Page 8 - GTM-2-3

Global Translational Medicine Hydrogen for acute lung injury

interstitial and alveolar edema, with a mortality rate to investigate the differences in treatment between 2% H
2
of 30 – 40% [1,2] . Injured lung tissues experience the and hydrogen saline, aiming to guide future ALI clinical
destruction of the alveolar epithelial and endothelial trials and clinical practice. We hypothesize that hydrogen
barriers, causing the deactivation of the alveolar surfactant therapy may play a role in repairing the alveolar barrier,
layer and an increase in lung interstitium permeability . eliminating excessive oxygen free radicals, and reducing
[3]
This allows the transfer of tissue fluid and hemoglobin the release of anti-inflammatory factors in ALI.
into the pulmonary interstitium and alveoli, resulting
in a reduction of lung compliance and obstruction of 2. Materials and methods
gas exchange . In addition, various factors that cause
[4]
injuries, such as bacterial toxins and mechanical stress, 2.1. Protocol registration
can induce inflammation, impairing the epithelium and The Preferred Reporting Items for Systematic Reviews
endothelium, promoting the migration of neutrophils, and Meta-analysis (PRISMA) 2020 reporting guidelines
and releasing inflammatory factors [2,4,5] . At present, a wide were used for this preclinical systematic review and
range of treatment strategies has been developed to address meta-analysis . We have preregistered a protocol on the
[15]
ALI, including glucocorticoid therapy, extracorporeal International Prospective Register of Systematic Reviews
membrane oxygenation (ECMO), and various supportive (PROSPERO) website. (https://www.crd.york.ac.uk/
interventions and drug therapies [6,7] . These interventions PROSPERO/, Registration number: CRD42021247370).
prevent further deterioration of ALI and play a therapeutic In response to the question, “Whether treatment effects
role. However, due to the heterogeneity of ALI, definitive between 2% H and hydrogen saline differ significantly
conclusions regarding the clinical application and in animal models of ALI?” we employed the sub-group
2
mechanism of these therapies are still lacking [6-8] .
analysis method to analyze the five relevant indicators
As a small molecule, hydrogen has a simple structure, within the groups of 2% H and hydrogen saline.
2
low molecular weight, and easy diffusion characteristics, To address the regional and national database
which enable it to easily access lung tissues . Recent
[9]
studies have highlighted its potential as a therapeutic limitations, the present paper used Fisher’s exact test
measure for ALI, attributed to its anti-inflammatory and to analyze the association between the language of the
antioxidant effects [10,11] . So far, hydrogen therapy for ALI included studies (Chinese and English) and their respective
includes two methods: inhalation of hydrogen gas and results.
injection of hydrogen saline . Inhaling hydrogen gas has 2.2. Search strategy and study selection
[11]
been shown to improve respiratory function and repair
the lung barrier in C57BL/6 mice . Similarly, injecting We conducted a comprehensive search for preclinical trials
[12]
hydrogen saline has been found to exert protective investigating the effect of hydrogen on ALI in various
effects on the alveolar epithelium and prevent surfactant electric databases, including PubMed, EMBASE, CNKI,
deactivation in Sprague-Dawley (SD) rats by inhibiting and Web of Science. The search encompassed studies
excessive autophagy . Moreover, hydrogen has been published through March 28, 2021. We used the PubMed
[13]
shown to inhibit the release of adhesion molecules and search strategy to ensure that all relevant studies were
inflammatory factors, thereby reducing endothelial included. Furthermore, the reference lists of the selected
damage, excessive endothelial permeability, and restoring papers were manually screened to identify any additional
lung tension to facilitate improved gas exchange after eligible studies.
neutrophil migration following alveolar damage . 2.2.1. Inclusion criteria
[14]
Despite the promising results, hydrogen therapy is still
in the preclinical trial stage, and a comparative study of The inclusion criteria are as follows:
the therapeutic effects between the two methods has not (i) Types: Studies involved animals with induced ALI.
been conducted. Exploring the differences in intervention (ii) Intervention: 2% H inhalation or injection of
2
measures can provide valuable insights into their impact hydrogen saline, and unlimited treatment times.
on the treatment of ALI. (iii) Control: Group(s) given placebo or no treatment.
The purpose of this systematic review and meta- (iv) Outcomes:
analysis is to provide a comprehensive summary of the key (a) Primary outcomes: W/D ratio and arterial oxygen
findings on the effectiveness and mechanisms of hydrogen partial pressure (PaO ).
2
therapy in animal models of ALI, particularly focusing (b) Secondary outcomes: Malondialdehyde (MDA),
on the relationship between ALI and hydrogen under superoxide dismutase (SOD), and tumor necrosis
oxidative stress and inflammation. The review also aims factor-alpha (TNF-α).

Volume 2 Issue 3 (2023) 2 https://doi.org/10.36922/gtm.0379