Objective To investigate the effects of different levels of intra-abdominal pressure ( IAP) on respiration and hemodynamics in a porcine model of acute lung injury( ALI) .Methods A total of 8 domestic swine received mechanical ventilation. Following baseline observations, oleic acid 0. 1mL/kg in 20mL of normal saline was infused via internal jugular vein. Using a nitrogen gas pneumoperitongum, the IAP increased from0 to 15 and 25mmHg, and the groups were named IAP0 , IAP15 and IAP25 , respectively. During the experimental period, hemodynamic parameters including heart rate ( HR) , cardiac output ( CO) , mean arterial pressure( MAP) , central venous pressure( CVP) , intrathoracic blood volume index( ITBVI) and so on were obtained by using thermodilution technique of pulse induced continuous cardiac output( PiCCO) . The esophageal pressure( Pes) was dynamicly monitored by the esophageal catheter. Results Pes and peak airway pressure( Ppeak) increased and static lung compliance( Cstat) decreased significantly in IAP15 and IAP25 groups compared with IAP0 group( all P lt;0. 01) . Transpulmonary pressure( Ptp) showed a downward trend( P gt;0. 05) . PO2 and oxygenation index showed a downward trend while PCO2 showed a upward trend ( P gt;0. 05) . HR and CVP increased significantly, cardiac index( CI) and ITBV index decreased significantly ( all P lt;0. 05) ,MAP didn′t change significantly( P gt;0. 05) . The changes in Pes were negatively correlated with the changes in CI( r = - 0. 648, P = 0. 01) . Conclusion In the porcine model of ALI, Pes increases because of a rise in IAP which decreased pulmonary compliance and CI.
Objective To detect the expression of single immunoglobin IL-1 receptor related protein ( SIGIRR) in normal human lung tissues, and study its changes in alveolar epithelial cell acutely injured by lipopolysaccharide ( LPS) . Methods Twenty samples of human normal lung tissue were collected during the lobectomies. The expression of SIGIRR was detected by immunohistochemistry, western blot and RT-PCR. The human type II alveolar epithelial cell acute injury model was established by stimulating A549 cells with LPS of a final concentration of 10 μg/mL. The cells were collected at 0, 3, 6, 12, and 24 hours after the stimulation. The changes of SIGIRR expression at the same time points were observed by western blot. The expression vector containing full-length SIGIRR cDNA was transfected transiently into A549 cells to induce SIGIRR overexpression. MTT assay was performed to measure the injury of A549 cells caused by LPS. Results The immunohistochemistry, western blot and RT-PCR showed that there was a high expression of SIGIRR in normal human lung tissues. The expression of SIGIRR was located in alveolar epithelial cells by immunohistochemistry. The expression of SIGIRR at 3, 6, and 12 hours was down-regulated after LPSstimulation and raised again at 24 hours to the baseline. MTT assay showed that SIGIRR overexpression substantially reduced the growth inhibition ratio of A549 cells after LPS stimulation. Conclusions Expression of SIGIRR in normal human lung tissues was confirmed by different detection methods. SIGIRR alleviates the injury of alveolar epithelial cells caused by LPS, implying SIGIRR might be involved in the regulationof acute lung injury mediated by LPS.
Objective To evaluate the efficiency and associated factors of noninvasive positive pressure ventilation( NPPV) in the treatment of acute lung injury( ALI) and acute respiratory distress syndrome( ARDS) .Methods Twenty-eight patients who fulfilled the criteria for ALI/ARDS were enrolled in the study. The patients were randomized to receive either noninvasive positive pressure ventilation( NPPV group) or oxygen therapy through a Venturi mask( control group) . All patients were closely observed and evaluated during observation period in order to determine if the patients meet the preset intubation criteria and the associated risk factors. Results The success rate in avoiding intubation in the NPPV group was 66. 7%( 10/15) , which was significantly lower than that in the control group ( 33. 3% vs. 86. 4% , P = 0. 009) . However, there was no significant difference in the mortality between two groups( 7. 7% vs.27. 3% , P =0. 300) . The incidence rates of pulmonary bacteria infection and multiple organ damage were significantly lower in the NPPV success subgroup as compared with the NPPV failure group( 2 /10 vs. 4/5, P =0. 01;1 /10 vs. 3/5, P = 0. 03) . Correlation analysis showed that failure of NPPV was significantly associated with pulmonary bacterial infection and multiple organ damage( r=0. 58, P lt;0. 05; r =0. 53, P lt;0. 05) . Logistic stepwise regression analysis showed that pulmonary bacterial infection was an independent risk factor associated with failure of NPPV( r2 =0. 33, P =0. 024) . In the success subgroup, respiratory rate significantly decreased( 29 ±4 breaths /min vs. 33 ±5 breaths /min, P lt; 0. 05) and PaO2 /FiO2 significantly increased ( 191 ±63 mmHg vs. 147 ±55 mmHg, P lt;0. 05) at the time of 24 hours after NPPV treatment as compared with baseline. There were no significant change after NPPV treatment in heart rate, APACHEⅡ score, pH and PaCO2 ( all P gt;0. 05) . On the other hand in the failure subgroup, after 24 hours NPPV treatment, respiratory rate significantly increased( 40 ±3 breaths /min vs. 33 ±3 breaths /min, P lt;0. 05) and PaO2 /FiO2 showed a tendency to decline( 98 ±16 mmHg vs. 123 ±34 mmHg, P gt; 0. 05) . Conclusions In selected patients, NPPV is an effective and safe intervention for ALI/ARDS with improvement of pulmonary oxygenation and decrease of intubation rate. The results of current study support the use of NPPV in ALI/ARDS as the firstline choice of early intervention with mechanical ventilation.
Objective To observe the effects of nitric oxide ( NO) inhalation on lung inflammation of acute lung injury ( ALI) in rats. Methods Twenty-four SD rats were randomly divided into four groups, ie. a normal control group, an ALI group, a 20 ppm NO inhalation group, and a 100 ppm NO inhalation group. ALI model was established by LPS instillation intratracheally and the control group was instilled with normal saline. Then they were ventilated with normal air or NO at different levels, and sacrificed 6 hours later. Pathological changes were evaluated by HE staining. The expression of TLR4 in lung tissues was detected by immunohistochemistry. IL-6 level in lung homogenate was measured by ELISA. Results In the ALI group, the inflammation in bronchus and bronchioles was more apparently, and the expressions of TLR4and IL-6 were elevated significantly compared with the control group. 20 ppm NO inhalation significantly decreased the expression of TLR4 and IL-6, and alleviated the inflammation of ALI. However, 100 ppm NO inhalation did not change TLR4 expression and lung inflammation significantly, and increased IL-6 level.Conclusions Inhalation low level of NO( 20 ppm) can alleviate lung inflammation possibly by reducing theexpression of TLR4 and IL-6.
Objective To investigate the influence of chronic alcohol ingestion on the severity of acute lung injury (ALI) induced by oleic acid and lipopolysaccharide (LPS).Methods Thirty-two SD rats were randomly administrated with alcohol or water for 6 weeks，then instilled with oleic acid and LPS to induce ALI or with normal saline as control.Thus the rats were randomly divided into two injury groups [ethanol group and water group] and two control groups [ethanol group and water group] (n=8 in each group). PaO2,Wet to dry lung weight ratio (W/D)，levels of γ-glutamylcysteinylglycine (GSH) and malonaldehyde (MDA) in the lung tissue were measured.Results Compared to corresponding control groups，the PaO2 and GSH significantly decreased，and the lung W/D and MDA level were significantly increased in the injury groups (all Plt;0.05).In the injury groups，the changes of above parameters were more significant in the alcohol group than thoe in the water group (all Plt;0.05)，except the lung W/D with no significant difference.Conclusion Chronic ethanol ingestion was relevalent to oxidation/ antioxidation imbalance and more severe lung injury in rats with severe septic after trauma,which suggests that chronic alcohol abuse could increase the severity of acute lung injury.
Objective To investigate the transduction pathway of TREM-1 during endotoxininduced acute lung injury ( ALI) in mice through the specific activating or blocking TREM-1.Methods 40 mice were randomly divided into a saline control group, an ALI group, an antibody group, and a LP17 group ( 3.5 mg/kg) . All mice except the control group were intraperitoneally injected with lipopolysaccharide ( LPS) to establish mouse model of ALI. Two hours after LPS injection, anti-TREM-1mAb ( 250 μg/kg) was intraperitoneally injected in the antibody group to activation TREM-1, and synthetic peptide LP17 was injected via tail vein in the LP17 group to blocking TREM-1. After 6,12,24, 48 hours, 3 mice in each group were sacrificed for sampling. The expression of NF-κB in lung tissue was determined by immunohistochemistry. The levels of TNF-α, IL-10, TREM-1, and soluble TREM-1 ( sTREM-1) in lung tissue and serumwere measured by ELISA. Pathology changes of lung were observed under light microscope, and Smith’s score of pathology was compared. Results Administration of anti-TREM-1mAb after ALI modeling significantly increased the NF-κB expression in lung tissue at 48h, resulting in a large number of pro-inflammatory cytokines releasing in the lung tissue and serumand lung pathology Smith score increasing. Administration of LP17 after modeling significantly down-regulated the expressions of NF-κB and pro-inflammatory cytokines, while led to a slight increase of anti-inflammatory cytokines and a decline of lung pathology Smith’s score.Conclusion TREM-1 may involve in inflammatory response by promoting the generation of inflammatory factors via NF-κB pathway, thus lead to lung pathological changes in ALI.
Objective To review the basic research, the cl inical progress, and the mechanism of bone marrow mesenchymal stem cells (BMSCs) in acute lung injury (ALI). Methods The l iterature concerning the basic and cl inical researches of BMSCs in ALI was reviewed. Results BMSCs can take the initiative to “homing” the site of lung injury and take partici pate in repair by means of differentiation, meanwhile BMSCs could regulate and balance local and systematic inflammatory response and immune disorders in ALI. Currently, the mechanism of BMSCs on anti-inflammation and immune regulation in ALI is not clear. Conclusion BMSCs have comprehensive biological effect on ALI, providing a potential cl inical treatment and also laying the foundation for gene therapy and stem cell therapy of ALI in the future.
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.
Objective To observe the protective effects of ambroxol hydrochloride ( AMB) on rabbit model of acute lung injury ( ALI) induced by oleic acid and explore its mechanisms. Methods The ALI model of rabbit was induced by oleic acid. Twenty-four Japanese white rabbits were divided into three groups randomly, ie. a normal saline group ( NC group) , an ALI group and an ALI plus ambroxol injection group ( AMB group) . The pathological changes and apoptotic index ( AI) in lung tissue, Caspase-3 activity in lung tissue homogenate were observed 6 hours after the intervention. Serum activity of superoxide dismutase ( SOD) and serum levels of malonaldehyde ( MDA) , interleukin-1β( IL-1β) , and tumor necrosis factor-α ( TNF-α) were measured simutanously. Results The pathological injury of lung in the AMB group was milder than that in the ALI group. Both the AI in lung tissue and Caspase-3 activity in homogenate in the AMB group were lower than those in the ALI group significantly ( P lt;0. 01, P lt;0. 05 respectively) , butwere higher than those in the NC group( both P lt; 0. 01) . The activity of SOD in serum measured 6 hours after AMB intervention was higher while the serum levels of MDA, IL-1βand TNF-αin serum were lower ( P lt;0. 01) than those in the ALI group significantly ( all P lt;0. 01) . Conclusions Ambroxol hydrochloride has protective effects on oleic acid-induced acute lung injury. The mechanisms may be related to inhibition of oxidative stress and suppression of cytokines synthesis ( IL-1βand TNF-α) , the activity of the Caspase-3,and the apoptosis of lung tissue.
ObjectiveTo compare two different ways to establish mouse model with acute lung injury (ALI) via intratracheal instillation or intraperitoneal injection of lipopolysaccharide (LPS). MethodsBALB/c mice received intraperitoneal/intratracheal administration of LPS or sham operation. Wet/dry lung weight ratio, protein concentration in bronchoalveolar lavage fluid (BALF), and lung tissue histology were examined at 0, 1, 2, 6, 12, 18, 24, 48 h after LPS administration. Tumor necrosis factor-α (TNF-α) in BALF and serum was assayed with ELISA method. ResultsLPS treatment significantly increased wet/dry lung weight ratio, BALF protein concentration and TNF-α concentration in serum and BALF. Lung tissue was damaged after LPS challenge. The mice received LPS intraperitoneal injection got a more significant lung edema than those received LPS intratracheal instillation. Inversely, LPS intratracheal instillation induced more severed microstructure destruction. ConclusionsALI animal model by LPS intratracheal instillation or intraperitoneal injection induces inflammation and tissue damage in lung. However, the degree of tissue damage or self-healing induced by two methods is different. Therefore the decision of which way to establish ALI model will depend on the study purpose.