Clinical trial NCT03315702: Effect of Mechanical Ventilation on Plasma Concentration Level of R-spondin Proteins
Official title: the Change of R-spondin Proteins Plasma Concentration Level Caused by Mechanical Ventilation and Its Effect on Mechanical Ventilation Induced Lung Injury
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Lung Injury
Keywords: R-spondin proteins, mechanical ventilation, lung injury
Lead sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2017-10-20
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patients undergo elective surgery

Brief 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.

Eligibility criteria: Inclusion Criteria:

* undergo elective surgery with mechanical ventilation lasting for \> 3 hours; classified as physical status I to III according to the American Society of Anesthesiologists Physical Status Classification System; Written informed consent is approved.

Exclusion Criteria:

* chronic lung disease; recent lung infection; recent anaesthetics or mechanical ventilation treatment; hemodilution with massive fluid supply during surgery; children；women during pregnancy or lactation; being involved in other clinical subjects

Primary outcomes:
measure: Change in Plasma Concentration of R-spondin 1
timeFrame: 3 hours
measure: Change in Plasma Concentration of R-spondin 2
timeFrame: 3 hours
measure: Change in Plasma Concentration of R-spondin3
timeFrame: 3 hours
measure: Change in Plasma Concentration of R-spondin4
timeFrame: 3 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Department of Anesthesia, Shanghai Xinhua hospital
state: Shanghai
Study officials:
affiliation: Xinhua Hospital affiliated to Medicine school,Shanghai Jiaotong University
name: Lai Jiang, chief doctor
role: STUDY_CHAIR
References: