Mogroside IIE,an in vivo metabolite of sweet agent,alleviates acute lung injury via Pla2g2a-EGFR inhibition

In the face of increasingly serious environmental pollution,the health of human lung tissues is also facing serious threats.Mogroside IIE(M2E)is the main metabolite of sweetening agents mogrosides from the anti-tussive Chinese herbal Siraitia grosvenori.The study elucidated the anti-inflammatory action and molecular mechanism of M2E against acute lung injury(ALI).A lipopolysaccharide(LPS)-induced ALI model was established in mice and MH-S cells were employed to explore the protective mechanism of M2E through the western blotting,co-immunoprecipitation,and quantitative real time-PCR analysis.The results indicated that M2E alleviated LPS-induced lung injury through restraining the activation of secreted phospholipase A2 type IIA(Pla2g2a)-epidermal growth factor receptor(EGFR).The interaction of Pla2g2a and EGFR was identified by co-immunoprecipitation.In addition,M2E protected ALI induced with LPS against inflammatory and damage which were significantly dependent upon the downregulation of AKT and m TOR via the inhibition of Pla2g2a-EGFR.Pla2g2a may represent a potential target for M2E in the improvement of LPS-induced lung injury,which may represent a promising strategy to treat ALI.

Research Progress on the Prevention of Premature Infant Lung Injury and Neonatal Respiratory Support

In the past 40 years,advances in neonatal intensive care unit(NICU)technology have enabled premature infants with lower birth weight and younger gestational age to survive.But with it comes an increase in the incidence of long-term respiratory dysfunction,mainly in the form of bronchopulmonary dysplasia(BPD).Preventing lung injury is crucial for preventing BPD and improving the long-term prognosis of premature infants.Therefore,how to avoid ventilator-associated lung injury has become a focus of clinical and scientific research in premature infants in recent years.This article will elaborate on the susceptibility and pathophysiology of premature infant lung injury,ventilation strategies for preventing lung injury,and new advances in neonatal respiratory support.

Periplaneta Americana Extract Ameliorates LPS-induced Acute Lung Injury Via Reducing Inflammation and Oxidative Stress

Objective Acute lung injury(ALI)is an acute clinical syndrome characterized by uncontrolled inflammation response,which causes high mortality and poor prognosis.The present study determined the protective effect and underlying mechanism of Periplaneta americana extract(PAE)against lipopolysaccharide(LPS)-induced ALI.Methods The viability of MH-S cells was measured by MTT.ALI was induced in BALB/c mice by intranasal administration of LPS(5 mg/kg),and the pathological changes,oxidative stress,myeloperoxidase activity,lactate dehydrogenase activity,inflammatory cytokine expression,edema formation,and signal pathway activation in lung tissues and bronchoalveolar lavage fluid(BALF)were examined by H&E staining,MDA,SOD and CAT assays,MPO assay,ELISA,wet/dry analysis,immunofluorescence staining and Western blotting,respectively.Results The results revealed that PAE obviously inhibited the release of proinflammatory TNF-α,IL-6 and IL-1βby suppressing the activation of MAPK/Akt/NF-κB signaling pathways in LPS-treated MH-S cells.Furthermore,PAE suppressed the neutrophil infiltration,permeability increase,pathological changes,cellular damage and death,pro-inflammatory cytokines expression,and oxidative stress upregulation,which was associated with its blockage of the MAPK/Akt/NF-κB pathway in lung tissues of ALI mice.Conclusion PAE may serve as a potential agent for ALI treatment due to its anti-inflammatory and anti-oxidative properties,which correlate to the blockage of the MAPK/NF-κB and AKT signaling pathways.

Glycolysis and acute lung injury:A review

Acute lung injury is featured as diffuse pulmonary edema and persistent hypoxemia caused by lung or systemic injury.It is believed that these pathological changes are associated with damage to the alveolar epithelium and vascular endothelium,recruitment of inflammatory cells,and inflammatory factor storms.In recent years,the metabolic reprogramming of lung parenchymal cells and immune cells,particularly alterations in glycolysis,has been found to occur in acute lung injury.Inhibition of glycolysis can reduce the severity of acute lung injury.Thus,this review focuses on the interconnection between acute lung injury and glycolysis and the mechanisms of interaction,which may bring hope for the treatment of acute lung injury.

Biomarkers Associated with Radiation-Induced Lung Injury in Cancer Patients

Radiotherapy (RT) is a common and effective non-surgical treatment for thoracic solid tumors, and radiation-induced lung injury (RILI) is the most common side effect of radiotherapy. Even if RT is effective in the treatment of cancer patients, severe radiation pneumonitis (RP) or pulmonary fibrosis (PF) can reduce the quality of life of patients and may even lead to serious consequences of death. Therefore, how to overcome the problem of accurate prediction and early diagnosis of RT for pulmonary toxicity is very important. This review summarizes the related factors of RILI and the related biomarkers for early prediction of RILI.

The therapeutic mechanism of dexamethasone in lung injury induced by hydrogen sulfide

The lung is one of the primary target organs of hydrogen sulfide(H2S),as exposure to H2S can cause acute lung injury(ALI)and pulmonary edema.Dexamethasone(Dex)exerts a protective effect on ALI caused by exposure to toxic gases and is commonly used in the clinic;however,the underlying mechanisms remain elusive,and the dose is unclear.Methods:In vivo experiments:divided C57BL6 mice into 6 groups at random,12 in each group.The mice were exposed to H2S for 3 h and 5 or 50 mg/kg Dex pretreated before exposure,sacrificed 12 h later.The morphological changes of HE staining and the ultrastructural changes of lungs under transmission electron microscopy were evaluated.The wet/dry ratio of lung tissue was measured.Bronchial alveolar lavage fluid(BALF)protein content and lung permeability index were detected.The expression of AQP5 protein was measured by immunohistochemistry and Western Blot(WB).In vitro experiments:divided human lung adenocarcinoma cell line A549 into 4 groups.1μmol/L dexamethasone was added to pre-incubation.The WB analyzed the protein of p-ERK1/2,p-JNK,and p-p38 in MAPK pathway after 1 h of NaHS exposure;six hours after NaHS exposure,the AQP5 protein was measured by WB.Results:Dex treatment could significantly attenuate the H2S-induced destruction to the alveolar wall,increase the wet-to-dry weight ratio and decrease pulmonary permeability index,with high-dose dexamethasone seemingly functioning better.Additionally,our previous studies showed that aquaporin 5(AQP 5),a critical protein that regulates water flux,decreased both in a mouse and cell model following the exposure to H2S.This study indicates that tThe decrease in AQP 5 can be alleviated by Dex treatment.Additionally,the mitogen activated protein kinase(MAPK)pathway may be involved in the protective effects of Dex in ALI caused by exposure to H2S since H2Sinduced MAPK activation could be inhibited by Dex.Conclusion:The present results indicate that AQP 5 may be considered a therapeutic target for Dex in H2S or other hazardous gases-induced ALI.

Study of the anti-inflammatory effect of the Traditional Mongolian Medicine Hohgardi-9 in acute lung injury

Background:Hohgardi-9 is a well-known traditional Mongolian drug that relieves cough and removes phlegm.Although it is widely used to treat lung diseases clinically,Hohgardi-9’s bioactive constituents and mechanism of action are unknown.In this study,we explored the bioactive compounds in Hohgardi-9 and the mechanism underlying its therapeutic effect against acute lung injury(ALI).Methods:We obtained the main components of Hohgardi-9 and analyzed the targets related to ALI by searching the traditional Chinese medicine systems pharmacology database and existing literature.Then,we constructed the compound-target network using Cytoscape 3.8.0 software to obtain the bioactive compounds in Hohgardi-9 against ALI.We used a string database to investigate the interaction between the possible protein targets of Hohgardi-9.We also performed Gene Ontology function annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis to predict its anti-ALI mechanism.Further,to verify the therapeutical effects of Hohgardi-9,we used an ALI rat model and analyzed the components of Hohgardi-9 found in the rat plasma using ultra-high-performance liquid chromatography coupled with Q-Exactive mass spectrometry.Results:The network pharmacology and plasma component analysis showed that Hohgardi-9 contained 31 potentially bioactive components,including quercetin,herbacetin,izoteolin,and columbinetin acetate,which affected the NF-κB,TLR,and TNF signaling pathways via key targets,such as RELA(p65)and TLR4.The in vivo experiments using hematoxylin and eosin staining revealed that Hohgardi-9 significantly improved lung tissue injury and pulmonary edema in ALI rats.Simultaneously,Hohgardi-9 significantly reduced the expression levels of genes encoding inflammatory factors,such as TRL4,TNF-α,IL-1β,and ICAM1,in the lungs of ALI rats.Conclusion:Hohgardi-9 alleviated ALI by inhibiting inflammation-related gene expression through its active ingredients,such as quercetin and herbacetin.

Network pharmacology and molecular docking to explore Polygoni Cuspidati Rhizoma et Radix treatment for acute lung injury

BACKGROUND Polygoni Cuspidati Rhizoma et Radix(PCRR),a well-known traditional Chinese medicine(TCM),inhibits inflammation associated with various human diseases.However,the anti-inflammatory effects of PCRR in acute lung injury(ALI)and the underlying mechanisms of action remain unclear.AIM To determine the ingredients related to PCRR for treatment of ALI using multiple databases to obtain potential targets for fishing.METHODS Recognized and candidate active compounds for PCRR were obtained from Traditional Chinese Medicine Systems Pharmacology,STITCH,and PubMed databases.Target ALI databases were built using the Therapeutic Target,DrugBank,DisGeNET,Online Mendelian Inheritance in Man,and Genetic Association databases.Network pharmacology includes network construction,target prediction,topological feature analysis,and enrichment analysis.Bioinformatics resources from the Database for Annotation,Visualization and Integrated Discovery were utilized for gene ontology biological process and Kyoto Encyclopedia of Genes and Genomes network pathway enrichment analysis,and molecular docking techniques were adopted to verify the combination of major active ingredients and core targets.RESULTS Thirteen bioactive compounds corresponding to the 433 PCRR targets were identified.In addition,128 genes were closely associated with ALI,60 of which overlapped with PCRR targets and were considered therapeutically relevant.Functional enrichment analysis suggested that PCRR exerted its pharmacological effects in ALI by modulating multiple pathways,including the cell cycle,cell apoptosis,drug metabolism,inflammation,and immune modulation.Molecular docking results revealed a strong associative relationship between the active ingredient and core target.CONCLUSION PCRR alleviates ALI symptoms via molecular mechanisms predicted by network pharmacology.This study proposes a strategy to elucidate the mechanisms of TCM at the network pharmacology level.

Extracellular vesicles in the pathogenesis and treatment of acute lung injury

Acute lung injury(ALI)and acute respiratory distress syndrome(ARDS)are common life-threatening lung diseases associated with acute and severe inflammation.Both have high mortality rates,and despite decades of research on clinical ALI/ARDS,there are no effective therapeutic strategies.Disruption of alveolar-capillary barrier integrity or activation of inflammatory responses leads to lung inflammation and injury.Recently,studies on the role of extracellular vesicles(EVs)in regulating normal and pathophysiologic cell activities,including inflammation and injury responses,have attracted attention.Injured and dysfunctional cells often secrete EVs into serum or bronchoalveolar lavage fluid with altered cargoes,which can be used to diagnose and predict the development of ALI/ARDS.EVs secreted by mesenchymal stem cells can also attenuate inflammatory reactions associated with cell dysfunction and injury to preserve or restore cell function,and thereby promote cell proliferation and tissue regeneration.This review focuses on the roles of EVs in the pathogenesis of pulmonary inflammation,particularly ALI/ARDS.

Multiomics reveal human umbilical cord mesenchymal stem cells improving acute lung injury via the lung-gut axis

BACKGROUND Acute lung injury(ALI)and its final severe stage,acute respiratory distress syndrome,are associated with high morbidity and mortality rates in patients due to the lack of effective specific treatments.Gut microbiota homeostasis,including that in ALI,is important for human health.Evidence suggests that the gut microbiota improves lung injury through the lung-gut axis.Human umbilical cord mesenchymal cells(HUC-MSCs)have attractive prospects for ALI treatment.This study hypothesized that HUC-MSCs improve ALI via the lung-gut microflora.AIM To explore the effects of HUC-MSCs on lipopolysaccharide(LPS)-induced ALI in mice and the involvement of the lung-gut axis in this process.METHODS C57BL/6 mice were randomly divided into four groups(18 rats per group):Sham,sham+HUC-MSCs,LPS,and LPS+HUC-MSCs.ALI was induced in mice by intraperitoneal injections of LPS(10 mg/kg).After 6 h,mice were intervened with 0.5 mL phosphate buffered saline(PBS)containing 1×10^(6) HUC-MSCs by intraperitoneal injections.For the negative control,100 mL 0.9%NaCl and 0.5 mL PBS were used.Bronchoalveolar lavage fluid(BALF)was obtained from anesthetized mice,and their blood,lungs,ileum,and feces were obtained by an aseptic technique following CO_(2) euthanasia.Wright’s staining,enzyme-linked immunosorbent assay,hematoxylin-eosin staining,Evans blue dye leakage assay,immunohistochemistry,fluorescence in situ hybridization,western blot,16S rDNA sequencing,and non-targeted metabolomics were used to observe the effect of HUC-MSCs on ALI mice,and the involvement of the lung-gut axis in this process was explored.One-way analysis of variance with post-hoc Tukey’s test,independent-sample Student’s t-test,Wilcoxon rank-sum test,and Pearson correlation analysis were used for statistical analyses.RESULTS HUC-MSCs were observed to improve pulmonary edema and lung and ileal injury,and decrease mononuclear cell and neutrophil counts,protein concentrations in BALF and inflammatory cytokine levels in the serum,lung,and ileum of ALI mice.Especially,HUC-MSCs decreased Evans blue concentration and Toll-like receptor 4,myeloid differentiation factor 88,p-nuclear factor kappa-B(NF-κB)/NF-κB,and p-inhibitorαof NF-κB(p-IκBα)/IκBαexpression levels in the lung,and raised the pulmonary vascular endothelial-cadherin,zonula occludens-1(ZO-1),and occludin levels and ileal ZO-1,claudin-1,and occludin expression levels.HUC-MSCs improved gut and BALF microbial homeostases.The number of pathogenic bacteria decreased in the BALF of ALI mice treated with HUCMSCs.Concurrently,the abundances of Oscillospira and Coprococcus in the feces of HUS-MSC-treated ALI mice were significantly increased.In addition,Lactobacillus,Bacteroides,and unidentified_Rikenellaceae genera appeared in both feces and BALF.Moreover,this study performed metabolomic analysis on the lung tissue and identified five upregulated metabolites and 11 downregulated metabolites in the LPS+MSC group compared to the LPS group,which were related to the purine metabolism and the taste transduction signaling pathways.Therefore,an intrinsic link between lung metabolite levels and BALF flora homeostasis was established.CONCLUSION This study suggests that HUM-MSCs attenuate ALI by redefining the gut and lung microbiota.

Acute lung injury and ARDS in acute pancreatitis: Mechanisms and potential intervention

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in acute pancreatitis still represents a substantial problem,with a mortality rate in the range of 30%-40%.The present review evaluates underlying pathophysiological mechanisms in both ALI and ARDS and potential clinical implications.Several mediators and pathophysiological pathways are involved during the different phases of ALI and ARDS.The initial exudative phase is characterized by diffuse alveolar damage,microvascular injury and influx of inflammatory cells.This phase is followed by a fibro-proliferative phase with lung repair,type Ⅱ pneumocyte hypoplasia and proliferation of fibroblasts.Proteases derived from polymorphonuclear neutrophils,various pro-inflammatory mediators,and phospholipases are all involved,among others.Contributing factors that promote pancreatitis-associated ALI may be found in the gut and mesenteric lymphatics.There is a lack of complete understanding of the underlying mechanisms,and by improving our knowledge,novel tools for prevention and intervention may be developed,thus contributing to improved outcome.

Dexmedetomidine Alleviates Pulmonary Edema by Upregulating AQP1 and AQP5 Expression in Rats with Acute Lung Injury Induced by Lipopolysaccharide

This study aims to elucidate the mechanisms by which dexmedetomidine alleviates pulmonary edema in rats with acute lung injury induced by lipopolysaccharide （LPS）. Male Wistar rats were randomly divided into five groups： normal saline control （NS） group, receiving intravenous 0.9% normal saline （5 mL/kg）; LPS group, receiving intravenous LPS （10 mg/kg）; small-dose dexmedetomidine （S） group, treated with a small dose of dexmedetomidine （0.5 μg·kg^-1·h^-1）; medium-dose dexmedetomidine （M） group, treated with a medium dose of dexmedetomidine （2.5 μg·kg^-1·h^-1）; high-dose dexmedetomidine （H） group, treated with a high dose of dexmedetomidine （5μg·kg^-1·h^-1）. The rats were sacrificed 6 h after intravenous injection of LPS or NS, and the hmgs were removed for evaluating histological characteristics and determining the lung wet/dry weight ratio （W/D）. The levels of tumor necrosis factor-alpha （TNF-α） and interleukin-1β （IL-1β） in the lung tissues were assessed by enzyme-linked immunosorbent assay （ELISA）. The mRNA and protein expression levels of aquaporin-1 （AQP1） and aquaporin-5 （AQP5） were detected by RT-PCR, immunohistochemistry, and Western blot- ting. The lung tissues from the LPS groups were significantly damaged, which were less pronounced in the H group but not in the small-dose dexmedetomidine group or medium-dose dexmedetomidine group. The W/D and the concentrations of TNF-α and IL-1β in the pulmonary tissues were increased in the LPS group as compared with those in NS group, which were reduced in the H group but not in S group or M group （P〈0.01）. The expression of AQP1 and AQP5 was lower in the LPS group than in the NS group, and significantly increased in the H group but not in the S group or M group （P〈0.01）. Our findings suggest that dexmedetomidine may alleviate pulmonary edema by increasing the expression of AQP-1 and AQP-5.

Circulating miRNAs as biomarkers for severe acute pancreatitis associated with acute lung injury

AIM To identify circulating micro(mi)RNAs as biological markers for prediction of severe acute pancreatitis(SAP) with acute lung injury(ALI).METHODS Twenty-four serum samples were respectively collected and classified as SAP associated with ALI and SAP without ALI, and the mi RNA expression profiles were determined by microarray analysis. These mi RNAs were validated by quantitative reverse transcriptionpolymerase chain reaction, and their putative targets were predicted by the online software Target Scan, mi Randa and Pic Tar database. Gene ontology(GO) and Kyoto encyclopedia of genes and genomes(commonly known as KEGG) were used to predict their possible functions and pathways involved.RESULTS We investigated 287 mi RNAs based on microarray data analysis. Twelve mi RNAs were differentially expressed in the patients with SAP with ALI and those with SAP without ALI. Hsa-mi R-1260 b, 762, 22-3 p, 23 b and 23 a were differently up-regulated and hsa-mi R-550 a*, 324-5 p, 484, 331-3 p, 140-3 p, 342-3 p and 150 were differently down-regulated in patients with SAP with ALI compared to those with SAP without ALI. In addition, 85 putative target genes of the significantly dysregulated mi RNAs were found by Target Scan, mi Randa and Pic Tar. Finally, GO and pathway network analysis showed that they were mainly enriched in signal transduction, metabolic processes, cytoplasm and cell membranes.CONCLUSION This is the first study to identify 12 circulating mi RNAs in patients with SAP with ALI, which may be biomarkers for prediction of ALI after SAP.

Interleukin-22 ameliorates acute severe pancreatitisassociated lung injury in mice

AIM: To investigate the potential protective effect of exogenous recombinant interleukin-22(r IL-22) on L-arginine-induced acute severe pancreatitis(SAP)-associated lung injury and the possible signaling pathway involved.METHODS: Balb/c mice were injected intraperitoneally with L-arginine to induce SAP. Recombinant mouse IL-22 was then administered subcutaneously to mice. Serum amylase levels and myeloperoxidase(MPO) activity in the lung tissue were measured after the L-arginine administration. Histopathology of the pancreas and lung was evaluated by hematoxylin and eosin(HE) staining. Expression of B cell lymphoma/leukemia-2(Bcl-2), Bcl-x L and IL-22RA1 m RNAs in the lung tissue was detected by real-time PCR. Expression and phosphorylation of STAT3 were analyzed by Western blot. RESULTS: Serum amylase levels and MPO activity in the lung tissue in the SAP group were significantly higher than those in the normal control group(P < 0.05). In addition, the animals in the SAP group showed significant pancreatic and lung injuries. The expression of Bcl-2 and Bcl-x L m RNAs in the SAP group was decreased markedly, while the IL-22RA1 m RNA expression was increased significantly relative to the normal control group(P < 0.05). Pretreatment with PBS did not significantly affect the serum amylase levels, MPO activity or expression of Bcl-2, Bcl-x L or IL-22RA1 m RNA(P > 0.05). Moreover, no significant differences in the degrees of pancreatic and lung injuries were observed between the PBS and SAP groups. However, the serum amylase levels and lung tissue MPO activity in the r IL-22 group were significantly lower than those in the SAP group(P < 0.05), and the injuries in the pancreas and lung were also improved. Compared with the PBS group, r IL-22 stimulated the expression of Bcl-2, Bcl-x L and IL-22RA1 m RNAs in the lung(P < 0.05). In addition, the ratio of p-STAT3 to STAT3 protein in the r IL-22 group was significantly higher than that in the PBS group(P < 0.05).CONCLUSION: Exogenous recombinant IL-22 protects mice against L-arginine-induced SAP-associated lung injury by enhancing the expression of anti-apoptosis genes through the STAT3 signaling pathway.

N-acetylcysteine inhibits activation of toll-like receptor 2 and 4 gene expression in the liver and lung after partial hepatic ischemia-reperfusion injury in mice

BACKGROUND: Toll-like receptor 2 and 4 (TLR2/4) may play important roles in ischemia-reperfusion (I/R) injury, and N-acetylcysteine (NAC) can prevent the generation of reactive oxygen species (ROS) induced by I/R injury. This study aimed to investigate the changes in TLR2/4 gene expression in the liver and lung after I/R injury with or without NAC pretreatment. METHODS: BALB/c mice were used in a model of partial hepatic I/R injury and randomly assigned to a sham-operated control group (SH), a hepatic ischemia/reperfusion group (I/R) or a NAC pretreated, hepatic I/R group (I/R-NAC). The levels of TNF-alpha in the portal vein and plasma alanine aminotransferase (ALT) were measured at 1 and 3 hours after reperfusion. The lung wet-to-dry ratio was measured, and the expression of TLR2/4 mRNA and protein in the liver and lung were assessed with RT-PCR and Western blotting at the same time points. RESULTS: Compared with the I/R group, the expression of TLR2/4 mRNA and protein in the liver and lung in the I/R-NAC group was decreased at the same time point (P<0.05). The levels of portal vein TNF-a and plasma ALT increased continuously in the l/R group at I and 3 hours of reperfusion compared with the SH group; however, they declined significantly in the group pretreated with NAC (P<0.05). The extent of lung edema was relieved in the I/R-NAC group compared with the I/R group (P<0.05). CONCLUSIONS: TLR2/4 was activated in the liver and lung in the process of partial hepatic I/R injury. NAC inhibited the activation of TLR2/4 and the induction of TNF-alpha resulting from I/R injury via modulating the redox state, thus it may mitigate liver and lung injury following partial hepatic I/R in mice.

Synergistic protection of astragalus polysaccharides and matrine against ulcerative colitis and associated lung injury in rats

BACKGROUND Ulcerative colitis(UC)is a main form of inflammatory bowel disease.Due to complicated etiology and a high rate of recurrence,it is quite essential to elucidate the underlying mechanism of and search for effective therapeutic methods for UC.AIM To investigate the effects of astragalus polysaccharides(APS)combined with matrine on UC and associated lung injury.METHODS UC was induced in rats by colon mucosal tissue sensitization combined with trinitro-benzene-sulfonic acid-ethanol.Then,the effects of the treatments of salazopyrine,APS,matrine,and APS combined with matrine on histopathological changes of lung and colon tissues,disease activity index(DAI),colon mucosal damage index(CMDI),serum endotoxin(ET)level,serum diamine oxidase(DAO)activity,the contents of tumor necrosis factor-αand interleukin-1β,and the activities of myeloperoxidase,superoxide dismutase,and malondialdehyde in lung tissues,as well as the protein expression of zonula occludens(ZO)-1,Occludin,and trefoil factor 3(TFF3)were detected in UC rats.RESULTS The treatments of salazopyrine,APS,matrine,and APS combined with matrine reduced DAI scores and improved histopathological changes of colon and lung tissues,as well as decreased CMDI scores,ET levels,and DAO activities in UC rats.Moreover,in lung tissues,inflammatory response and oxidative stress injury were relieved after the treatments of salazopyrine,APS,matrine,and APS combined with matrine in UC rats.Furthermore,the expression of ZO-1,Occludin,and TFF3 in lung and colon tissues was increased after different treatments in UC rats.Notably,APS combined with matrine exerted a better protective effect against UC and lung injury compared with other treatments.CONCLUSION APS combined with matrine exert a synergistic protective effect against UC and lung injury,which might be associated with regulating TFF3 expression.

Cyclooxygenase-2 plays a central role in the genesis of pancreatitis and associated lung injury

BACKGROUND: The exact mechanism by which cyclooxy- genase-2 (COX-2) promotes inflammation in pancreatitis in obscure. This study was undertaken to investigate the role of COX-2 inhibition in an animal model of pancreati- tis , a disease process characterized by a systemic inflamma- tory response and ensuing neutrophil-mediated lung injury. METHODS: Pancreatitis was induced in 24 Sprague-Daw- ley rats by intraperitoneal injection of 20% L-arginine (500 mg/100 g body weight). The animals were randomized into 3 groups (8 rats in each group); controls and rats with pancreatitis intravenously resuscitated with either normal saline (0.9% NaCl 3 ml/kg) at 24 and 48 hours or COX-2 inhibitor (parecoxib 1 mg/kg). Pancreatic and lung inju- ries were assessed histologically. Lung injury was assessed utilizing wet;dry ratio and myeloperoxidase activity to in- dicate pulmonary neutrophil infiltration. A Western blot was used to determine COX-2 protein expression in pancrea- tic tissue. RESULTS: The animals treated with COX-2 inhibitors dis- played significantly less pancreatic and lung injuries than their normal saline counterparts. Histological pancreatic and lung injury scores were significantly reduced (P <0.05) in the COX-2 treated group. Lung wet: dry ratios were sig- nificantly improved and pulmonary neutrophil infiltration was attenuated in the COX-2 group (P<0.05). Western blot analysis confirmed attenuated COX-2 protein expression. CONCLUSION: This study shows, for the first time in a rat model, that adjuvant COX-2 inhibition significandy attenu- ates the severity of both pancreatitis and its associated sys- temic inflammatory response and end-organ injury.

Pathogenesis of acute lung injury in rats with severe acute pancreatitis

BACKGROUND: Acute lung injury (ALI) is the most common and severe complication of severe acute pancreatitis (SAP). The elucidation of the mechanism of ALI contributes to the diagnosis and treatment of the illness. In this study, we studied the pathogenesis of ALI in rats with severe acute pancreatitis. METHODS: The rats were sacrificed at 1, 3, 5, 6, 9 and 12 hours after the establishment of the model of SAP. Pancreas and lung tissues were obtained for pathological study, and examination of microvascular permeability and myeloperoxidase (MPO) examination. The gene expressions of tumor necrosis factor-α (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) in the pancreas and lung tissues were detected by reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: After the establishment of the SAP model, the degree of pancreatic and lung injury increased gradually along with the gradual increase of MPO activity and micro-vascular permeability. Gene expressions of TNF-α and ICAM-1 in the pancreas rose at 1 hour and peaked at 7 hours. In contrast, their gene expression in the lungs rose slightly at 1 hour and peaked at 9-12 hours. CONCLUSION: An obvious time window existed between SAP and lung injury, which is beneficial to the early prevention of the development of ALI.

Ligustrazine alleviates acute lung injury in a rat model of acute necrotizing pancreatitis

BACKGROUND: Acute necrotizing pancreatitis leads to a systemic inflammatory response characterized by widespread leukocyte activation and, as a consequence, distant lung injury. The aim of this study was to evaluate the effect of ligustrazine, extracted from Ligusticum wallichii a traditional Chinese medicine, on lung injury in a rat model of acute necrotizing pancreatitis (ANP). METHODS: A total of 192 rats were randomly divided into three groups: control (C group); ANP without treatment (P group); and ANP treated with ligustrazine (T group). Each group was further divided into 0.5, 2, 6 and 12 hours subgroups. All rats were anesthetized with an intraperitoneal injection of sodium pentobarbital. Sodium taurocholate was infused through the pancreatic membrane to induce ANP. For the T group, sodium taurocholate was infused as above, then 0.6% ligustrazine was administered via the femoral vein. The effects of ligustrazine on the severity of lung injury were assessed by lung wet/dry weight ratio, myeloperoxidase (MPO) activity and histopathological changes. Pulmonary blood flow was determined by the radioactive microsphere technique (RMT). RESULTS: The blood flow in the P group was significantly lower than that of the C group, while the blood flow in the T group was significantly higher than that of the P group but showed no significant difference from the C group. Compared with C group, the lung wet/dry ratios in both the P and T groups were significantly increased, but there was no significant difference between them. The MPO activity in the P group was greatly increased over that of the C group. In the T group, although the MPO activity was also higher than in the C group, it much less increased than in the P group. Moreover, the difference between P and T groups was significant after 0.5 to 12 hours. After induction of the ANP model, the pancreas showed mild edema and congestion; the longer the time, the more severe this became. The pulmonary pathological changes wereaggravated significantly in the P group. Histopathological scores were higher in the P group than in the C group throughout the experimental course. Histopathological scores in the T group were lower than those in the P group at 6 and 12 hours. CONCLUSIONS: Microcirculatory disorder is an important factor of lung injury in ANP. Ligustrazine can ameliorate microcirculatory disorder and alleviate the damage to the lung.

Involvement of apoptosis of alveolar epithelial cells in acute pancreatitis-associated lung injury

INTRODUCTIONAcute pancreatitis in a common and potentially fataldisease which is associated with considerablemorbidity and a mortality rate of approximately30%;its pathogenesis remains unknown.Thecause of death is often due to multiple organ