Effects of Mandibular Advancement Device on Genioglossus of Rabbits in Obstructive Sleep Apnea Through PINK1/Parkin Pathway

ABSTRACT Background Early treatment of mandibular advancement device (MAD) reverses the abnormal changes resulting from obstructive sleep apnoea (OSA), but the underlying mechanism is not clear. We analysed the changes of genioglossus function before and after MAD treatment in OSA rabbits and explored the mechanism of mitochondrial autophagy. Methods Eighteen male New Zealand rabbits were randomised into three groups: the control group, Group OSA, and Group MAD. After successful modelling, all animals were induced sleep in supine positions for 4–6 h per day for 8 weeks. Cone beam computed tomography (CBCT) and polysomnography (PSG) were performed to record sleep conditions. The genioglossus contractile force and the levels of LC3‐I, LC3‐II, Beclin‐1, PINK1 and Parkin were detected in three groups. In vitro, C2C12 myoblast cells were cultured under normoxic or hypoxic conditions for 24 h, and then the changes in mitochondrial structure and accumulation of autolysosomes were detected by transmission electron microscopy (TEM). Results The contractile tension of the genioglossus in Group OSA was significantly lower than that in the control group. The ratio of LC3II/LC3I and the levels of Beclin‐1, PINK1 and Parkin were higher in Group OSA than that in the control group. And the abnormal changes were tended to be normal after MAD treatment. The mitochondrial structure was disrupted, and the number of autolysosomes increased in C2C12 after 24 h of hypoxia. Conclusions MAD treatment in male rabbits may decrease the contractile tension of the genioglossus and increase the level of mitochondrial autophagy caused by OSA. And the mechanism of mitochondrial autophagy was mediated by the PINK1/Parkin pathway in male rabbits.