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 investigate whether p38 mitogen activated protein kinase (p38MAPK) inhibitor can reduce acute lung injury (ALI) caused by lipopolysaccharide (LPS) by regulating Th17/Treg balance. Methods Balb/c mice were randomly divided into a control group, an ALI group and an intervention group. The mice in the control group were injected with phosphate-buffered saline, the mice in the ALI group were intraperitoneally injected with 40 mg/kg LPS, and the mice in the intervention group were injected with SB203580 (0.5 mg/kg, 1 mg/kg, 2 mg/kg, 5 mg/kg) intraperitoneally 1 h prior to the intraperitoneal injection of LPS. All mice were killed on 12 h later respectively. Hematoxylin-eosinstin staining was used to observe the pathological changes of lung tissue, and cell classification, counting, and total protein levels in bronchoalveolar lavage fluid (BALF) were detected. Transcript expression of forkhead box p3 (Foxp3) and retinoic acid receptor-related orphan receptor-γt (RORγt) was detected by real-time polymerase chain reaction. Interleukin (IL)-6, IL-10, IL-17, IL-23 and transforming growth factor-β (TGF-β) in lung tissue and IL-6, tumor necrosis factor-α (TNF-α) in serum were measured by enzyme-linked immunosorbent assay. The Th17 and Treg subset distribution in spleen was determined by flow cytometry. Results Histopathological examination showed that LPS induced inflammatory cell infiltration in lung tissue, increased cell count and protein levels in BALF (P<0.05), and increased proportion of neutrophils and monocytes in the ALI mice. SB203580 significantly attenuated tissue injury of the lungs in LPS-induced ALI mice. Serum levels of IL-6 and TNF-α in the ALI group were significantly higher than those in the control group, and inflammatory cytokines were decreased after SB203580 intervention. Compared with the ALI group, the production of inflammatory cytokines associate with Th17, including IL-17, IL-23, RORγt was inhibited, and the production of cytokines associate with Treg, such as IL-10 and Foxp3 in lung tissue was increased in the intervention group in a concentration-dependent manner with SB203580. After SB203580 intervention, Th17/Treg ratio was significantly decreased compared with the LPS group (P<0.05). Conclusion p38MAPK inhibitor can reduce LPS-induced ALI by regulating the imbalance of Treg cells and Th17 cells.
【Abstract】ObjectiveTo investigate the risk factors for acute lung injury(ALI) after orthotopic liver transplantation(OLT) and to explore the prevention and cure scheme.MethodsThe risk factors responsible for ALI in 4 patients undergoing OLT were analyzed with retrospective investigation.ResultsPortal pulmonary hypertension, longterm mechanical ventilation, severe infection, SIRS, hypercoagulability, overdose transfusion and kidney dysfunction were risk factors for ALI.ConclusionALI frequently occurred after OLT. Reducing and diminishing the risk factors is very important to avoid ALI after OLT.
Objective To investigate the effects and mechanisms of pentoxifylline ( PTX )pretreatment on acute lung injury ( ALI) induced by hemorrhagic shock in mice. Methods Ninety mice were randomly divided into three groups, ie. a control group, a hemorrhagic shock group, and a PTX group.Lung histological changes were examined by HE staining. Meanwhile, the wet-to-dry weight ratio ( W/D) and myeloperoxidase ( MPO) activity in lung were measured. The levels of TNF-αand IL-1βin lung homogenatewere measured by ELISA. The expressions of TLR4 mRNA and TLR4 protein in lung were detected by reverse transcription-polymerase chain reaction ( RT-PCR ) and Western blot, respectively. Results Hemorrhagic shock induced obvious ALI changes in lungs of the hemorrhagic shock group. W/D and MPO activity were significantly higher in the hemorrhagic shock group than the control group( P lt; 0. 01) . The expressions of TNF-α, IL-1β, TLR4 mRNA and TLR4 protein were also significantly higher than the control group( P lt;0. 01) . PTX pretreatment could relieve ALI changes induced by hemorrhagic shock, and decrease W/D and MPO activity. The expressions of TNF-α, IL-1β, TLR4 mRNA and TLR4 protein were also decreased by PTX pretreatment. Conclusions PTX pretreatment shows protective effects on ALI afterhemorrhagic shock. Its possible mechanismmay relate to down-regulation of TLR4, thus inhibit the expression of pro-inflammatory cytokins.
ObjectiveTo observe repairing process of trachea epithelium cells in chlorine-induced airway epithelial injury.MethodsTwelve mice were exposed to chlorine gas and prepared the mice model of airway damage. Three mice were executed respectively on 2nd, 4th, 7th, 10th day after exposure to chlorine gas, and tracheal tissues were collected. In addition 3 normal mice served as control. Airway repair and cell proliferation were detected by EdU labeling method. The basal cell markers keratin 5 (K5), keratin 14 (K14) were adopted as the tracheal epithelial markers for locating the position of the proliferation of repairing cells. Morphological analysis was adopted to measure the proliferation rate as well as the recovery of the false stratified epithelium.ResultsIn the control group, cell proliferation rate was very low, all basal cells expressed K5, and most basal cells did not express K14. Most of epithelial cells shed from the trachea epithelium after exposure to chlorine gas. 2-4 days after chlorine exposure, K5 and K14 expression basal cells increased, K14 expression cells increased greatly. In the peak period of cell proliferation, only a small number of ciliated cells appeared in the repairing trachea area. Epithelial cells repaired fast and widely at the bottom of the trachea.ConclusionThe trachea residual basal cells play roles of progenitor cells and repair the airway epithelium after chlorine damage in mice.
Lung injury could be classified as acute and chronic injuries, such as acute respiratory distress syndrome and chronic obstructive pulmonary disease. Lung function recovery mainly depends on inflammation adjusting, lung and airway remodeling, endogenous stem cell proliferation and differentiation, and tissue repair. The principles of clinical therapy include inhibition of inflammation, balancing coagulation and fibrinolysis, and protective lung ventilation for acute lung injury; while reduction of hyper-secretion, bronchodilation, adjusting airway mucosal inflammation and immunity, as well as improving airway remodeling for chronic obstructive pulmonary disease. The functional recovery of lung and airway depends on endogenous stem cell proliferation and repair. The purpose of clinical treatment is to provide assistance for lung and airway repair besides pathophysiological improvement.
Objective To investigate the expression of granulysin ( GNLY) in lung of rats with acute lung injury ( ALI) stimulated with lipopolysaccharide ( LPS) . Methods Thirty-six healthy adult Wistar rats were randomly divided into a normal control group and a LPS group, with 18 rats in each group. LPS ( 4 mg/kg) was given intraperitoneally in the LPS group to induce ALI. The same amount of normal saline was given in the control group. The rats were randomly assigned to three subgroups ( n = 6) to be sacrificed respectively at 6, 18, and 30 hours after intraperitoneal injection. Wet/dry lung weight ratio ( W/D) and pathological changes of the lung were observed. The expression of GNLY in lung tissue was assayed by immunohistochemistry. Results In the LPS group, the W/D ratio was higher than that of the control group at each time point ( P lt;0. 05) and there were a large number of inflammatory cells infiltration and edema in interstitial spaces which suggested ALI. Compared with the control group, the expression of GNLY in the LPS group was significantly increased at all time points ( P lt;0. 05) . Conclusion GNLY may participate in ALI inflammatory process, which might play a role in preventing infection induced ALI.
ObjectiveTo study the expression of cytokine-induced neutrophil chemoattractant-1(CINC-1)in rats with transfusion-related acute lung injury(TRALI),explore its possible role in the pathogenesis of TRALI. MethodsSixty Sprague-Dawley rats were randomly divided into a normal control group with sham operation,a positive control group with ALI induced by intravenous infusion of lipopolysaccharide(5 mg/kg),and a TRALI group treated by intraperitoneal injection of LPS 2h before the transfusion of human plasma (1mL),a LPS control group treated by intraperitoneal injection of LPS 2h before the transfusion of normal saline(1mL).The reverse transcription-polymerase chain (RT-PCR)was used to detect CINC-1 mRNA.The level of CINC-1 in lung tissue homogenate was measured by ELISA.Morphological changes of the lung tissue were observed under light microscope.Myeloperoxidase (MPO)in lung homogenate and wet lung weight to dry lung weight ratio (W/D)were observed.The number of cells and the percentage of polymorphonuclear neutrophil (PMN)in Bronchoalveolar lavage fluid (BALF)were also compared. ResultsCompared with the normal control group and the LPS control group,the expression of CINC-1 protein and CINC-1 mRNA were increased significantly in lung of the positive control group and the TRALI group(P<0.05).The number of cells and the percentage of PMN in BALF of the TRALI group [(310.63±76.67)×106/L and (33.57±11.51)%] were significantly higher than those in BALF of the normal control group [(101.36±63.83)×106/L and (9.87±3.56)%](P<0.05).Tissue water content and MPO activity in the TRALI group were significantly higher than those in the normal control group (P<0.05). ConclusionExpression of CINC-1 protein and CINC-1 mRNA are increased in the rat lung with TRALI and PMN infiltration in lung tissue,which suggests CINC-1 participate in the process of the PMN and endothelial cell adhesion and may play an important role in the pathogeneses of TRALI.
ObjectiveTo observe the effects of aquaporin 1 (AQP1) on the proliferation and migration of endothelial progenitor-endothelial progenitor cells (EPC).MethodsBone marrow cells of AQP1 wild-type (WT) (n=6) and knockout-type (KO) mice (n=6) were isolated and differentiated into EPC in vitro. Immunofluorescence was used to detect cell surface antigens to identify EPC. Live cell kinetic imaging and quantification technology, transwell migration assays, as well as scratch test were used to compare the function of EPC between AQP1 WT and KO mice.ResultsEPC culture showed that cells were initially suspended and gradually adhered to typical mesenchymal stem cells within 7 days. After cultured on special medium for endothelial cells they were adhered and differentiated, and fusiform or polygonal, paving stone-like EPC were observed around 14 days. When cultured by special medium of EPC, CD133 and CD31 were positively detected after 7 days, and CD34 and Flk-1 were positively detected after 14 days. Positive expression of AQP1 was only detected in EPC of AQP1 WT mice. Functional studies of EPC revealed there was no significant difference in the proliferation of EPC between AQP1 WT and KO group mice. Transwell assay showed that EPC migration ability of AQP1 KO mice was significantly weaker than that of WT mice. The scratch healing ability of EPC in AQP1 KO mice was significantly lower than that of WT mice.ConclusionsEPC initially shows the characteristics of stem cells and with the prolongation of culture time, EPC gradually shows the characteristics of endothelial cells. AQP1 affects the EPC migration rather than proliferation.