Study Of The Protective Mechanism Of Dexmedetomidine In Hyperoxic Lung Injury Model Mice At The Mitochondrial Level

Objective:The purpose of this study was to investigatethe damage of mitochondria in lung tissue by hyperoxic conditions and the self-protective effect of mitophagy.Through animal experiments,to define the protective effect of dexmedetomidine in neonatal rats at the mitochondrial level,which provides new ideas for the clinical treatment and prognosis improvement of hyperoxic lung injury.Methods:SPF healthy SD pregnant rats were randomly divided into four groups（n=6）:air control group（Group A）,hyperoxia injury group（Group B）,dexmedetomidine（Dex）control group（Group C）,and hyperoxia+Dex group（Group D）,Groups A and C were exposed to 21%O₂,Groups B and D were exposed to 90%O₂.Among them,group B and group D were gave a daily intraperitoneal injection of Dex 500μg/kg.Lung tissue specimens were collected 7 days after modeling.Lung morphological changes were observed by hematoxylin-eosin staining,to assess the molding condition.Transmission electron microscopy was used to observe mitochondrial ultrastructural changes in type I epithelial cells of neonatal rat lung tissue cells.To determine the Complex I activity in neonatal rat lung tissue.RNA was extracted from neonatal rat lung tissue,and after reverse transcription,PCR amplification and assessed by Real-time quantitative polymerase chain reaction（q PCR）,to assess Parkin and PINK 1 expression in neonatal rat lung tissue.The protein expression levels of PINK 1 and Parkin in lung tissues were determined using Western blot technology.Results:HE staining showed the same alveolar structure of group A and group C,with clear cytoplasm and nucleus and uniform distribution.In group B,the alveolar wall became thin and heterogeneous,some alveolar space fused,the alveolar number decreased,the structure tends to simplify,and some pulmonary septum was significantly thickened,accompanied by vascular dilation,stromal hyperplasia and fibrotic proliferation.Compared with group B,the alveolar number in group D increased and the thickness of alveolar septum decreased.Under TEM,the mitochondria in group A and group C lung tissue were intact,with bilayer membrane structure and clearly visible crest.Group B mitochondrial structure damage,wrinkled,vacuolization and cristae disappearance.In group D,compared with group B,some mitochondrial bilayers and cristae existed,but some mitochondria were vacuolated.The Complex I activity in neonatal rat lung tissue was significantly lower in group B than in group A（P<0.05）,and compared with group B,the Complex I activity was significantly higher in group D（P<0.05）.According to the q PCR of PINK1 and Parkin in neonatal rat lung tissue,compared with group A,PINK1 and Parkin expression were significantly increased in group B（P<0.05）.And compared with group B,PINK1 and Parkin were more expressed in group D（P<0.05）.Western blot to test the protein expression levels of PINK 1 and Parkin in the lung tissue of neonatal rats,compared with group A,the expression of PINK 1 and Parkin was significantly increased in group B（P<0.05）.Compared with group B,the expression of PINK 1 and Parkin was higher in group D（P<0.05）.Conclusions:The application of Dex in neonatal rats with hyperoxic lung injury can effectively reduce the destruction of mitochondrial ultrastructure,increase the activity of Complex I in the oxidized respiratory chain in their mitochondria,and activate the PINK 1-Parkin mediated mitophagy pathway,increase the level of mitophagy,and reduce the mitochondria damage of hyperoxia on lung tissue in neonatal rats.