Protective Effect Of Ucf-101on Lung Injury Induced By Hyperoxia In Premature Rats

Objective To explore protective effect of specific inhibitor of Omi/HtrA2(Ucf-101) on lung injury induced by hyperoxia in premature rats.Methods72Wistar premature rats were randomly divided into control,hyperoxia and hyperoxia+Ucf-101group. The hyperoxia+Ucf-101group wasinjected with Ucf-101(1.5μmol/kg) intraperitoneally at10min before hyperoxiainduction. The others were treated with the same dose of physiological saline atthe same time. The hyperoxia group and hyperoxia+Ucf-101group wereexposed to95﹪oxygen, while control group were exposed to air. The rats ineach group were sacrificed at1,3,7days after being exposed to hyperoxia orair and the lung tissues were collected. The left lung tissues were made intoparaffin–embedded slices.The histopathological changes of the lungs were observed by hematoxylin and eosin staining(HE),Streptavidin-peroxidaseimmunohistochemistry was used to detect the expression of Omi/HtrA2、XIAPand Caspase-9in the lung cells of each group, terminal transfer nick endlabeling (TUNEL) was used to detect the apoptosis of lung issue cells; Theright lung tissues were made into cryopreserved slices, the translocation rate ofOmi/HtrA2was determined by indirect immunofluorescent double stainingmethod and observed with laser confocal microscope.Results (1) The lung tissues of the control groupd exposed to1,3,7daysgradually matured,which the alveolar structure developed to normalizedgradually and the alveolar septum thinned. Compared with control group, ratsin hyperoxia group showed typical lung injury,which was characterized byalveolitis and delayed of luny development. While pulmonary pathologicchanges were alleviated in hyperoxia+Ucf-101group compared withhyperoxia group.(2) The expression of Omi/HtrA2and Caspase-9of lungtissues both significantly increased in hyperoxia group and hyperoxia+Ucf-101group compared with control group(P<0.05),While the expression ofOmi/HtrA2and Caspase-9of lung tissues in hyperoxia+Ucf-101group waslower than that in hyperoxia group(P<0.01).The expression of XIAP in controlgroup was higher than that in the other groups (P <0.01),While the expressionof XIAP in hyperoxia+Ucf-101group was significantly higher than inhyperoxia group at the same time point(P<0.01).(2)The apoptotic index oflung tissue cells were higher in hyperoxia group and hyperoxia+Ucf-101group than that in control group (P<0.01),while the apoptotic index ofhyperoxia+Ucf-101group was lower than that in hyperoxia group at the sametime point(P<0.01).(3) Compared with control group, thetranslocation rate of Omi/HtrA2were significantly increasing in hyperoxiagroup and hyperoxia+Ucf-101group (P<0.01).While the translocationrate of Omi/HtrA2of hyperoxia+Ucf-101group were significantly decreasingthan that in hyperoxia group at the same time point (P<0.01).Conclusion Ucf-101could inhibit apoptosis of lung cells to alleviatehyperoxia-induced lung injury of premature rats through reducing theexpression of Omi/HtrA2and inhibiting the translocation of Omi/HtrA2frommitochondria.