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.
Objective To investigate the changes in osteoprotegerin (OPG) / receptor activator of nuclear factor-κB ligand (RANKL) ratio in sepsis-associated acute lung injury (SA-ALI) and the role of regulation of this ratio on the inflammatory response in SA-ALI. Methods Eighteen C57BL/6 male mice were randomly divided into sham operation group, cecal ligation and perforation (CLP) group and RANKL group, with 6 mice in each group. Before the experiment, the RANKL group was intraperitoneally injected with 5 μg (0.2 mL) of recombinant RANKL antibody, whereas both the sham operation group and the CLP group were intraperitoneally injected with a volume-matched normal saline. One hour later, the sham operation group underwent only abdominal exploration and repositioning, while the other groups underwent the CLP surgery to induce the SA-ALI model. After 24 h of modelling, all mice were sacrificed and samples were collected. Pathological evaluation of lung tissues was performed by haematoxylin-eosin staining; enzyme-linked immunosorbent assay was used to detect serum concentrations of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β; while the mRNA and protein expression of OPG and RANKL, along with their ratio values, were detected by real-time polymerase chain reaction for quantitative analysis and protein immunoblotting. Results The SA-ALI mouse model was successfully established. Compared with the sham operation group, mice in the CLP group showed disturbed alveolar structure, obvious alveolar and interstitial haemorrhage and inflammatory cell infiltration, elevated serum levels of IL-6, TNF-α and IL-1β (P<0.05), significantly increased mRNA and protein expression of OPG and elevated OPG/RANKL ratio in lung tissue (P<0.05), whereas RANKL mRNA and protein expression was significantly decreased (P<0.05). Compared with the CLP group, the pathological damage of lung tissue in the RANKL group was reduced, the infiltration of alveolar and interstitial inflammatory cells was significantly improved, and the alveolar structure and morphology were more regular, with lower serum levels of IL-6, TNF-α and IL-1β (P<0.05), significantly lower mRNA and protein expression of OPG and OPG/RANKL ratio in lung tissue (P<0.05), and significantly higher mRNA and protein expression of RANKL in lung tissue (P<0.05). Conclusion The alteration of OPG/RANKL ratio may be related to the pathophysiological process of SA-ALI, and the decrease in its level may reflect the attenuation of the inflammatory response in SA-ALI.
目的 探讨急性百草枯(PQ)中毒鼠肺组织病理损伤和肺组织血红素氧合酶-1（HO-1）的表达及三七总皂甙（PNS）的保护作用。 方法 150只SD雄性鼠分为正常对照组（C组）30只、PQ中毒组（PQ组）60只及PNS组60只。PQ组和PNS组一次性灌胃PQ 25 mg/kg染毒，C组给予等体积生理盐水灌胃。其中PNS组于染毒前15 min以PNS 50 mg/kg阴茎静脉注射保护，以后1次/d给药直至处死前；PQ组、C组分别在同时间点给予等体积生理盐水。观察各组大鼠在中毒后6、12 h，1、3、5、7 d肺组织病理改变，采用蛋白质印迹法分析肺组织HO-1蛋白表达和反转录-聚合酶链反应方法测定鼠肺组织HO-1 mRNA的表达。 结果 C组HO-1蛋白和HO-1 mRNA绝大多数标本有弱表达，个别标本不表达；与C组相比PQ组及PNS组HO-1蛋白和HO-1 mRNA表达增强，差异有统计学意义（P＜0.05）；PQ组HO-1蛋白和HO-1 mRNA的表达在1 d达高峰之后下降，第3天基本恢复到C组水平；PNS组与PQ组相似，但在6 h、12 h、1 d及3 d高于PQ组，差异有统计学意义（P＜0.05），至第5天和第7天二者相比差异无统计学意义（P＜0.05）。PQ组肺组织病理损伤评分在6、12 h，1、3 、5、7 d各亚组均高于PNS相应组，差异有统计学意义（P＜0.05），C组肺组织病理大致正常，与PQ组及PNS组相比，差异有统计学意义（P＜0.001）。 结论 HO-1参与PQ中毒所致急性肺损伤，PNS对PQ中毒所致急性肺损伤有保护作用。
急性肺损伤(acute lung injury,ALI)是临床常见的呼吸系统急危重症,其发病机制复杂,病死率高。肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)是ALI发生、发展过程中非常重要的细胞因子。本文就TNF-α在ALI中的作用和以抗TNF-α为靶点治疗ALI的相关研究进行综述。
Objective To explore the expression of myeloid differentiation protein2 ( MD-2) in rat lung and its role in acute lung injury ( ALI) induced by lipopolysaccharide ( LPS) . Methods Twenty male SD rats were randomly divided into a LPS group and a control group. The wet/dry ratios of lung tissues were measured and the histological changes of lung tissues were observed under microscope. Alveolar macrophages were collected from bronchial alveolar lavage fluid ( BALF) . The MD-2 mRNA and protein expressions were detected by RT-PCR, Western blot, and immunohistochemistry respectively. The MD2-siRNA oligo were transfected into NR8383 cells and 1 μg/mL LPS was used to stimulate the cells. The expressions of MD-2 mRNA and protein were detected by RT-PCR and Western blot. The levels of TNF-αin rat serum and cell culture supernatant were detected by ELISA. Results Compared with the control group, the expressions of MD-2 mRNA and protein in alveolar macrophages and lung tissue were elevated ( P lt;0. 01) , as well as the level of TNF-αin rat serum. The expressions of MD-2 mRNA and protein in NR8383 cell and the level ofTNF-αin supernatant increased obviously after LPS stimulation ( P lt;0. 01) . There were no changes of MD-2 mRNA and protein expressions and TNF-α of NR8383 cells treated by MD-2 siRNA with or without LPS stimulation ( P gt;0. 05) . Conclusions The expression of MD-2 in lung increases obviously after challengedby LPS. KnockdownMD-2 gene of NR8383 cell byMD-2 siRNA can inhibit TNF-αsecretion induced by LPS stimulation.MD-2 may play an important role in rat ALI induced by LPS.
Objective To identify genes of lipopolysaccharide (LPS) -induced acute lung injury (ALI) in mice base on bioinformatics and machine learning. Methods The acute lung injury dataset (GSE2411, GSE111241 and GSE18341) were download from the Gene Expression Database (GEO). Differential gene expression analysis was conducted. Gene ontology (GO) analysis, KEGG pathway analysis, GSEA enrichment analysis and protein-protein interaction analysis (PPI) network analysis were performed. LASSO-COX regression analysis and Support Vector Machine Expression Elimination (SVM-RFE) was utilized to identify key biomarkers. Receiver operator characteristic curve was used to evaluate the diagnostic ability. Validation was performed in GSE18341. Finally, CIBERSORT was used to analyze the composition of immune cells, and immunocorrelation analysis of biomarkers was performed. Results A total of 29 intersection DEGs were obtained after the intersection of GSE2411 and GSE111241 differentially expressed genes. Enrichment analysis showed that differential genes were mainly involved in interleukin-17, cytokine - cytokine receptor interaction, tumor necrosis factor and NOD-like receptor signaling pathways. Machine learning combined with PPI identified Gpx2 and Ifi44 were key biomarkers. Gpx2 is a marker of ferroptosis and Ifi44 is an type I interferon-induced protein, both of which are involved in immune regulation. Immunocorrelation analysis showed that Gpx2 and Ifi44 were highly correlated with Neutrophils, TH17 and M1 macrophage cells. Conclusion Gpx2 and Ifi44 have potential immunomodulatory abilities, and may be potential biomarkers for predicting and treating ALI in mince.
【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 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 concentration of 8-isoprostaglandin ( 8-iso-PG) in exhaled breath condensate ( EBC) of patients with acute lung injury/acute respiratory distress syndrome ( ALI/ ARDS) , and evaluate its clinical significance. Methods Thirty-one ALI/ARDS patients who received mechanical ventilation were recruited as an experimental group, and EBC was collected with improved EcoScreen condenser, while thirty normal subjects were recruited as a control group. The 8-iso-PG level in EBC was analyzed by ELISA. The ALI/ARDS patients were subdivided into a continuous ALI group ( n=10) , a continuous ARDS group ( n=9) , a worsening group ( n=6) , and a remission group ( n=6) by state of illness on 1st day and 5th day. The 8-iso-PG level in EBC of the ALI/ARDS patients with different severity and different prognosis were compared, and the correlation were analyzed between the 8-iso-PG level and clinical indicators. Results The 8-iso-PG levels in EBC of the ALI/ARDS patients on 1st day and 5th day were higher than those in the control subjects respectively [ ( 45.53 ±14.37) ng/L and ( 45.31 ±12.42) ng/L vs. ( 19.47 ±4.06) ng/L, Plt;0.001] . The 8-iso-PG level was higher in the worsening group than the remission group, higher in the continuous ARDS group than the continuous ALI group, and higher in the nonsurvival group than the survival group ( Plt;0.05) . The 8-iso-PG level in EBC was positively correlated with white blood cell count in peripheral blood, lung injury score, X-ray score, AaDO2 /PaO2 , AaDO2 , VT , VE and MEWS score, and negatively correlated with PaO2 /PAO2 and PaO2 /FiO2 . Conclusion The 8-iso-PG level in EBC of ALI/ARDS patients has reference value for judging severity and prognosis of ALI/ARDS.