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.
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（ALI）和急性呼吸窘迫综合征（ARDS）是指由心源性以外的各种肺内外致病因素所导致的急性进行性缺氧性呼吸衰竭，它们具有性质相同的病理生理改变，严重的ALI或ALI的最终严重阶段被定义为ARDS，临床表现以呼吸窘迫、顽固性低氧血症和非心源性肺水肿为特征，采用常规的治疗难以纠正其低氧血症，死亡率高达60%。目前，有关ALI/ARDS的研究取得较多进展，其中，能有效评估ALI病情和预测死亡率的临床参数和生化指标一直是研究热点。
Objective To investigate the pathogenesis of acute lung injury in rats induced by intra-peritoneally injection of perforative peritonitis ascitic fluids（PPAF） and the role of L-arginine （L-Arg） in acute lung injury in this model. Methods Perforative peritonitis （PP） models were established in 60 rats and PPAF were collected. Forty-eight rats were randomly divided equally into NS group，PPAF group, and L-Arg group. Rats were randomly subjected to death at 7 h and 12 h. Peripheral blood WBC were counted，levels of NO and malondialdehyde （MDA） in serum were examined. Lung injury score and wet/dry ratio were evaluated， and level of myeloperoxidase （MPO） in lung tissues and lung cell apoptosis were tested. Results WBC count of peripheral blood, levels of NO and MDA in serum， level of MPO in lung tissue, lung injury score， wet/dry ratio， and lung cell apoptosis rate in PPAF group were significantly higher than that in NS group at each time point（P＜0.01）. Level of NO in serum in L-Arg group was higher than that in PPAF group （P＜0.01）， but lower level of MDA in serum， lower level of MPO in lung tissue and lung injury score，lower wet/dry ratio， and lung cell apoptosis rate were observed in L-Arg group（P＜0.05）. In PPAF group and L-Arg group， level of NO in serum， wet/dry ratio, and lung cell apoptosis rate were higher at 12 h than that at 7 h（P=0.000）. Serum NO level was in negative correlation with serum MDA level （r=-0.257，P=0.021）， MPO level in lung tissue（r=-0.444， P=0.011），and lung cell apoptosis（r=-0.351， P =0.010） in PPAF group and L-Arg group， but serum MDA level was in positive correlation with cell apoptosis（r=0.969， P＜0.001） in each group. Conclusions Acute lung injury rats model can be established by intra-peritoneally injection of PPAF. Enhanced oxidizing reaction and cell apoptosis take part in the occurrence of acute lung injury. L-Arg plays a protective role in acute lung injury.
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.
急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）是临床常见的危重病症，是指非心源性的各种肺内外因素导致的急性进行性呼吸衰竭，临床上以呼吸窘迫，顽固性低氧血症和非心源性肺水肿为特征。急性呼吸窘迫综合征是急性肺损伤的严重阶段。肺微血管通透性增高而导致的肺泡渗出液中富含蛋白质的肺水肿及透明膜形成，并伴有肺间质纤维化由肺内炎症细胞为主导的肺内炎症失控导致的肺泡毛细血管膜损伤形成肺水肿是其共同的病理特征。因此是否能有效清除肺泡内过多液体，维持肺泡腔内相对干燥的环境，对于有效的气体交换具有十分重要的意义，并且在一定程度上决定了病情的转归[1]。
ObjectiveTo investigate the effect of different administration methods of tranexamic acid on postoperative pulmonary inflammation response during cardiopulmonary bypass (CPB).MethodsA total of 64 SD rats were included in the study. They were randomly divided into eight different groups. CPB model was established for the operation groups. The rats in the operation groups were given tranexamic acid at low (25 mg/kg), medium (50 mg/kg) or high (100 mg/kg) concentrations before or after the CPB. Blood cells count and coagulation function were assessed 1 hour after surgery. The concentration of interleukin (IL)-1β、IL-6 and tumor necrosis factor (TNF)-α in blood and lung lavage fluid were measured. The infiltration of inflammatory cells in lungs was observed by hematoxylin-eosin (HE) staining.ResultsThe concentration of inflammatory cells in the operation groups was higher than that in the control group (P<0.05). The use of tranexamic acid inhibited the increase of IL-6 and TNF-α in whole blood and lung lavage fluid due to CPB (P<0.05), but there was no significant difference among the experimental groups (P>0.05). Tranexamic acid could reduce the exudation of inflammatory cells in the lungs.ConclusionThe use of tranexamic acid can effectively reduce the release of inflammatory factors and reduce acute lung injury caused by CPB in rat models. But simply increasing the dose or changing the timing of administration is not more effective in reducing the intensity of the inflammatory response.
ObjectiveTo explore the value of procalcitonin-to-albumin (PAR) in patients with acute respiratory distress syndrome (ARDS).MethodsA retrospective study was carried on patients diagnosed with ARDS from December 2016 to March 2018. The receiver-operating characteristics (ROC) curve was used to identify the cutoff value of PAR. The association of PAR and 28-day mortality was evaluated using univariate and multivariable Cox regression.ResultsIn the final analysis, there were a total of 255 patients included. Of whom 164 (64.3%) was male, 91 (35.7%) was female and the mean age was 52.1±14.5 years old. The 28-day mortality of all the patients was 32.9% (n=84). ROC curve revealed that the cutoff value of PAR was 0.039 (specificity: 0.714, sensitivity: 0.702) and area under the curve was 0.793 (95%CI: 0.735 - 0.850, P<0.001). The following variables were considered for multivariable adjustment: age, body mass index, pneumonia, aspiration, sepsis, surgery, PaO2/FiO2, red blood cell counts and PAR (P<0.01 in univariate analysis). After multivariable analysis, only age (HR: 1.033, 95%CI: 1.009 - 1.059, P=0.008), PaO2/FiO2 (HR: 0.992, 95%CI: 0.985 - 1.000, P=0.044) and PAR (HR: 4.899, 95%CI: 2.148 - 11.174, P<0.001) remained independently associated with 28-day mortality (P<0.05).ConclusionHigh PAR predicts a poor outcome in ARDS patients, therefore it appears to be a prognostic biomarker of outcomes in patients with ARDS.
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.