Protective Effect Of Mitochondrial ATP-sensitive Potassium Channel On Lung Injury Induced By Hyperoxia In Premature Rats

Objective: To explore the protective effect of mitochondrialATP-sensitive potassium channel (mitoKATP) on lung injury induced byhyperoxia in premature rats.Methods:72Wistar premature rats were randomly divided intocontrol, hyperoxia and diazoxide group. The diazoxide group wasintraperitonealed with diazoxide (10mg/kg) before30min exposured inthe high oxygen. The others were treated with the same dose ofphysiological saline at the same time. The hyperoxia and diazoxide groupwere exposed to95﹪oxygen, while the control group were exposed to air.The rats in each group were sacrificed at1、3、7days after hyperoxiainduction and the lung tissues were collected. The histopathologicalchange of the lungs was observed by HE staining. Terminaldeoxynuleotidyl-mediated nick end labeling (TUNEL) was used to detectthe cell apoptosis index of lung issue. The expression of Omi/HtrA2、caspase-9and XIAP in lung issuse were evaluated byimmunohistochemisty. The translocation rate of omi/HtrA2in lung cellwere determined by indirect Immunofluorescence and observed with laserfocal microscope. Results: The lung tissue of d1、d3and d7showed no apparentinflammatory changes, and the alveolar structure gradually matured.Compared with controls, the lung of hyperoxia group are obviouslydamaged, which showed vascular congestion expansion, the red and theinflammatory cell infiltration, the alveolar interval thickening, the stromacollagen hyperplasia, the alveolar structure simplicity and the vesicles,alveolar atrophy and atelectasis. The apoptosis rate of lung cells(d1:25.02±4.48vs12.30±1.19, d3:43.96±2.76vs13.83±1.33, d7:56.78±2.23vs12.56±1.29), the expression of Omi/HtrA2(d1:9.72±0.89vs5.06±1.04, d3:11.08±1.73vs5.26±1.90, d7:13.32±1.12vs6.46±1.45, caspase-9(d1:10.13±0.77vs5.55±0.53, d3:12.66±0.61vs5.11±1.27, d7:14.58±0.46vs5.05±1.12) and the translocation rate Of Omi/HtrA2(d1:23.84±2.20vs5.75±0.82, d3:43.04±2.36vs8.11±0.94, d7:54.19±2.87vs8.85±0.72)weresignificantly increased, and the expression of XIAP was abviouslydecreased in the hyperoxia group compared with the control. Butcompared with the hyperoxia group, the morphology of lung tissue wereobviously alleviated serious in the diazoxide group. The apoptotis rateof lung cells (d1:19.82±3.16, d3:31.75±2.39, d7:37.93±2.56), theexpression of Omi/HtrA2(d1:7.59±0.40, d3:8.37±0.45, d7:9.23±0.27),caspase-9(d1:8.31±0.39, d3:10.32±0.50, d7:12.61±0.41), and thetranslocation rate of Omi/HtrA2(d1:18.40±1.90, d3:38.44±0.94, d7:40.04±1.28) were significantly reduced, the expression of XIAP(d1:5.83±0.39, d3:4.95±0.16, d7:3.87±0.44）was abviously increased in the diazoxidegroup(p<0.01).Conclusions: Diazoxide could relived the lung injury induced byhyperoxia via activating the mitoKATPreducing the expression ofOmi/HtrA2and caspase-9. It could relived the apoptosis index of alveolarepithelial cells by inhibiting the translocation of Omi/HtrA2frommitochondria.