Objective To evaluate the effect of exogenous pulmonary surfactant(PS) replacement therapy for infants who suffered pulmonary injury after cardiopulmonary bypass. Methods Seven infants (age 0.49±0 82 year, weight 4.87±2.18kg) who depended on respiratory mechanical support with clinical and radiological evidence of pulmonary surfactant sufficiency were enrolled in the study. Oxygen index(OI), artery oxygen saturation(SaO 2) and artery bicarbonate pressure(PaCO 2) were measured at 4, 6, 12, 24, 48, and 72 h after the first application of PS(100mg/kg). At the meantime, maximum spontaneous respiratory tidal volume, chest X ray changes and ventilator time were recorded. Results Compared to the baseline values, OI and SaO 2 increased significantly 4 h after PS therapy, with a maximal increase slope (34.7%, 6.6%) after 24 h. While PaCO 2 decreased significantly 4 h after PS therapy, with a lowest decrease slope (22.8%) after 6 h ( P lt;0.05, 0.01). Spontaneous tidal volume and chest X ray si...更多gn were improved in all infants. The success rate of extubation was 85 7%. Conclusion Exogenous PS replacement therapy could improve pulmonary function for postoperative infants, and highly decrease the ventilator time.
ObjectiveTo investigate the expression of C/EBP homologous protein (CHOP) in lung tissue of chronic intermittent hypoxia rats, and explore the intervention effect of edaravone and its possible mechanism.MethodsA total of 120 adult male Wistar rats were randomly divided into three groups: a normal control group (UC group), a chronic intermittent hypoxia group (CIH group), an edaravone intervention group (NE group), and a normal saline group (NS group). The above four groups were also randomly divided into five time subgroups of 3 days, 7 days, 14 days, 21 days and 28 days, respectively, with 6 rats in each time subgroup. The histopathological changes of lung tissue were observed by hematoxylin-eosin (HE) staining and the expression of CHOP in lung tissue was detected by immunohistochemical method.ResultsHE staining results showed that there was no obvious pathological change in UC group. The epithelial cells of lung tissue in CIH group showed edema, hyperemia, widening of alveolar septum and inflammatory cell infiltration. The pathological injury was more serious with the prolongation of intermittent hypoxia time. There were also pathological changes in NE group, but the degree of lung tissue injury was significantly lower than that in CIH group. The results of immunohistochemistry showed that the expression of CHOP in CIH group was significantly higher than that in UC group. The expression of CHOP in NE group was higher than that in UC group, but it was still significantly lower than that in CIH group.ConclusionsThe expression of CHOP protein in lung tissue of chronic intermittent hypoxic rats is enhanced and the high expression of CHOP protein plays a certain role in the lung injury of chronic intermittent hypoxia rats complicated with lung injury. Edaravone may protect lung tissue from chronic intermittent hypoxia by inhibiting the expression of CHOP.
ObjectiveTo explore the effects of inhibition of paxillin phosphorylation on ventilation associated lung injury. MethodsSixty healthy male SD rats were randomly divided into four groups, namely a control group, a protective ventilation group, a high tidal volume ventilation group, and an inhibitor group. The rats in the control group received only tracheotomy and breathe naturally. The rats in the protective ventilation group received protective ventilation for 2 hours. The rats in the high tidal volume ventilation group and the inhibitor group received high tidal volume ventilation for 2 hours. The rats in the inhibitor group additionally received intraperitoneal injection of tyrosine protein kinase inhibitor PP2 before ventilation. All rats were sacrificed and the specimens of lung tissue were collected. The pathological changes of lungs were observed under light microscope and estimated by the diffuse alveolar damage (DAD) score system. The activity of myeloperoxidase (MPO) and the lungs wet/dry (W/D) weight ratio were measured. The expression of tumor necrosis factor-α(TNF-α) in BALF was detected by ELISA. Evans blue (EB) method was used to detect the pulmonary vascular permeability. The expression levels of phosphorylated paxillin (p-paxillin) and paxillin in lung tissue were measured by Western blot. Apoptosis in situ was detected by TUNEL. ResultsThere were significant differences in the W/D ratio, the EB extravasation, DAD score, the MPO activity and the TNF-αexpression in BALF between the high tidal volume ventilation group and the inhibitor group (P < 0.05). The apoptosis rate of each group was sorted from high to low as the high tidal volume ventilation group, the inhibitor group, the protective ventilation group, and the control group. The expression level of p-paxillin was the highest in the high tidal volume ventilation group which was significantly different from other groups (all P < 0.05). There was no significant difference in the expression of paxillin in the protective ventilation group, the high tidal volume ventilation group and the inhibitor group (P > 0.05). ConclusionInhibition of paxillin phosphorylation can significantly alleviate mechanical ventilation associated lung injury.
Objective To investigate the protective effects of endotoxin pretreatment on lung injury of rats with endotoxemia. Methods The rat model of acute endotoxemia was established by injecting lipopolysaccharide (LPS) intraperitoneally. Seventy-two male Wistar rats were randomly divided into three groups, ie. a saline control group (N, n=24) , a LPS-treated group (L, n=24) , and a LPS pretreated group ( P, n=24) . Each group was divided into 2 h, 4 h, 6 h, and 12 h subgroups. The rats in group P were firstly administered with introperitoneal injection of 0.25 mg/kg LPS. After 24 hours, they were subjected to the injection of 0.5 mg/kg LPS. The rats in group N and L received injection of equivalent amount of saline. After 72 hours, the rats in group L and P were challenged with intravenous injection of 10 mg/kg LPS, otherwise saline in group N. Six rats were killed at 2, 4, 6 and 12 hours respectively after injection of LPS in group L and P. The lungs were removed for detecting intercellular adhesion molecule-1 ( ICAM-1) , superoxide dismutase ( SOD) , and malondialdehyde (MDA) . Meanwhile the level of tumor necrosis factoralpha ( TNF-α) in serum was measured, and the pathological changes of lung were also examined. Results The contents of ICAM-1, MDA and TNF-α in the LPS-treated 4 h group were 75.07 ±0. 53, ( 3.93 ± 0.42) μmol/g, and (478.62 ±45.58) pg/mL respectively, significantly higher than those in the saline control group. The endotoxin pretreatment reduced the above indexes to 42.40 ±0.44, ( 2.89 ±0.49) μmol / g and ( 376.76 ±43.67) pg/mL respectively (Plt;0.05) . The content of SOD in the LPS-treated 4 h group was ( 6.26 ±0.31) U/mg, significantly lower than that in the saline control group. The endotoxin pretreatment increased SOD to ( 8.79 ±0.35) U/mg. Conclusion Endotoxin pretreatment can suppress the progress of lung injury in rats with endotoxemia and protect the lung tissue by down-regulating the inflammatory response and oxygen free radical production.
Objective To explore the migration and differentiation of bone marrow mesenchymal stem cells（MSCs） in lung . Methods MSCs were harvested from a male Wister rat. Sixty female Wister rats were randomly divided into four groups. The pulmonary fibrosis model was established by intratracheal instillation of bleomycin in group A-D. Immediately and 7 days after bleomycin administration respectively，the rats in group B and C received infusion with 5-bromodeoxynridine （BrdU） labeled MSCs via tail vein. And the rats in group D were infused MSCs without BrdU labeling serving as a negative control. The sry gene of Y chromosome was detected by polymerase chain reaction （PCR）. Double immunofluorescence staining was used to detected BrdU and surfactant associated protein-C （SP-C） expression in lung tissue，fresh bone marrow，and the 5th generation MSCs. Reverse transcriptipon-PCR was used to detect the expressions of SP-C mRNA and AQP-5 mRNA. Results The sry gene was detected in bleomycin induced lung injury tissues of the rats after MSCs infusion immediately and on the 7th day The MSCs in lung tissue could transformed into cells with ACEⅡ morphological features and molecular phenotype. The transformation rate was higher in the rats received MSCs infusion immediately than the rats received on 7th day. The 5th generation MSCs and fresh bone marrow expressed SP-C mRNA，without AQP-5 mRNA and SP-C expression. Conclusions Exogenous MSCs can be transplanted into injured lung tissues and transform into AECⅡ，especially in early stage of lung injury. The differentiation potential of MSCs can be activated in injury micro-environment.
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.
ObjectiveTo investigate the effects of esophageal cooling (EC) on lung injury and systemic inflammatory response after cardiopulmonary resuscitation in swine.MethodsThirty-two domestic male white pigs were randomly divided into sham group (S group, n=5), normothermia group (NT group, n=9), surface cooling group (SC group, n=9), and EC group (n=9). The animals in the S group only experienced the animal preparation. The animal model was established by 8 min of ventricular fibrillation and then 5 min of cardiopulmonary resuscitation in the other three groups. A normal temperature of (38.0±0.5)℃ was maintained by surface blanket throughout the experiment in the S and NT groups. At 5 min after resuscitation, therapeutic hypothermia was implemented via surface blanket or EC catheter to reach a target temperature of 33℃, and then maintained until 24 h post resuscitation, and followed by a rewarming rate of 1℃/h for 5 h in the SC and EC groups. At 1, 6, 12, 24 and 30 h after resuscitation, the values of extra-vascular lung water index (ELWI) and pulmonary vascular permeability index (PVPI) were measured, and meanwhile arterial blood samples were collected to measure the values of oxygenation index (OI) and venous blood samples were collected to measure the serum levels of tumor necrosis factor-α (TNF-α) and inerleukin-6 (IL-6). At 30 h after resuscitation, the animals were euthanized, and then the lung tissue contents of TNF-α, IL-6 and malondialdehyde, and the activities of superoxide dismutase (SOD) were detected.ResultsAfter resuscitation, the induction of hypothermia was significantly faster in the EC group than that in the SC group (2.8 vs. 1.5℃/h, P<0.05), and then its maintenance and rewarming were equally achieved in the two groups. The values of ELWI and PVPI significantly decreased and the values of OI significantly increased from 6 h after resuscitation in the EC group and from 12 h after resuscitation in the SC group compared with the NT group (all P<0.05). Additionally, the values of ELWI and PVPI were significantly lower and the values of OI were significantly higher from 12 h after resuscitation in the EC group than those in the SC group [ELWI: (13.4±3.1) vs. (16.8±2.7) mL/kg at 12 h, (12.4±3.0) vs. (16.0±3.6) mL/kg at 24 h, (11.1±2.4) vs. (13.9±1.9) mL/kg at 30 h; PVPI: 3.7±0.9 vs. 5.0±1.1 at 12 h, 3.4±0.8 vs. 4.6±1.0 at 24 h, 3.1±0.7 vs. 4.2±0.7 at 30 h; OI: (470±41) vs. (417±42) mm Hg (1 mm Hg=0.133 kPa) at 12 h, (462±39) vs. (407±36) mm Hg at 24 h, (438±60) vs. (380±33) mm Hg at 30 h; all P<0.05]. The serum levels of TNF-α and IL-6 significantly decreased from 6 h after resuscitation in the SC and EC groups compared with the NT group (all P<0.05). Additionally, the serum levels of IL-6 from 6 h after resuscitation and the serum levels of TNF-α from 12 h after resuscitation were significantly lower in the EC group than those in the SC group [IL-6: (299±23) vs. (329±30) pg/mL at 6 h, (336±35) vs. (375±30) pg/mL at 12 h, (297±29) vs. (339±36) pg/mL at 24 h, (255±20) vs. (297±33) pg/mL at 30 h; TNF-α: (519±46) vs. (572±49) pg/mL at 12 h, (477±77) vs. (570±64) pg/mL at 24 h, (436±49) vs. (509±51) pg/mL at 30 h; all P<0.05]. The contents of TNF-α, IL-6, and malondialdehyde significantly decreased and the activities of SOD significantly increased in the SC and EC groups compared with the NT group (all P<0.05). Additionally, lung inflammation and oxidative stress were further significantly alleviated in the EC group compared with the SC group [TNF-α: (557±155) vs. (782±154) pg/mg prot; IL-6: (616±134) vs. (868±143) pg/mg prot; malondialdehyde: (4.95±1.53) vs. (7.53±1.77) nmol/mg prot; SOD: (3.18±0.74) vs. (2.14±1.00) U/mg prot; all P<0.05].ConclusionTherapeutic hypothermia could be rapidly induced by EC after resuscitation, and further significantly alleviated post-resuscitation lung injury and systemic inflammatory response compared with conventional surface cooling.
ObjectiveTo investigate the effects of interleukin (IL)-26 on the late phase of lipopolysaccharides (LPS)-induced lung inflammation in mouse model.MethodsThirty-two mice were equally and randomly divided into four groups: blank control group, IL-26 control group, LPS model group, and IL-26 intervention group. The blank control group was given intranasal administration of phosphate buffered solution (PBS, 40 μl) and PBS (40 μl) 10 minutes apart. The IL-26 control group was given recombinant human interleukin-26 (rhIL-26; 50 μg/kg, dissolved in 40 μg PBS) and PBS successively. The LPS model group was given intranasal administration of PBS (40 μl) and LPS (10 mg/kg, dissolved in 40 μl PBS) at 10 minutes interval. The IL-26 intervention group was given intranasal administration of rhIL-26 and LPS at 10 minutes interval. Seventy-two hours later after treatment, bronchoalveolar lavage fluid (BALF) cell count, cytokine assay and pathological staining of lung tissue were performed in each group. The gene expression of inflammatory pathway in lung tissue was detected by RT-PCR. One-way ANOVA was used for comparison between groups. ResultsCompared with the blank control group, the expression of tumor necrosis factor-α and activating transcription factor 3 in IL-26 control group increased significantly (all P < 0.05). The number of peripheral blood mononuclear cells, total BALF cells, lymphocytes and neutrophils, and the content of macrophage inflammatory protein-1a in BALF were significantly increased in IL-26 intervention group comparing with LPS model group (all P < 0.05). IL-26 intervention group had more inflammatory subsidence in interstitial, perivascular, peribronchial and mean values than LPS model group (all P < 0.05). The expressions of Toll-like receptor 4, Toll-like receptor 2 and interferon γ induced protein 10 in IL-26 intervention group were significantly higher than those in LPS model group (all P < 0.05).ConclusionIL-26 can significantly alleviate the late inflammatory reaction of lung tissue in LPS-induced mouse inflammation model.