Adenosine A2a receptor agonist CGS21680 treatment attenuates cardiopulmonary bypass‑associated inflammatory lung injury in juvenile rats

Kong,Xiang; Zuo,Yi; Huang,Yu'ang; Ge,Jianjun

doi:10.3892/mmr.2019.10235

Adenosine A2a receptor agonist CGS21680 treatment attenuates cardiopulmonary bypass‑associated inflammatory lung injury in juvenile rats

Authors:
- Xiang Kong
- Yi Zuo
- Yu'ang Huang
- Jianjun Ge
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Affiliations: Department of Cardiovascular Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (USTC), Hefei, Anhui 230001, P.R. China
Published online on: May 14, 2019 https://doi.org/10.3892/mmr.2019.10235
Pages: 117-124

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Abstract

The adenosine A2a receptor agonist CGS21680 has been suggested to act as an anti‑inflammatory agent that protects against cardiopulmonary bypass (CPB)‑induced organ injury. However, the therapeutic effects of CGS21680 for CPB‑induced lung injury have not been comprehensively evaluated. Using a juvenile rat model, the present study was designed to evaluated whether CGS21680 attenuates CPB‑induced lung injury. Our juvenile rat CPB model was established by 60 min CPB with or without CGS21680 pretreatment (100 µg/kg, in the CPB priming solution). Rats in the Sham group only underwent cannulation and heparinization. Serum and pulmonary levels of inflammatory markers and histological features of pulmonary tissues were analyzed. All juvenile rats survived following CPB. Significantly elevated serum levels of tumor necrosis factor‑α (TNF‑α), myeloperoxidase (MPO) and interleukin‑1β (IL‑1β), and decreased glutathione peroxidase (GSH‑PX) levels were observed in the CPB group compared to the Sham group (all P<0.05). TNF‑α, MPO and IL‑1β were significantly decreased, while GSH‑PX was markedly increased in the CGS group when compared to the CPB group. Consistently, pulmonary tissues from rats in the CPB group showed considerable amounts of damaged pneumocytes, severe edema, and increased alveolar macrophages, and significantly higher lung injury scores compared to the controls. Collectively, these changes were all further attenuated by CGS21680. Pretreatment with CGS21680 before CPB attenuated pulmonary injury, which may be related to the anti‑inflammatory effects of CGS21680 downstream of A2a receptor activation.

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