Objective To study the effects of hyperoxia on ventilator-induced lung injury（VILI） in rats.Methods 48 healthy male SD rats were randomly divided into four groups：Group A received conventional mechanical ventilation（VT=8 mL/kg） with room air，Group B received the same tidal volume as group A with 100% O2，Group C received large tidal volume（VT=40 mL/kg） with room air，group D received the same tidal volume as group C with 100% O2.Arterial blood gases were measured every one hour and oxygenation index（PaO2/FiO2） was calculated.The changes of lung histopathology were assessed by HE staining and observed under light microscope.Wet-to-dry weight ratio（W/D） of left lung，neutrophils and white blood cell（WBC） counts in BALF were measured.TNF-α，IL-1β，and MIP-2 levels in BALF，malondialdehyde（MDA），myeloperoxidase（MPO），and superoxide dismutase（SOD） levels in the lung were assayed，respectively.Results Compared with the Group C，the Group D demonstrated more infiltrating neutrophils in the lung and more destructive changes in the alveolar wall.Meanwhile，the oxygenation index decreased，the WBC and neutrophils counts in BALF increased，and the W/D of left lung was higher in the Group D with significant differences compared with the Group C.Moreover，the BALF levels of TNF-α，IL-1β and MIP-2，the lung levels of MDA increased，and the lung levels of SOD decreased significantly in the Group D compared with those in the Group C.There were no statistical significant differences between the Group B and Group A in all parameters except that MDA levels increased and SOD levels decreased significantly in the Group B.Conclusion Hyperoxia can increase lung injury induced in large tidal volume ventilation in rats，but has mininmal effects in conventional mechanical ventilation.
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 establish a stable and reliable lung injury model caused by severe acute pancreatitis（SAP）in rats， which is helpful to study the acute lung injury （ALI）and acute respiratory distress syndrome （ARDS） induced by SAP.Methods Sixty Sprague-Dawley rats were randomized into ligature group （n=20）， traditional group （n=20），and sham operation group （n=20）. SAP model was established through retrograde injection of 5% taurocholic acid. After injection， the pancreatic duct of rats was ligated in ligature group， but not in traditional group. The lung damage and edema at 24 h after operaton and natural course of rats were observed.Results The ALI model of rats induced by SAP was established successfully in ligature group. The rats died of acute respiratory failure within 48 h in ligature group， the mortality was significantly higher than that in traditional group （100% vs.20%），P＜0.05. Pleural effusion occurred in four rats in ligature group， while no pleural effusion was found in rats in other two groups. The volume of ascites of rats in ligature group was （21.15±5.33） ml， which was more than that in traditional group 〔（7.75±2.66） ml〕，P＜0.05， while no ascites was found in rats in sham operation group. The level of serum amylase of rats in ligature group was （2 470.70±399.73） U/L，which was significantly higher than that in traditional group 〔（1 528.40±289.54） U/L〕 and sham operation group 〔（831.10±93.26） U/L〕，P＜0.001. The level of serum albumin of rats in ligature group was （6.90±1.66）g/L， which was significantly lower than that in traditional group 〔（13.10±0.99） g/L〕 and sham operation group 〔（16.20±0.92） g/L〕，P＜0.001.The lung wet-to-dry weight ratio （W/D） of rats in ligature group was 6.50±0.23， which was greater than that in traditional group （4.92±0.18） and sham operation group （4.61±0.16）， P＜0.001. The score of lung histopathologic of rats in ligature group was 29.25±1.07， which was significantly higher than that in traditional group （12.65±1.98） and sham operation group （0），P＜0.001. The score of pancreas histopathologic of rats in ligature group was 15.95±0.15，which was significantly higher than that in traditional group （13.75±0.66） and sham operation group （0.13±0.29），P＜0.001. Under transmission electron microscope， basement membrane of pulmonary capillary of rats in ligation group was destructive， the nuclei was dissolved， endothelial pinocytotic vesicles was functional active， and tight junctions between capillary endothelial cells were blurred and even ruptured. Moreover， tight junctions between alveolar epithelial cells were destructive. Pathological changes of lung ultrastructure of rats in ligation group were more severe than that in traditional group， while no pathological change of lung ultrastructure was observed in rats in sham operation group. Conclusions Injury process and pathogenesis of ALI or ARDS clinically caused by acute gallstone pancreatitis can be reproduced in this animal model， which is suitable to explore the related mechanisms of ALI caused by SAP and provides good animal model for the study of ALI caused by SAP.
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.
Objective To explore the role of chronic ethanol ingestion in pulmonary fibrosis. Methods Twenty SD rats were randomly divided into a control group (n=10) and an ethanol group ( n=10) , and fed with quantitative non-ethanol and ethanol Lieber-DeCarli liquid diet every day respectively. All rats were sacrificed after 8 weeks. The morphological changes and collagen deposition of lung tissue were observed under light microscope by HE and Masson staining. Levels of glutathione (GSH) and hydroxyproline (HYP) in lung tissues were measured by colorimetric method. The content of connective tissue growth factor (CTGF) in lung tissue was detected by ELISA. Results Compared with the control group, varied degrees of alveolar and alveolar septal infiltration of inflammatory cells can be shown in the ethanol group, and also some alveolar wall damage or collapse.Masson staining showed that the ethanol group has more significant deposition of collagen fibers in alveolar interstitumthan the control group. The content of GSH in rat lung tissue reduced, but the contents of HYP and CTGF increased in the ethanol group compared with the control group [ GSH( mg/g) :0.08±0.04 vs. 0.22±0.14, HYP(mg/g) : 0.57±0.15 vs. 0.40 ± 0.09, CTGF(ng/mL) :306.57±46.86 vs. 134.02±79.82, Plt;0.05] . Conclusions Lieber-DeCarli ethanol liquid diet can establish a rat model of chronic ethanol ingestion. Lung injury and pulmonary fibrosis in rats can be induced by chronic ethanol ingestion. Ethanol may be one of the causes of the pulmonary fibrosis.
Objective To investigate the effects of mechanical ventilation on lung pathology and concentration of proinflammatory cytokines in rats.Methods Forty-five healthy Sprague-Dawley rats were randomly divided into three groups with 15 rats each group，ie.a control group(No mechanical ventilation)，a high tidal volume group(VT 34 mL/kg，RR 30 bpm) and low tidal volume group(VT 8 mL/kg，RR 60 bpm).Results There were enlarged alveolar spaces，interalveolar septum collapse，swollen and spotty hemorrhages，inflammatory cell infiltration in the ventilation groups，which was more serious in the high tidal volume group.Lung wet-to-dry weight ratio of high tidal volume group was significantly higher than that of other groups（both Plt;0.05）.The concentrations in both macrophage-inflammatory protein-2（MIP-2）and tumor necrosis factor-α(TNF-α) of bronchoalveolar lavage fluid(BALF) and blood samples was significantly higher in two ventilation groups than the control group（Plt;0.05），which were higer in the high tidal volume group than in the low tidal volume group（Plt;0.05）.Conclusions These results indicate that mechanical ventilation can cause lung injury，which is more serious in high tidal volume ventilation.And mechanical ventilation-induced lung injury can cause proinflammatory cytokines release，with different levels in bronchoalveolar lavage fluid and blood samples.
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.
ObjectiveThe role of ferroptosis-related genes in the occurrence and development of lung injury caused by sepsis was investigated by bioinformatics methods, and the closely related genes were predicted. MethodsThe Dataset GSE154653 was downloaded from the gene expression database (GEO), and a total of 8 cases of microarray gene set were included in normal group and lipopolysaccharide (LPS)-induced sepsis lung tissue. The differential expression genes (DEGs) were screened out under conditions of |log2 FC|>1 and P.adj<0.05. Meanwhile, the selected DEGs were combined with the driver and suppressor genes of ferroptosis downloaded from the ferroptosis database (FerrDb) to obtain the differential genes associated with ferroptosis in sepsis (Fe-DEGs). These Fe-DEGs were further analyzed using R language, DAVID, and STRING online tools to identify GO-KEGG functions and pathways, and the construction of PPI network. Results The Bioinformatics approach screened out 3533 DEGs and intersected 53 key genes related to ferroptosis. The further biological process (BP) of GO enrichment analysis mainly involves the positive regulation of transcription, the positive regulation of RNA polymerase II promoter transcription, the cytokine mediated signaling pathway, and the positive regulation of angiogenesis. The molecular function (MF) mainly involves the same protein binding, transcriptional activation activity and REDOX enzyme activity. The pathways are enriched in iron death, HIF-1 signaling pathway and AGE-RAGE signaling pathway. Five key Fe-DEGs genes were screened by constructing PPI network, including CYBB, LCN2, HMOX1, TIMP1 and CDKN1A. Conclusion CYBB、LCN2、HMOX1、TIMP1 and CDKNIA genes may be key genes involved in ferroptosis of lung tissue caused by sepsis.
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.