Objective To study the effects of edaravone on the lung injury of severe acute pancreatitis （SAP） in rats. Methods Thirty-six SD rats were randomly divided into three groups: normal control group, model group and edaravone group, and SAP was induced by intraductal administration of 5% sodium taurocholate. Edaravone was given in edaravone group, while normal saline was given in normal control group and model group. After operation 6 h rats were executed, and dry/wet weight (D/W) ratio of lung was counted, and malondialdehyde (MDA) content, superoxide dismutase (SOD) activity in serum and lung were detected, respectively. In addition, the levels of tumor necrosis factor-α (TNF-α), interleukin-1, -6 (IL-1, -6) of serum were detected.Results The MDA contentof serum and lung and the levels of TNF-α, IL-1, IL-6 in model group were markedly higher than those in normal control group and edaravone group, but D/W ratio of lung, SOD activity of serum and lung were significantly lower (Plt;0.05). Conclusion Edaravone can alleviate lung injury of rats caused by SAP.
Objective To investgate the expression of p38 mitogen-activated protein kinase （p38MAPK） in lung tissue of rats with severe acute pancreatitis （SAP）， and to explore the relationship between p38MAPK and pulmonary capillary barrier injury. Methods Forty male and healthy Sprague-Dawley （SD） rats were randomly （random number method） divided into sham operation （SO） group and SAP group， then rats of SAP group were sub-divided into 3， 6， 12， and 24 h group， each group enrolled 8 rats， respectively. SAP model rats were established by injecting 5% sodium taurocholate solution retrograde into the biliopancreatic duct. ELISA method was used to test the serum tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）， and pathological changes in lung and pancreas tissues were observed by HE staining. Immunohischemistry method was used to detect phosphorylated p38 （p-p38） protein and aquaporin 1 （AQP1） protein of lung tissues. The expression level of AQP1 mRNA was measured by quantitative real-time PCR. Results Hyperemia， edema， and inflammatory cell infiltration were observed in lung tissues， abundance of necrosis， part gland structure fuzzy or even disappear were observed in pancreas tissues of all 4 time point groups. Compared with SO group， levels of serum TNF-α and IL-1β were significantly higher in 4 time point groups （P＜0.05）. Lower expression level of p-p38 protein was detected in lung tissues of SO group， while in the early stage of SAP （SAP 3 h group）， the expression level of p-p38 protein significantly increased， which peaked in 6 h group and was still higher than SO group in 24 h group （P＜0.05）. Compared with SO group， the expression levels of AQP1 mRNA and protein were significantly lower in all 4 time point groups （P＜0.05）， which had negative correlation with the levels of serum TNF-α，IL-1β， and the expression level of p-p38 protein （r=-0.87， P＜0.05；r=-0.88， P＜0.05；r=-0.78， P＜0.05）. Conclusion The decrease of AQP1 protein in lung tissue is one of the vital causes for pulmonary capillary barrier injury in SAP， which probably works by the activation of p38MAPK and the excessive release of inflammatory cytokines.
ObjectiveTo discuss the risk factors of acute respiratory distress syndrome (ARDS) in patients with severe pneumonia.MethodsData of 80 patients with severe pneumonia admitted in our ICU were analyzed retrospectively, and they were divided into two groups according to development of ARDS, which was defined according to the Berlin new definition. The age, gender, weight, Acute Physiology and Chronic Health EvaluationⅡscore, lactate, PSI score and LIPS score, etc. were collected. Statistical significance results were evaluated by multivariate logistic regression analysis after univariate analysis. Receiver operating characteristic (ROC) curve was plotted to analyze the predictive value of the parameter for ARDS after severe pneumonia.ResultsForty patients with severe pneumonia progressed to ARDS, there were 4 moderate cases and 36 severe cases according to diagnostic criteria. Univariate analysis showed that procalcitonin (t=4.08, P<0.001), PSI score (t=10.67, P<0.001), LIPS score (t=5.14, P<0.001), shock (χ2=11.11, P<0.001), albumin level (t=3.34, P=0.001) were related to ARDS. Multivariate logistic regression analysis showed that LIPS ［odds ratio (OR) 0.226, 95%CI=4.62-5.53, P=0.013］ and PSI (OR=0.854, 95%CI=132.2-145.5, P=0.014) were independent risk factors for ARDS. The predictive value of LIPS and PSI in ARDS occurrence was significant. The area under ROC curve (AUC) of LIPS was 0.901, the cut-off value was 7.2, when LIPS ≥7.2, the sensitivity and specificity were both 85.0%. AUC of PSI was 0.947, the cut-off value was 150.5, when PSI score ≥150.5, the sensitivity and specificity were 87.5% and 90.0% respectively.ConclusionsPSI and LIPS are independent risk factors of ARDS in patients with severe pneumonia, which may be references for guiding clinicians to make an early diagnosis and treatment plan.
Objective To observe the effects of melatonin on lung injury and NDRG2 ( N-myc downstream-regulated gene 2) expression after intestinal ischemia-reperfusion ( I/R) .Methods 40 healthy SD rats were randomly assigned to a sham group, an I/R group, a high-dose melatonin group ( 10 mg/kg) , and a low-dose melatonin group ( l mg/kg) . The model of lung injury was established by superior mesenteric artery clamping/unclamping. 30 minutes before clamping, melatonin was administered intraperitoneally to the rats in two melatonin groups, and normal saline in same volume was administered to the rats in the I/R group and the shamgroup. Then superior mesenteric arteries of the rats in the I/R group and two melatonin groups were clamped for 60 minutes. 45 minutes after unclamping, right lung tissues were sampled for pathological examination and wet/dry ( W/D) ratio measurement. The rats in the sham group underwent sham operation without clamping. The expression of NDRG2 protein in the lung tissue was detected by immunohistochemistry and Western-blot. Results Compared with the sham group, hemorrhage and inflammation of lung tissues were observed. The W/D was obviously increased and the NDRG2 expression was significantly decreased in the I/R group. Compared with the I/R group, mild hemorrhage and inflammation changes of lung tissues were observed and the W/D was decreased while the NDRG2 protein expression was increased significantly in two melatonin groups. There was no significant difference between two melatonin groups. Conclusion Melatonin may relieve lung injury after intestinal ischemia-reperfusion through up-regulating NDRG2 expression.
Objective To determine if mesenchymal stem cells ( MSCs) could be reconstructed as a vehicle for angiopoietin-1 ( Ang1) gene therapy in lung injury. Methods MSCs were obtained from adult male inbred mice and cultured to passage four. The cells were identified by fluorescence-activated cell sorting ( FACS) analysis and cell differentiation detection. Lentiviral vectors contained GFP and Ang1 gene were conducted in 293T cells through three plasmids co-transfection method. Then MSCs were transduced with Ang1 gene efficiently through lentiviral vectors. The mRNA expression of Ang1 in MSCs was detected by RT-PCR before and after transfection. Also fluorescence from MSCs was detected by fluorescence microscope every day after transfection. Two hours after LPS inhalation, mice were infused via jugular veinwith normal saline ( NS group) , lentiviral vector carrying Ang1 ( Ang1 group) , lentiviral vector carrying GFP ( MSCs group) , and lentiviral vector carrying Ang1 /GFP ( MSCs-Ang1 group) , respectively. Kaplan-Meier survival analysis was performed to compare the effects of MSCs-Ang1 on survival. And ectogenic MSCs origined lung cells were investigated in receipt mice. Results After passaged and purification,MSCs were confirmed to have the potential of differentiation. The lentiviral vectors carrying Ang1 and GFP were also identified. After transfection, the mRNA expression of Ang1 in MSCs was enhanced. Through the fluorescence microscope,MSCs get the most green fluorescence expression five days after the transfection when MOI was 20. Kaplan-Meier survival analysis showed that MSCs-Ang1 infusion had improved survival rates of lung injury rats compared with the control, but it did not reach statistical significance ( P = 0. 066) . Cells expressing GFP in lung tissues can be observed after MSCs were transplanted in vivo. Conclusions MSCs expressing Ang1 high can be constructed through lentiviral vector transfer, and MSCs-origined cells can be detected in receipt lungs after transplantation. So MSCs may serve as a vehicle for gene therapy in lung injury.
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.
Objective To study the effects of two different tidal volume mechanical ventilation on lipopolysaccharide( LPS) -induced acute lung injury( ALI) , and explore the effects of glutamine on ALI.Methods Thirty male Sprague-Dawley rats were randomly divided into three groups. After anesthesia and tracheotomy were performed, the rats were challenged with intratracheal LPS ( 5mg/kg) and received ventilation for 4 hours with small animal ventilator. Group A received conventional tidal volume, while groupB received large tidal volume. Group C received large tidal volume as well, with glutamine injected intravenously 1 hour before ventilation. Arterial blood gases were measured every one hour. 4 hours later, the rats were killed by carotid artery bleeding. The total lung wetweightwas measured and lung coefficient ( total lung wet weight /body weight ×100) was counted. WBCs and neutrophils in BALF were counted. Protein concentration, TNF-α, IL-6, and cytokine-induced neutrophil chemoattractant-1 ( CINC-1) levels in BALF,myeloperoxidase ( MPO) , and superoxide dismutase ( SOD) levels in the lung were assayed respectively.Results PaO2 and SOD levels decreased more significantly in group B than those of group A. The lung coefficient, WBCs, neutrophils, protein, TNF-α, IL-6, and CINC-1 levels in BALF, MPO levels in lung increased more significantly in group B than those of group A. PaO2 and SOD levels were significantly higher in group C than those of group B. The lung coefficient, WBCs, neutrophils, protein, TNF-α, IL-6, and CINC-1 levels in BALF,MPO levels in lung were significantly lower in group C than those of group B. Conclusion Large tidal volume mechanical ventilation aggravates LPS-induced ALI, and glutamine has obviouslyprotective effects.
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.
ObjectiveTo summarize the changes and interaction of the cytokine in severe acute pancreatitis associated lung injury. MethodsThe published literatures at domestic and aboard in recent years about severe acute pancreatitis associated lung injury were collected and reviewed. ResultsThe cytokines had a chain effect, and influenced each other when severe acute pancreatitis with lung injury attacked. ConclusionsRelated cytokines play important roles in severe acute pancreatitis associated lung injury. Researching the related cytokines will contribute to the diagnosis and treatment for severe acute pancreatitis with lung injury.