Abstract | OBJECTIVE: This study aimed to determine whether high tidal volume (HTV) induce mitochondria damage and mitophagy, contributing to the release of mitochondrial DNA ( mtDNA). Another aim of the present study was to investigate the role and mechanism of mtDNA in ventilator-induced lung injury (VILI) in rats. METHODS: MAIN RESULTS: Rats subjected to HTV showed more severe pulmonary edema and inflammation than the other rats. The decreased expression of TLR9, MyD88, and NF-κB were observed following the use of ODN2088. Mechanical ventilation (MV) with HTV damaged mitochondria which resulted in dysfunctional ATP synthesis, accumulation of reactive oxygen species, and loss of mitochondrial membrane potential. Moreover, the results of distribution of fluorescence in rats upon HTV stimulation indicated that mtDNA cleavage was associated with mitophagy. The expression levels of mitophagy related genes (LC3B-II/LC3B-I, PINK1, Parkin, and mitofusin 1) in animals ventilated with HTV were significantly upregulated. Administration of antimycin A aggregated the histological changes and inflammation after MV, but these effects were attenuated when administered in the presence of cyclosporine A. CONCLUSION: MV with HTV induces mitochondrial damage and mitophagy, contributing to the release of mtDNA, which may be induced VILI in rat via TLR9/MyD88/NF-κB signaling pathway.
|
Authors | Jin-Yuan Lin, Ren Jing, Fei Lin, Wan-Yun Ge, Hui-Jun Dai, Linghui Pan |
Journal | Frontiers in immunology
(Front Immunol)
Vol. 9
Pg. 1477
( 2018)
ISSN: 1664-3224 [Print] Switzerland |
PMID | 30018615
(Publication Type: Journal Article)
|