Diannexin Can Ameliorate Acute Respiratory Distress Syndrome in Rats by Promoting Heme Oxygenase-1 Expression.

Ying-Nan Ju,Wei Gao,Hai-Bin Sun,Xiao-Qing Zhao,Guang-Xiao Xu,Qi-Hang Tai,Andreas Ludwig

doi:10.1155/2021/1946384

Abstract

Background The recombinant protein diannexin can inhibit platelet-mediated events, which contribute to acute respiratory distress syndrome (ARDS). Here, we investigated the effect of diannexin and its effect on heme oxygenase-1 (HO-1) in ARDS. Methods A total of 32 rats were randomized into sham, ARDS, diannexin (D), and diannexin+HO-1 inhibitor (DH) groups. Alveolar-capillary permeability was evaluated by testing the partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio, lung wet/dry weight ratio, and protein levels in the lung. Inflammation was assessed by measuring cytokine levels in the bronchial alveolar lavage fluid (BALF) and serum and nuclear factor-κB (NF-κB) in the lung tissue. Inducible nitric oxide synthase (iNOS), malondialdehyde (MDA), and myeloperoxidase (MPO) were measured to evaluate the oxidative stress response. Lung tissue pathology and apoptosis were also evaluated. We measured HO-1 expression in the lung tissue to investigate the effect of diannexin on HO-1 in ARDS. Results Compared with the ARDS group, diannexin improved PaO2/FiO2, lung wet/dry weight ratio, and protein levels in the BALF and decreased levels of cytokines and NF-κB in the lung and serum. Diannexin inhibited the oxidative stress response and significantly ameliorated pathological lung injury and apoptosis. The partial reversal of diannexin effects by a HO-1 inhibitor suggests that diannexin may promote HO-1 expression to ameliorate ARDS. Conclusions We showed that diannexin can improve alveolar-capillary permeability, inhibit the oxidative stress response and inflammation, and protect against ARDS-induced lung injury and apoptosis.

Highlights

Acute respiratory distress syndrome (ARDS) is characterized by an increase in alveolar-vascular permeability, lung edema, and severe hypoxemia, leading to respiratory failure [1]
We observed a significant increase in apoptosis in the acute respiratory distress syndrome (ARDS) and diannexin+HO-1 inhibitor (DH) groups, but decreased apoptosis in the D group compared to the sham group (Figure 3)
In the D group, there was a decreased amount proapoptotic proteins and increased amount antiapoptotic proteins. This observation was reversed in the DH group, suggesting that ZNPP counteracts the cytoprotective effects of diannexin (Figure 4)

Summary

Background

The recombinant protein diannexin can inhibit platelet-mediated events, which contribute to acute respiratory distress syndrome (ARDS). Alveolar-capillary permeability was evaluated by testing the partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio, lung wet/dry weight ratio, and protein levels in the lung. Inflammation was assessed by measuring cytokine levels in the bronchial alveolar lavage fluid (BALF) and serum and nuclear factor-κB (NF-κB) in the lung tissue. We measured HO-1 expression in the lung tissue to investigate the effect of diannexin on HO-1 in ARDS. Compared with the ARDS group, diannexin improved PaO2/FiO2, lung wet/dry weight ratio, and protein levels in the BALF and decreased levels of cytokines and NF-κB in the lung and serum. Diannexin inhibited the oxidative stress response and significantly ameliorated pathological lung injury and apoptosis. We showed that diannexin can improve alveolar-capillary permeability, inhibit the oxidative stress response and inflammation, and protect against ARDS-induced lung injury and apoptosis

Introduction

Materials and Methods

Results

Discussion

Conclusions