Title:BMMSC-derived Exosomes Attenuate Cardiopulmonary Bypass-related
Acute Lung Injury by Reducing Inflammatory Response and Oxidative
Stress
Volume: 18
Issue: 5
Author(s): Tao-Yuan Zhang, Hui Zhang, Jing-Yu Deng, Hai-Rong Gong, Yun Yan, Zheng Zhang*Chong Lei*
Affiliation:
- Department of Cardiology, PLA Rocket Force Characteristic Medical Center,
Beijing 100088, China
- Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Air Force Medical University,
Xi'an, Shaanxi, 710032, China
Keywords:
Acute lung injury, bone marrow mesenchymal stem cells, cardiopulmonary bypass, exosomes, inflammation, oxidative stress.
Abstract:
Background: Acute lung injury (ALI), which is characterized by inflammation and oxidative
stress, is a common complication after cardiopulmonary bypass (CPB). Exosomes from bone marrow
mesenchymal stem cells (BMMSC-Exo) have recently been identified as promising treatments for ALI.
However, the effects of BMMSC-Exo on inflammation and oxidative stress in CPB-related ALI remain
unclear.
Objective: We aim to evaluate the effects of BMMSC-Exo on post-CPB ALI and explore their potential
mechanisms.
Methods: We randomly divided rats into three groups: sham, ALI, and ALI+BMMSC-Exo groups. Histological
changes were evaluated by lung histo-pathology and bronchoalveolar lavage fluid (BALF). ELISA
assay was used to determine inflammatory cytokine levels and oxidative stress.
Results and Discussion: BMMSC-Exo attenuated histological changes (including the invasion of inflammatory
cells), reduced the wet/dry (W/D) weight ratio, and downregulated inflammatory cytokine
levels, including tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-1β. BMMSC-Exo also
alleviated oxidative stress. In vitro, we further administered lipopolysaccharide (LPS) to alveolar macrophages
(AMs) to mimic the pathological changes of ALI and found that BMMSC-Exo suppressed reactive
oxygen species (ROS) production and downregulated the levels of inflammatory cytokines. Mechanistically,
BMMSC-Exo inhibited the phosphorylation of nuclear factor-κB (NF-κB), the nuclear translocation
of p65, also facilitated the phosphorylation of Akt and the nuclear translocation of Nrf2, while
upregulating the expression of HO-1.
Conclusion: In summary, we indicate that BMMSC-Exo reduces CPB-related ALI by alleviating inflammation
and oxidative stress. The underlying mechanism may involve the NF-κB p65 and
Akt/Nrf2/HO-1 signaling pathways.
