Prasugrel ameliorates seawater aspiration-induced acute lung injury in rats by inhibiting adhesion of platelets and neutrophils

Abstract

Objective To observe the protective effect of Prasugrel on seawater aspiration-induced acute lung injury of SD rats and explore the possible mechanisms. Methods Seawater was instilled into the airway of SD rats. The rats were observed after 1 h or 2 h once acute lung injury was conducted. Then the rats were randomly divided into 3 experimental groups (n=8 in each group): seawater group, solvent sodium carboxmethylcellulose (CMC-Na) group and Prasugrel group. Other 8 healthy SD rats were taken as the normal control group. The rats were treated with CMC-Na solution or Prasugrel 4 h before seawater inhalation by intragastric administration in the CMC-Na group and Prasugrel group, respectively. Histological examination, measurements of wet to dry weight ratio of the lung samples, the expression of inflammatory cytokines and the protein concentration and myeloperoxidase (MPO) activity of the bronchoalveolar lavage fluid (BALF) were carried out after modeling. And the adhesion of the platelets with neutrophils was measured by flow cytometry. Results Compared with the normal control group, the inflammation and edema of the lung tissues were obvious in the three experimental groups. The sections of hematoxylin-eosin staining showed that the alveolar architecture distortion, pulmonary edema, interstitial thickening and infiltration of the inflammatory cells in the lung tissues were evident after seawater instillation. And the expression levels of TNF-α, IL-1β and TXB2 in the plasma measured by ELISA increased after seawater stimulation, as well as the protein concentration and MPO activity of BALF. The adhesion of platelets and neutrophils increased significantly. Meanwhile, the damage was more severe 2 h after seawater stimulation. However, pretreatment of Prasugrel attenuated the lung inflammation and edema, decreased the release of inflammatory factors, and inhibited the adhesion of platelets and neutrophils. Conclusion The adhesion of platelets and neutrophils after seawater aspiration-induced acute lung injury is increased notably. Prasugrel ameliorates the injury and reveals a remarkable protective effect by inhibiting the adhesion of platelets and neutrophils probably. Key words: Acute lung injury; Seawater; Prasugrel; Platelets; Neutrophils