Abstract

ObjectiveTo evaluate the effects of doxofylline on inflammatory responses and oxidative stress during mechanical ventilation in rats with chronic obstructive pulmonary disease (COPD).MethodsEight-week-old male Sprague Dawley rats were selected, and the COPD rat model was constructed. The rats were randomly divided into a model group (group M), a model + normal saline group (group N), a doxofylline group (group D), and a control group fed with conventional chow and given normal oxygen supply (group C) (n = 12 in each group). Tracheal intubation and mechanical ventilation were conducted in the rats in each group after anesthesia. A real-time intravenous infusion with 50 mg/kg of doxofylline was conducted in group D, and there was no drug intervention in groups C, N and M. Pathological manifestations of the pulmonary tissues were observed and compared among the groups. And some indicators were evaluated.Results(1) The pulmonary tissues of the rats in groups M, N, and D exhibited typical pathological histological changes of COPD. (2) Groups M, N, and D showed increased Ppeak, PaCO2, total white blood cell count in BALF, and IL-8, TNF-α, and MDA levels in the pulmonary tissue and BALF, and decreased PaO2 and IL-10 and SOD levels, compared with group C. (3). Group D showed decreased Ppeak, PaCO2, total white blood cell count in BALF, and IL-8, TNF-α, and MDA levels in the pulmonary tissue, and increased PaO2 and IL-10 and SOD levels, compared with group N or M.ConclusionDoxofylline was shown to improve ventilation and air exchange during mechanical ventilation in rats with COPD, reduce the inflammatory response and oxidative stress, and mitigate the degree of pulmonary tissue injury.

Highlights

  • Doxofylline is a methylxanthine derivative of a phosphodiesterase inhibitor, and, as a new type of theophylline, it has been proven to exhibit superior pharmacologicalChen et al BMC Pulmonary Medicine (2022) 22:66 smooth muscle, strengthen diaphragm contraction, and help improve the pulmonary ventilation function [3].Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease, characterized by airflow limitation that is not fully reversible

  • General characteristics and histopathological manifestations of rats in each group The rats in group C were in better general condition than those in the COPD model: they were more lively and active, and showed better hair luster, smooth and regular respiration, and rapid weight gain

  • The ideal animal COPD model should have common etiologies consistent with human disease and histopathological changes characterized by airway remodeling and emphysematous pathology, which should be consistent with clinical practice

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Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease, characterized by airflow limitation that is not fully reversible. The condition may be progressive and is correlated with abnormal chronic inflammation of the airways and pulmonary tissue in response to harmful gases or particles such as cigarette smoke. The main pathophysiological change is persistent airflow restriction, leading to pulmonary ventilation dysfunction. With the development of COPD, dysfunction of ventilation and air exchange may cause hypoxia and carbon dioxide retention, and eventually lead to respiratory failure [4]. Protease/anti-protease imbalance, and oxidative and antioxidant imbalance are all involved in the pathogenesis of COPD [5, 6]. Mechanical ventilation during surgical anesthesia tends to result in elevated airway pressures, causing an imbalance in the ventilation/blood flow ratio in the lungs and a release of inflammatory mediators

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