and interference effects in mouse model, which is helpful for
      prevention and treatment of ventilation induced lung injury.
    

Intervention name(s): mechanical ventilation
Intervention type(s): Other
Intervention description(s): mechanical ventilation protocol: tidal volume 6-8 ml/kg, positive end-expiratory pressure 5 cm H2O, oxygen concentration 40%; respiratory rate 10-15/min, inspiratory/expiratory ratio 1:1.5.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        patients undergo elective surgery
      
Biospecimen description: 
      venous blood samples from patients undergo elective surgery with general anesthesia and
      mechanical ventilation
    
Keywords: R-spondin proteins, mechanical ventilation, lung injury