Exosomes derived from bone marrow mesenchymal stem cells alleviate lung ischemia-reperfusion injury in rats through miRNA-335/ SIRT3 pathway

Lung ischemia-reperfusion injury (IRI) is a clinically challenging problem. Exosomes (EXOs) derived from bone marrow mesenchymal stem cells (BMSC-EXOs) can alleviate multiple organs IRI, but few reports on lung IRI. MiRNA-335 is a kind of miRNA in EXOs, which was also shown protective effects on lung IRI. This study hypothesizes that BMSC-EXOs might alleviate lung IRI through miRNA-335, and further to explore its mechanism. The Sprague-Dawley male rats were divided into sham, IRI, phosphate buffer saline (PBS), and EXO groups (n = 6). In the sham group, rats were underwent anesthesia without IRI model establishment. In the IRI, PBS, and EXO groups, rats were established lung IRI model and with no treatment, 30 mu l PBS, or 20 mu g EXOs (in 30 mu l PBS), respectively. The miRNA-335 inhibitor and miRNA-335 mimic processed EXOs were also given to observe the effects of miRNA-335. The oxidative index, lung static compliance, inflammation response, oxidative stress injury, apoptosis, and mitochondrial were observed. The expression of miRNA-335 and silent matching type information regulation 2 homolog 3 (SIRT3) were also detected. The oxidative index, lung static compliance, inflammation response, oxidative stress injury, apoptosis, and mitochondrial injury were significantly deteriorated in the IRI group compared with those in the sham group, while those indicators have significantly improved in the EXO group, and the miRNA-335 and SIRT3 expressions increased (P < 0.05). And the miRNA-335 inhibitor processed EXOs suppressed the SIRT3 expression significantly, but the miRNA-335 mimic processed EXOs enhanced the SIRT3 expression significantly (P < 0.05). In conclusion, BMSC-EXOs maintained mitochondrial structural stability, and alleviated rat lung IRI by inhibiting lung inflammation, oxidative stress injury, and apoptosis, improved lung oxygenation capacity and static compliance, which might be achieved through the miRNA335/SIRT3 pathway.