Objective To study the effects of hyperoxia on ventilator-induced lung injury（VILI） in rats.Methods 48 healthy male SD rats were randomly divided into four groups：Group A received conventional mechanical ventilation（VT=8 mL/kg） with room air，Group B received the same tidal volume as group A with 100% O2，Group C received large tidal volume（VT=40 mL/kg） with room air，group D received the same tidal volume as group C with 100% O2.Arterial blood gases were measured every one hour and oxygenation index（PaO2/FiO2） was calculated.The changes of lung histopathology were assessed by HE staining and observed under light microscope.Wet-to-dry weight ratio（W/D） of left lung，neutrophils and white blood cell（WBC） counts in BALF were measured.TNF-α，IL-1β，and MIP-2 levels in BALF，malondialdehyde（MDA），myeloperoxidase（MPO），and superoxide dismutase（SOD） levels in the lung were assayed，respectively.Results Compared with the Group C，the Group D demonstrated more infiltrating neutrophils in the lung and more destructive changes in the alveolar wall.Meanwhile，the oxygenation index decreased，the WBC and neutrophils counts in BALF increased，and the W/D of left lung was higher in the Group D with significant differences compared with the Group C.Moreover，the BALF levels of TNF-α，IL-1β and MIP-2，the lung levels of MDA increased，and the lung levels of SOD decreased significantly in the Group D compared with those in the Group C.There were no statistical significant differences between the Group B and Group A in all parameters except that MDA levels increased and SOD levels decreased significantly in the Group B.Conclusion Hyperoxia can increase lung injury induced in large tidal volume ventilation in rats，but has mininmal effects in conventional mechanical ventilation.
Objective To explore the expression and effect of heme oxygenase-1 ( HO-1) in ventilator-induced lung injury. Methods Twenty-four New Zealand rabbits were randomly assigned to three groups, ie. a conventional ventilation + PEEP group( C group) , a ventilator-induced lung injury group( VILI group) , and a VILI + HO-1 inducer hemin group( Hm group) .Western blot and immunohistochemistry assay were used to investigate the expression of HO-1 protein. Blood gas analysis, lung wet /dry ratio, lunghistopathology and lung injury score were used to evaluate lung injury. Results HO-1 protein expression significantly increased in the VILI group compared with the C group. HO-1 was found mainly in alveolar epithelial cells and vascular endothelial cells, as well as in alveolar macrophages and neutrophils. Compared with the VILI group, HO-1 protein and PaO2 /FiO2 increased, while lung wet/dry ratio and lung injury score decreased in the Hmgroup significantly( P lt;0. 05) . Conclusion High HO-1 expression can alleviate lung injury from large tidal volume ventilation, implying its protective role in lung pathogenesis.
Ojective To establish a rat model of hyperoxia induced acute lung injury. Methods Eighty healthy male SD rats were randomly divided into an air group and a hyperoxia group ( ≥95% O2 ) .Each group was further divided into 12 h, 24 h, 36 h, 48 h, 60 h subgroups. Arterial blood gas was monitored. Lung tissue was sampled for evaluation of lung wet to dry ratio, lung index, and pulmonary permeation index. Bronchoalveolar lavage fluid ( BALF) was collected for measurement of lactatedehydrogenase ( LDH) activity and white blood cell count ( WBC) . Results After hyperoxia exposure for 48 ～60 h, lung pathology showed alveolar structure disruption, lung parenchyma wrath bleeding and edema.Lung wet to dry ratio, lung index, pulmonary permeation index, LDH and WBC in BALF all increased significantly, peaked at 48 h and remained at high level at 60 h while PaO2 dropped progressively.Conclusion Exposure to ≥ 95% O2 for 48 ～60 h can successfully establish the rat model of hyperoxia induced acute lung injury.
Objective To investigate the effects of recombinant human erythropoietin ( rHuEPO) on expressions of Bax and Bcl-2 proteins in hyperoxia-induced lung injury of adult rats. Methods Fortyeight healthy male SD adult rats were randomly divided into six groups. The control group ( 0 h) breathed with room air. The rHuEPO intervention group was put into oxygen chamber and breathed with 100% O2 for 96 h plus intraperitoneal injection of rHuEPO (1000 U/kg) daily. Other four groups were put into oxygen chamber and breathed with 100% O2 for 24, 48, 72 and 96 h respectively. Arterial blood gases were measured to calculate oxygenation index. Wet-to-dry weight ratios of left lung were measured. The contents of TNF-α and IL-1β in bronchoalveolar lavage fluid (BALF) were assayed with radioimmunoassay. The expressions of Bax and Bcl-2 proteins in the lung were determined withWestern blot and immunohistochemisty. The changes of lung histopathology were assessed by hematoxylin and eosin stain and observed under light microscope. Results After breathing 100% O2 , the oxygenation index decreased gradually and reached minimal value at 96 h. The wet-to-dry weight ratio of left lung increased gradually and reached maximal value at 96 h. The contents of TNF-α and IL-1β in BALF reached maximal value at 48 h and then decreased gradually. The expression of Bax protein increased, but the expression of Bcl-2 protein decreased gradually in the lung. Compared with the 96 h group, the oxygenation index was higher, wet-to-dry weight ratio and contents of TNF-α and IL-1β in BALF decreased, the expression of Bax protein decreased, and the expression of Bcl-2 protein increased in the lung of the rHuEPO group. Conclusion rHuEPO can attenuate hyperoxia-induced lung injury of adult rats by down-regulating expression of Bax protein and up-regulating expression of Bcl-2 protein.
Objective To establish a rabbit model of ventilator-induced lung injury. Methods Fourty healthy New Zealand rabbits were randomly divided into 3 groups: ie. a routine 8 mL/kg tidal volume group( VT8 group) , 25 mL/kg large tidal volume group( VT25 group) , and 40 mL/kg large tidal volume group( VT40 group) . VT25 and VT40 group were further divided into 2 hours and 4 hours ventilation subgroups. Arterial blood gas, lung mechanical force and hemodynamic parameters were monitored. Lungtissue was sampled for evaluate lung wet/dry ratio and lung injury by HE stain. Bronchoalveolar lavage fluid ( BALF) was collected for measurement of protein concentration, total and differential cell counts. Results Compared with VT8 group, lung injury score in both VT40 and VT25 groups were elevated significantly, ofwhich 4 hour VT40 subgroup was the highest. Lung pathology examination of VT40 group revealed apparent alveolar deformation, interstitial and alveolar space exudation, inflammatory cells infiltration, pulmonary consolidation and alveolar hemorrhage. Lung pathology examination of VT25 group showed pulmonary intervalthickening, inflammatory cells infiltration, while alveolar intravasation was mild. Blood gas analysis showed that PaO2 /FiO2 was deteriorated with time in VT25 and VT40 groups, and PaO2 /FiO2 at the 3 hours in VT40 group( lt; 300 mm Hg) had met the acute lung injury standard, while which in VVT25 group was above 300 mmHg. Lung wet/dry ratio, BALF protein concentration, total nucleated cell and neutrophilic leukocyte were elevated in both VT25 and VT40 groups, of which 4 hours VT40 group was the highest. Conclusion Using 4 hours ventilation at a tidal volume of 40 mL/kg can successfully establish the rabbit model of ventilator-induced lung injury.