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.
The contents of lipid peroxides(LPO)and vitamin E(V.E)and some functional index and histologic changes in the lungs from the the rabbit models of acute cholangitis of severe type(ACST)were measured dynamically.The results revealed that the V.E content decreased strikingly from 6 hours and the LPO level increased progressivelg from 12 hours in the lungs.Simultanuosly,the congestion and neutrophil infiltreation in the lung mesenchyme,and the endothelial cell damage and thrombosis in the lung blood capillaries had been observed.These suggest that acute lung injury induced by ACST is referable to the lipid peroxidation damage to the lung blood capillaries which is due to increased LPO and decreased antioxidants including V.E.
Objective To study the protective effects and mechanism of intermittent ventilation on lung injury during cardiopulmonary bypass(CPB). Methods Twenty-four patients with rheumatic heart disease (RHD) were divided into two groups with random number table: treatment group (n=13),given intermittent ventilation once every 5 minutes during CPB; control group (n=11),no ventilation during CPB. Blood samples were obtained preoperatively. A bronchoalveolar lavage was performed at 2 hours after CPB. The numbers of granulocytes, total protein (TP) and tumor necrosis factor-alpha(TNF-α) content in the bronchoalveolar lavage fluids(BALF) were measured, and lung oxygenate index (OI) were measured preoperatively and 1 hour, 4 hours after CPB termination,respectively. Results The numbers of granulocytes, TP and TNF-α content of treatment group in the BALF were significantly lower than those of the control group (Plt;0.01, P=0.02,0.02),and the lung OI of treatment group at 1 hour and 4 hours after CPB termination was also significantly lower than that of the control group(Plt;0.05); a significant increase of lung OI occurred in both groups at 1 hour and 4 hours after CPB when compared with the same group at baseline before CPB(Plt;0.05). Conclusion Intermittent ventilation has the protective effects on lung injury during CPB by decreasing granulocytes adhesion and alleviating lung inflammatory reaction and endothelial cells injury.
【Abstract】Objective To investigate the role of interleukin-10（IL-10） and interleukin-18 （IL-18） in the pathogenesis of acute lung injury in experimental severe acute pancreatitis.Methods Forty-eight SD rats were divided into control group and SAP group by the random data table. The model of experimental severe acute pancreatitis was established by injection of 3.5% sodium taurocholate into the bili-pancreatic duct. Lung wet weight index, ascities and level of serum amylase, IL-10 and IL-18 were quantitatively measured in different time. Intrapulmonary expressions of IL-10 mRNA and IL-18 mRNA were detected by semiquantitative RTPCR. The histopathology of pancreas and lung were observed under the light microscope.Results Lung wet weight index, ascities, level of serum amylase, IL-10 and IL-18, intrapulmonary expressions of IL-10 mRNA and IL-18 mRNA were significantly increased in SAP group (P＜0.01). The level of serum IL-18 and intrapulmonary expression of IL-18mRNA are positively correlated with lung wet weight index （r=0.68,P＜0.01; r=0.72,P＜0.01） and lung injury score （r=0.74,P＜0.01; r=0.79,P＜0.01) respectively, whereas the level of serum IL-10 and intrapulmonary expression of IL-10 mRNA are negatively correlated with lung wet weight index（r=-0.62,P＜0.01; r=-0.69,P＜0.01） and lung injury score（r=-0.66,P＜0.01; r=-0.60,P＜0.01）. Conclusion IL-18 may play a key role in the pathogenesis of acute lung injury in experimental severe acute pancreatitis, and IL-10 exerts the protection role in this process.
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 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.
Objective To determine the risk factors for acute lung injury（ALI） early after orthotopic liver transplantation.Methods The perioperative clinical data of all 275 patients who had undergone orthotopic liver transplantation were analysed retrospectively.Several statistically significant risk factors were screened out with univarite analysis，then independent risk factors were determined with multivariate stepwise logistic regression analysis.Results Of the all 275 patients，the morbidity of ALI was 9.8% with a mortality of 22.2%.Univariate analysis showed that the occurrence of ALI was associated with preoperative infection，severe hepatitis，renal dysfunction，massive blood transfusion in operation，long non-hepatic period and long cold ischemic time.Multivarite stepwise logistic regression analysis revealed that the independent risk factors for ALI were massive blood transfusion in operation（OR=12.12，95%CI 0.958-25.364），longer non-hepatic period（OR=1.23，95%CI 1.034-1.410） and longer cold ischemic time（OR=22.35，95%CI 1.266-43.421）.Conclusion Massive blood transfusion in operation，long non-hepatic period and long cold ischemic time were independent risk factors for ALI early after orthotopic liver transplantation.
Objective Observing the expressions of inducible nitric oxide synthase （iNOS） and endothelial nitric oxide synthase （eNOS） mRNA in lung tissues of rats with acute necrotizing pancreatitis （ANP） to explore the role of NOS in ANP associated-lung injury. Methods Forty Wistar rats were assigned into ANP group (n=30) and sham-operation group (SO group, n=10). ANP model was induced by retrograde injection of 5% sodium taurocholate into the bili-pancreatic duct. Pathological changes of the lung tissue were observed under light microscope at 3 h, 6 h and 12 h after the ANP-model operation, and the expressions of iNOS mRNA and eNOS mRNA in lung tissue were assayed by RT-PCR. Results Different degrees of pathological changes of the lung tissue, such as hyperemia, edema, inflammatory cells infiltration, hemorrhage and necrosis, were found in the ANP group. The pathologic injury scores of lung tissue in ANP group were higher than that in SO group (Plt;0.05), and gradually increased with the duration extension of ANP (Plt;0.05). Compared with the SO group, the expressions of iNOS and eNOS mRNA in ANP group were all higher at 3 h, 6 h, and 12 h (Plt;0.05). Conclusions The overexpressions of iNOS and eNOS mRNA may play important roles in lung injury of ANP. This provides us a theory basis that lung injury of ANP could be relieved by inhibiting the expressions of iNOS and eNOS mRNA.
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.