The Effects Of Endoplasmic Reticulum Stress In The Process Of Hyperoxia-induced Lung Injury In Premature Rats

Objective To explore the effects of endoplasmic reticulum (ER) stress inthe process of hyperoxia-induced lung injury in premature rats.Methods Forty-eight premature Wistar rats were randomized into twogroups12hours after born: hyperoxia group (24rats) inhaled with95%oxygen;control group (24rats) inhaled with21%oxygen. Eight rats were sacrificed ineach group on day1,3,7after the treatment and the left lungs were embedded.HE staining was performed to observe the pathological changes of lung tissues,while immunohistochemistry (streptavidin-peroxidase,SP method) was appliedto detect the expressions of ER related protein ERp57and c/EBP homologousprotein CHOP. The apoptosis of lung cells were also detected by TUNELanalysis.Results (1) Pathological changes of lung tissue: under light microscope,the structures of lung tissue in the control group were normal. While forhyperoxia group, there were many large irregular alveoli on day1, revealing nosignificant difference. However, the microvessels were dilated, alveolarepithelia were swelling and the alveolar and interstitial spaces were filled withmassive red blood cells and inflammatory cells on day3, and all these changeswere more remarkable on day7.(2) The expression and distribution of ERp57and CHOP in lung tissue: ERp57and CHOP were widely expressed in the cytoplasm of alveolar epithelial cells, bronchial epithelial cells and vascularendothelial cells. The ERp57and CHOP were weekly expressed in controlgroup, and were significantly higher in hyperoxia group. Besides, theexpressions of ERp57and CHOP increased with the exposure time inhyperoxia (AOD of ERp57: control group, d1,0.235±0.023; d3,0.257±0.056;d7,0.267±0.058; hyperoxia group, d1,0.320±0.026; d3,0.347±0.054; d7,0.400±0.027, P <0.05. AOD of CHOP: control group, d1,0.165±0.037; d3,0.268±0.036; d7,0.207±0.034; hyperoxia group, d1,0.307±0.048; d3,0.318±0.063; d7,0.330±0.054, P <0.05).(3) TUNEL analysis: there were fewpositive cells in control group; however, the apoptosis rates of lung cells weresignificantly higher in hyperoxia group, and were increased with the exposuretime in hyperoxia (Apoptotic index, AI: control group, d1,14.44±1.10; d3,14.60±2.06; d7,14.35±1.45; hyperoxia group, d1,25.49±1.25; d3,44.97±1.82; d7,55.34±1.76, P <0.01；（4）The relationship between cell apoptosisindex and expressions of Erp57and c/EBP homogeneous protein analyzed bylinear correlation analysis: For cell apoptosis index and ERp57, R=0.789andP<0.01; while for cell apoptosis index and c/EBP homogeneous protein,R=0.645and P<0.01. The results indicated significant positive correlation.Conclusions (1) The exposure of premature rats in hyperoxia could resultin acute lung injury, and it’s increased with the exposure time.(2) Theexpressions of ERp57and CHOP were increased in the lung tissue ofpremature rats exposed in hyperoxia, indicating ER stress initiated apoptosis played an important role in the process of hyperoxia-induced lung injury inpremature rats. However, the potential mechanism needs further studies.(3)The expressions of ERp57and CHOP were correlated with dynamic changes ofapoptotic index.