BMMSC-derived exosomes attenuate cardiopulmonary bypass-related acute lung injury by reducing inflammatory response and oxidative stress
BMMSC-derived exosomes attenuate cardiopulmonary bypass-related acute lung injury by reducing inflammatory response and oxidative stress
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DOI：
10.2174/1574888x17666220822123643
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Chong Lei
中科院分区：
文献类型：
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作者：
Tao-Yuan Zhang;Hui Zhang;Jing-Yu Deng;Hai-Rong Gong;Yun Yan;Zheng Zhang;Chong Lei
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 aims to evaluate the effects of BMMSC-Exo on post-CPB ALI and explored 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.
