The Intervention Effect Of Edaravone Combined With Mechanical Ventilation Onlung Injury And Brain Damage Of Hydrochloric Acid Induced Acute Lung Injury Rats Model

Background and ObjectivesMechanical ventilation is an effective treatment for ALI/ARDS, it can reduce mortality of ALI/ARDS significantly. However, the application of mechanical ventilation with excessive Vidal capacity may increase alveolar capillary permeability and lung injury (VILI), which will lead to increasing patient mortality. Several studies focus on pathogenesis of ALI/ARDS and protective ventilation strategy and drug treatment have been established in recent years, which may decrease the severity of ALI/ARDS, but not satisfied outcomes as expected. Hence different strategies of mechanical ventilation and protective effect of preventive drugs should be studied in depth. ALI/ARDS patients who admitted in ICU were always combined with neuropsychological changes and cognitive, memory ability of these patients were significantly diminished,so researchers and clinicians starts to pay attention to "Lungs-brain interaction".Edaravone is a kind of anti-oxidant drug with anti-inflammatory effect. Edaravone has been demonstrated its protective role to lung injury and brain damage by scavenging free radicals. In this study, rats were given intratracheal instillation with hydrochloric acid joint with high or low tidal volume ventilation.this study aimed to explore effect and mechanism of different ventilation strategies to lung injury and brain injury of ALI/ARDS, edaravone intervention were also established in this model, which aimed to discover combination therapy of ARDS from the perspective of preventive drugs.Results and conclusions1. ARDS rats model were established successfully by using mechanical ventilation combined hydrochloric acid, combined with brain damage。 This model showed oxidative stress action and metabolic disorders and inflammatory responses and especially in groups with tidal volume group.2. Edaravone can protect lung and brain tissue of ARDS rats from peroxidation and metabolic disorders, it can also inhibit inflammation.Chapter Ⅰ:Effect of Edaravone combined with mechanical ventilation on lungs of hydrochloric acid induced acute lung injury rats modelAimsThis study aims to explore effect of different ventilation strategies on pathology, biochemistry and inflammatory indexes of lungs of ARDS rats, and compare the effect of edaravone intervention.Methods70 SD rats were divided into seven groups:control group (normal control), HV group (High Vidal capacity:HV), LV group (Low Vidal capacity:LV), HV+HCL group (High+hydrochloric acid:HV+HCl), LV+ HCL group (Low Vidal capacity +hydrochloric acid:LV+HCl), HV+HCl+edaravon group (HV+HCl group was given edaravone), LV+HCl+edaravon group (LV+HCl group received edaravone). Before anesthesia HV+HCl+edaravon, LV+HCl+edaravon groups were injected edaravone liquid from the tail. After anesthesia ARDS model were established by injecting hydrochloride through the trachea and mechanical ventilation, ventilation volume of HV group was 15mL/kg, PEEP was 0cmH2O, ventilation volume of LV group was 6ml/kg, PEEP was 3cmH2O. animals were killed after 6 hours continuous ventilation. Neutrophils count in bronchoalveolar lavage fluid (BAL) were counted by using Wright’s staining, lung injury score were recorded by tissues HE staining of lung tissue, MPO, GSH, Na+-K+-ATP activity, MIP2, TNF-a were detected in lung tissue and BAL, NSE and GABA (A) a2 Receptor expression were detected by using immunohistochemistry.Results and conclusionsFrom pathology observation and lung injury score HE staining, Mechanical ventilation showed lung injury effect and edaravone showed protective effect. All treatments groups showed significantly changes in all measurements compared to blank control group. High vidal capacity group showed higher inflammatory effect and oxidative stress compared to low vidal compacity group. Edaravone intervention group showed protective effect in reducing inflammatory cytokines release and reducing oxidative stress in lungs.Chapter Ⅱ:Effect of Edaravone combined with mechanical ventilation on brains of hydrochloric acid induced acute lung injury rats modelAimsThis study aims to explore effect of different ventilation strategies on pathology, biochemistry and inflammatory indexes of brains of ARDS rats, and compare the effect of edaravone intervention.MethodMethodology of animal model establishment was same as chapter one, The pathology change of brain tissue of rats were observed by HE staining, GSH, Na+-K +-ATP activity, MIP2, TNF-a, IL-6, S-100β, NSE were detected in samples from brain, S-100β, NSE expression were detected by using immunohistochemistry.Results and conclusionFrom pathology observation and HE staining, there were no differences between HV group and LV group, nor between edaravone intervention group and its corresponding group. HV group showed higher inflammatory effect and oxidative stress compared to LV group in TNF-a, IL-6, GSH, NSE, MIP-2, S100-beta detecting. Edaravone intervention group showed protective effect in reducing inflammatory cytokines release and reducing oxidative stress in all measurements. So mechanical ventilation may result in brain damage especially in high vidal capacity ventilation, and edaravone showed protective effect on brain injury of ARDS.