AIM： To investigate the role of nuclear factor kappa B （NF-κB） in the pathogenesis of lung injury induced by intestinal ischemia/reperfusion （I/R）, and its effect on intercellular adhesion molecule-1 （ICAM-1） ...AIM： To investigate the role of nuclear factor kappa B （NF-κB） in the pathogenesis of lung injury induced by intestinal ischemia/reperfusion （I/R）, and its effect on intercellular adhesion molecule-1 （ICAM-1） expression and neutrophil infiltration. METHODS： Twenty-four Wistar rats were divided randomly into control, I/R and pyrrolidine dithiocarbamate （PDTC） treatment groups, n = 8 in each. I/R group and PDTC treatment group received superior mysenteric artery （SMA） occluding for 1 h and reperfusion for 2 h. PDTC group was administrated with intraperitoneal injection of 2% 100 mg/kg PDTC 1 h before surgery. Lung histology and bronchia alveolus lung fluid （BALF） protein were assayed. Serum IL-6, lung malondialdehyde （MDA） and myeloperoxidase （MPO） as well as the expression level of NF-κB and ICAM-1 were measured.RESULTS： Lung injury induced by intestinal I/R, was characterized by edema, hemorrhage and neutrophil infiltration as well as by the significant rising of BALF protein. Compared to control group, the levels of serum IL-6 and lung MDA and MPO increased significantly in I/R group （P=0.001）. Strong positive expression of NF-κB p65 and ICAM-1 was observed. After the administration of PDTC, the level of serum IL-6, lung MDA and MPO as well as NF-κB and ICAM-1 decreased significantly （P〈 0.05） when compared to I/R group.CONCLUSION： The activation of NF-κB plays an important role in the pathogenesis of lung injury induced by intestinal I/R through upregulating the neutrophil infiltration and lung ICAM-1 expression. PDTC as an inhibitor of NF-κB can prevent lung injury induced by intestinal I/R through inhibiting the activity of NF-κB.展开更多
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 inju...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.展开更多
In order to provide us new clues to induce some endogenous protective molecular mechanisms, the changes in gene expression profile induced by ischemia-reperfusion in pulmonary tissues of rats were investigated and the...In order to provide us new clues to induce some endogenous protective molecular mechanisms, the changes in gene expression profile induced by ischemia-reperfusion in pulmonary tissues of rats were investigated and the dynamic mechanism of pulmonary ischemia-reperfusion injury was elucidated. Thirty male Wistar rats were randomly divided into 6 groups： 5 ischemia-reperfusion （I/R） groups （I/R 0-h, I/R 1-h, I/R 3-h, I/R 6-h, I/R 24-h） and control group （n=5 in each）. An in situ ischemia-reperfusion lung injury rat model was established by occluded hilus of lung. The RatRef-12 Expression Beadchip （22 226 gene probes per array） was used to analyze the pattern of gene expression in all groups. The results showed that 648, 340, 711, 1279 and 641 genes were differentially expressed in I/R 0-, 1-, 3-, 6- and 24-h groups respectively. The differentially expressed genes were classified as following 7 functional categories： cytokine, adhesion molecule, growth factor and apoptosis-related factor, oxidation and antioxidation molecule, metabolic enzyme, ion channel and aquaporin, signal transduction molecule. It was suggested that gene chip technology was an effective and quick method for screening differentially expressed genes. Many differentially expressed genes with different functions interacted each other to result in pulmonary ischemia-reperfusion injury.展开更多
Objective:To study the protective effect of resveratrol on secondary lung injury in intestinal ischemia reperfusion and its effect on P38MAPK pathway.Methods:Adult male SPF SD rats were selected and divided into contr...Objective:To study the protective effect of resveratrol on secondary lung injury in intestinal ischemia reperfusion and its effect on P38MAPK pathway.Methods:Adult male SPF SD rats were selected and divided into control group, I/R group, Res-L group, Res-M group and Res-H group, the small intestinal ischemia reperfusion model was made, and Res-L group, Res-M group and Res-H group were given 5.0 mg/kg, 10.0 mg/kg and 15.0 mg/kg resveratrol for intervention. The contents of P38MAPK pathway molecules as well as downstream apoptotic molecules, inflammatory factors and oxidative stress products in the lung were detected.Results:P38MAPK, MAPKK, MAPKKK, Fas, FasL, caspase-8, caspase-9, NF-kB, TNF- and IL-1β expression as well as ROS and MDA contents in lung tissue of I/R group were significantly higher than those of control group;P38MAPK, MAPKK, MAPKKK, Fas, FasL, caspase-8, caspase-9, NF-kB, TNF-α and IL-1β expression as well as ROS and MDA contents in lung tissue of Res-L group, Res-M group and Res-H group were significantly lower than those of I/R group.Conclusion: Resveratrol can inhibit the function of P38MAPK pathway to reduce apoptosis, inflammation and oxidative stress, and then protect the secondary lung injury induced by intestinal ischemia reperfusion.展开更多
Objective To investigate the expression of bradykinin as a substrate of CD26 /DPP IV in rats with ischemia/reperfusion injury following lung transplantation ( LTx) . Methods Thirty - six syngeneic male SD rats were ra...Objective To investigate the expression of bradykinin as a substrate of CD26 /DPP IV in rats with ischemia/reperfusion injury following lung transplantation ( LTx) . Methods Thirty - six syngeneic male SD rats were randomly allocated into control group and experimental group ( n = 18 each) ,and 36 rats served as do-展开更多
Objective： To explore the expression and meaning of Toll-like receptor 2/4 in alveolar macrophage during the process of total hepatic ischemia in mice. Methods： BALB/c mice were used in a model of total hepatic isch...Objective： To explore the expression and meaning of Toll-like receptor 2/4 in alveolar macrophage during the process of total hepatic ischemia in mice. Methods： BALB/c mice were used in a model of total hepatic ischemia/reperfusion. Alveolar Macrophage were collected at the time point of lh, 6h and 12h by the means of bronchoalveolar lavage （BAL）, and its TLR2/4 mRNA and protein were detected with Flow Cytometry and Real-time PCR. The level of TNF in BAL fluid were measured. The concentration of MPO, the ratio of wet/dry and lung histological scores were used to assess the degrees of lung injuries. Results： At the three time points of hepatic ischemia reperfusion, the expression of TLR2/4 protein of and mRNA were up-regulated and the level of TLR2 was on the rise continually. TLR4 at the time of 6 h reached the peak value （P〈0.01）. The level of TNF-2 in BAL fluid reached the highest point at the time of 6 h （P〈0.01）. The ratio of wet/dry rose continually during hepatic ischemia reperfusion. After 1 h, the level of MPO increased rapidly. Then it reached the peak value during the period of 6 h to 12 h. Conclusion： TLR2/4 on the mice of alveolar macrophage were activated in the process of hepatic ischemia/reperfusion and involved in the injury of lung.展开更多
Background The composition of the lung preservation solution used in lung graft procurement has been considered the key to minimize lung injury during the period of ischemia. Low-potassium dextran glucose （LPDG）, an...Background The composition of the lung preservation solution used in lung graft procurement has been considered the key to minimize lung injury during the period of ischemia. Low-potassium dextran glucose （LPDG）, an extracellular-type solution, has been adopted by most lung transplantation centers, due to the experimental and clinical evidences that LPDG is superior to intracellular-type solutions. Ulinastatin has been shown to attenuate ischemia-reperfusion （I/R） injury in various organs in animals. We supposed that the addition of ulinastatin to LPDG as a flushing solution, would further ameliorate I/R lung injury than LPDG solution alone.Methods Twelve male New Zealand white rabbits were randomly divided into 2 groups. Using an alternative in situ lung I/R model, the left lung in the control group was supplied and preserved with LPDG solution for 120 minutes. In the study group 50 000 U/kg of ulinastatin was added to the LPDG solution for lung preservation. Then re-ventilation and reperfusion of the left lung were performed for 90 minutes. Blood gas analysis （PaO2, PaCO2）, mean pulmonary artery pressure （MPAP） and serum TNF-α level were measured intermittently. The pulmonary water index （D/W）, tissue myeloperoxidase （MPO） activity, tissue malondialdehyde （MDA） content and morphologic changes were analyzed.Results The study group showed significantly higher PaO2 and lower MPAP at the end of reperfusion. Serum TNF-α level, left lung tissue MPO and MDA in the study group were significantly lower than those in the control group. D/W and pathologic evaluation were also remarkably different between the two groups.Conclusions This study indicated that better lung preservation could be achieved with the use of an ulinastatin modified LPDG solution. Ulinastatin further attenuated lung I/R injury, at least partly by reducing oxidative reactions,inhibiting the release of inflammatory factors and neutrophils immigration.展开更多
Brain damage can cause lung injury. To explore the mechanism underlying the lung injury induced by acute cerebral ischemia(ACI), we established a middle cerebral artery occlusion(MCAO) model in male Sprague-Dawley rat...Brain damage can cause lung injury. To explore the mechanism underlying the lung injury induced by acute cerebral ischemia(ACI), we established a middle cerebral artery occlusion(MCAO) model in male Sprague-Dawley rats. We focused on glia maturation factor b(GMFB) based on quantitative analysis of the global rat serum proteome.Polymerase chain reaction, western blotting, and immunofluorescence revealed that GMFB was overexpressed in astrocytes in the brains of rats subjected to MCAO. We cultured rat primary astrocytes and confirmed that GMFB was also up-regulated in primary astrocytes after oxygen-glucose deprivation(OGD). We subjected the primary astrocytes to Gmfb RNA interference before OGD and collected the conditioned medium(CM) after OGD.We then used the CM to culture pulmonary microvascular endothelial cells(PMVECs) acquired in advance and assessed their status. The viability of the PMVECs improved significantly when Gmfb was blocked. Moreover,ELISA assays revealed an elevation in GMFB concentration in the medium after OGD. Cell cultures containing recombinant GMFB showed increased levels of reactive oxygen species and a deterioration in the state of the cells.In conclusion, GMFB is up-regulated in astrocytes after ACI, and brain-derived GMFB damages PMVECs by increasing reactive oxygen species. GMFB might thus be an initiator of the lung injury induced by ACI.展开更多
End-stage lung diseases are common and frequentlyoccurring diseases which are difficult for clinical treatment. In recent years, lung transplantation has become a widely accepted and effective therapeutic option for p...End-stage lung diseases are common and frequentlyoccurring diseases which are difficult for clinical treatment. In recent years, lung transplantation has become a widely accepted and effective therapeutic option for patients with the end-stage pulmonary diseases. Early pulmonary edema resulting from ischemia-reperfusion injury accounts for the major part of mortality and morbidity after lung transplantation. The water channel proteins in lung injury have been little studied, and their impact on the formation of pulmonary edema remains unclear. In this study, we established a rat lung ischemia-reperfusion model to study its impact on the expressions of water channel proteins in lung tissue and explore a new approach to lung transplantation in pulmonary edema pathogenesis.展开更多
Background Previous reports have confirmed that edaravone has protective effects against ischemia-reperfusion （IR） injury of many organs. In this study, we investigated the effect of edaravone on preventing IR injur...Background Previous reports have confirmed that edaravone has protective effects against ischemia-reperfusion （IR） injury of many organs. In this study, we investigated the effect of edaravone on preventing IR injury of the lung in a canine lung transplantation model. Methods Twelve weight-matched pairs of random-bred dogs were randomized into two groups. Within each pair, one dog served as donor and the other as recipient. In the study group, prostaglandin EI（PGE1）（8 μg/kg） was injected into the donor pulmonary artery （PA） before occlusion and the donor lungs were flushed with 1.0 L of LPD solution containing edaravone （10 mg/kg） and stored in the same LPD solution at a temperature of 1℃for 8 hours. The left single lung transplantation was then performed and recipients received intravenous injection with edaravone （10 mg/kg） at the onset of reperfusion. In the control group, edaravone was substituted by the same volume of sterile saline solution. Another six dogs were obtained as normal control group in which left lungs were dissected after thoracotomy without an IR injury. One hour after reperfusion, or after dissection of the left lung, the right lung was excluded from perfusion and ventilation after which, cardiopulmonary parameters were measured. Wet/dry ratios, malondialdehyde （MDA） and myeloperoxidase （MPO） levels were assessed and histological analysis of lung tissue performed at the same time. Results All animals survived until the end of the experiment. The study group showed significantly decreased wet/dry ratios （treated： （74.1±4.2）% vs control： （86.8±5.2）%, P 〈0.01）, MDA levels （treated： 0.50±0.08 vs control： 0.88±0.15, P 〈0.01） and MPO activity （treated： 0.23±0.05 vs control： 0.43±0.07, P 〈0.01） compared to the control group two hours after occlusion of the right side. In the control group, pulmonary vascular resistance （PVR） was increased markedly and arterial oxygen partial pressure deteriorated significantly after exclusion of the right side compared to those in the treatment group. Conclusions Edaravone attenuates IR-induced lung injury and preserves lung function by inhibiting oxidative stress and decreasing leukocyte extravasation in a canine lung transplantation model.展开更多
Background：Biliverdin （BV） has a protective role against ischemia-reperfusion injury （IRI）.However,the protective role and potential mechanisms of BV on lung IRI （LIRI） remain to be elucidated.Thus,we aimed to ...Background：Biliverdin （BV） has a protective role against ischemia-reperfusion injury （IRI）.However,the protective role and potential mechanisms of BV on lung IRI （LIRI） remain to be elucidated.Thus,we aimed to investigate the protective role and potential mechanisms of BV on LIRI.Methods：Lungs were isolated from Sprague-Dawley rats to establish an ex vivo LIRI model.After an initial 15 min stabilization period,the isolated lungs were subjected to ischemia for 60 min,followed by 90 min ofreperfusion with or without BV treatment.Results：Lungs in the I/R group exhibited significant decrease in tidal volume （1.44 ± 0.23 ml/min in I/R group vs.2.41 ± 0.31 ml/min in sham group;P 〈 0.001）,lung compliance （0.27 ± 0.06 ml/cmH2O in I/R group vs.0.44 ± 0.09 ml/cmH2O in sham group;P 〈 0.001;1 cmH2O=0.098 kPa）,and oxygen partial pressure （PaO2） levels （64.12 ± 12 mmHg in FR group vs.114 ± 8.0 mmHg in sham group;P 〈 0.001;1 mmHg =0.133 kPa）.In contrast,these parameters in the BV group （2.27 ± 0.37 ml/min of tidal volume,0.41 ± 0.10 ml/ cmH2O of compliance,and 98.7 ± 9.7 mmHg of PaO2） were significantly higher compared with the I/R group （P =0.004,P 〈 0.001,and P 〈 0.001,respectively）.Compared to the I/R group,the contents of superoxide dismutase were significantly higher （47.07 ± 7.91 U/mg protein vs.33.84 ± 10.15 U/mg protein;P =0.005） while the wet/dry weight ratio （P 〈 0.01）,methane dicarboxylic aldehyde （1.92 ± 0.25 nmol/mg protein vs.2.67 ± 0.46 nmol/mg protein;P 〈 0.001）,and adenosine triphosphate contents （297.05 ± 47.45 nmol/mg protein vs.208.09 ± 29.11 nmol/mg protein;P =0.005） were markedly lower in BV-treated lungs.Histological analysis revealed that BV alleviated LIRI.Furthermore,the expression of inflammatory cytokines （interleukin-1 β,interleukin-6,and tumor necrosis factor-α） was downregulated and the expression of cyclooxygenase-2,inducible nitric oxide synthase,and Jun N-terminal kinase was significantly reduced in BV group （all P 〈 0.01 compared to I/R group）.Finally,the apoptosis index in the BV group was significantly decreased （P 〈 0.01 compared to I/R group）.Conclusion：BV protects lung IRI through its antioxidative,anti-inflammatory,and anti-apoptotic effects.展开更多
基金Supported by The Natural Science Foundation of Liaoning Province,No.20042135
文摘AIM： To investigate the role of nuclear factor kappa B （NF-κB） in the pathogenesis of lung injury induced by intestinal ischemia/reperfusion （I/R）, and its effect on intercellular adhesion molecule-1 （ICAM-1） expression and neutrophil infiltration. METHODS： Twenty-four Wistar rats were divided randomly into control, I/R and pyrrolidine dithiocarbamate （PDTC） treatment groups, n = 8 in each. I/R group and PDTC treatment group received superior mysenteric artery （SMA） occluding for 1 h and reperfusion for 2 h. PDTC group was administrated with intraperitoneal injection of 2% 100 mg/kg PDTC 1 h before surgery. Lung histology and bronchia alveolus lung fluid （BALF） protein were assayed. Serum IL-6, lung malondialdehyde （MDA） and myeloperoxidase （MPO） as well as the expression level of NF-κB and ICAM-1 were measured.RESULTS： Lung injury induced by intestinal I/R, was characterized by edema, hemorrhage and neutrophil infiltration as well as by the significant rising of BALF protein. Compared to control group, the levels of serum IL-6 and lung MDA and MPO increased significantly in I/R group （P=0.001）. Strong positive expression of NF-κB p65 and ICAM-1 was observed. After the administration of PDTC, the level of serum IL-6, lung MDA and MPO as well as NF-κB and ICAM-1 decreased significantly （P〈 0.05） when compared to I/R group.CONCLUSION： The activation of NF-κB plays an important role in the pathogenesis of lung injury induced by intestinal I/R through upregulating the neutrophil infiltration and lung ICAM-1 expression. PDTC as an inhibitor of NF-κB can prevent lung injury induced by intestinal I/R through inhibiting the activity of NF-κB.
基金This work was supported by a grant from theNational Natural Science Foundation of China(No.30200272).
文摘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.
文摘In order to provide us new clues to induce some endogenous protective molecular mechanisms, the changes in gene expression profile induced by ischemia-reperfusion in pulmonary tissues of rats were investigated and the dynamic mechanism of pulmonary ischemia-reperfusion injury was elucidated. Thirty male Wistar rats were randomly divided into 6 groups： 5 ischemia-reperfusion （I/R） groups （I/R 0-h, I/R 1-h, I/R 3-h, I/R 6-h, I/R 24-h） and control group （n=5 in each）. An in situ ischemia-reperfusion lung injury rat model was established by occluded hilus of lung. The RatRef-12 Expression Beadchip （22 226 gene probes per array） was used to analyze the pattern of gene expression in all groups. The results showed that 648, 340, 711, 1279 and 641 genes were differentially expressed in I/R 0-, 1-, 3-, 6- and 24-h groups respectively. The differentially expressed genes were classified as following 7 functional categories： cytokine, adhesion molecule, growth factor and apoptosis-related factor, oxidation and antioxidation molecule, metabolic enzyme, ion channel and aquaporin, signal transduction molecule. It was suggested that gene chip technology was an effective and quick method for screening differentially expressed genes. Many differentially expressed genes with different functions interacted each other to result in pulmonary ischemia-reperfusion injury.
文摘Objective:To study the protective effect of resveratrol on secondary lung injury in intestinal ischemia reperfusion and its effect on P38MAPK pathway.Methods:Adult male SPF SD rats were selected and divided into control group, I/R group, Res-L group, Res-M group and Res-H group, the small intestinal ischemia reperfusion model was made, and Res-L group, Res-M group and Res-H group were given 5.0 mg/kg, 10.0 mg/kg and 15.0 mg/kg resveratrol for intervention. The contents of P38MAPK pathway molecules as well as downstream apoptotic molecules, inflammatory factors and oxidative stress products in the lung were detected.Results:P38MAPK, MAPKK, MAPKKK, Fas, FasL, caspase-8, caspase-9, NF-kB, TNF- and IL-1β expression as well as ROS and MDA contents in lung tissue of I/R group were significantly higher than those of control group;P38MAPK, MAPKK, MAPKKK, Fas, FasL, caspase-8, caspase-9, NF-kB, TNF-α and IL-1β expression as well as ROS and MDA contents in lung tissue of Res-L group, Res-M group and Res-H group were significantly lower than those of I/R group.Conclusion: Resveratrol can inhibit the function of P38MAPK pathway to reduce apoptosis, inflammation and oxidative stress, and then protect the secondary lung injury induced by intestinal ischemia reperfusion.
文摘Objective To investigate the expression of bradykinin as a substrate of CD26 /DPP IV in rats with ischemia/reperfusion injury following lung transplantation ( LTx) . Methods Thirty - six syngeneic male SD rats were randomly allocated into control group and experimental group ( n = 18 each) ,and 36 rats served as do-
文摘Objective： To explore the expression and meaning of Toll-like receptor 2/4 in alveolar macrophage during the process of total hepatic ischemia in mice. Methods： BALB/c mice were used in a model of total hepatic ischemia/reperfusion. Alveolar Macrophage were collected at the time point of lh, 6h and 12h by the means of bronchoalveolar lavage （BAL）, and its TLR2/4 mRNA and protein were detected with Flow Cytometry and Real-time PCR. The level of TNF in BAL fluid were measured. The concentration of MPO, the ratio of wet/dry and lung histological scores were used to assess the degrees of lung injuries. Results： At the three time points of hepatic ischemia reperfusion, the expression of TLR2/4 protein of and mRNA were up-regulated and the level of TLR2 was on the rise continually. TLR4 at the time of 6 h reached the peak value （P〈0.01）. The level of TNF-2 in BAL fluid reached the highest point at the time of 6 h （P〈0.01）. The ratio of wet/dry rose continually during hepatic ischemia reperfusion. After 1 h, the level of MPO increased rapidly. Then it reached the peak value during the period of 6 h to 12 h. Conclusion： TLR2/4 on the mice of alveolar macrophage were activated in the process of hepatic ischemia/reperfusion and involved in the injury of lung.
文摘Background The composition of the lung preservation solution used in lung graft procurement has been considered the key to minimize lung injury during the period of ischemia. Low-potassium dextran glucose （LPDG）, an extracellular-type solution, has been adopted by most lung transplantation centers, due to the experimental and clinical evidences that LPDG is superior to intracellular-type solutions. Ulinastatin has been shown to attenuate ischemia-reperfusion （I/R） injury in various organs in animals. We supposed that the addition of ulinastatin to LPDG as a flushing solution, would further ameliorate I/R lung injury than LPDG solution alone.Methods Twelve male New Zealand white rabbits were randomly divided into 2 groups. Using an alternative in situ lung I/R model, the left lung in the control group was supplied and preserved with LPDG solution for 120 minutes. In the study group 50 000 U/kg of ulinastatin was added to the LPDG solution for lung preservation. Then re-ventilation and reperfusion of the left lung were performed for 90 minutes. Blood gas analysis （PaO2, PaCO2）, mean pulmonary artery pressure （MPAP） and serum TNF-α level were measured intermittently. The pulmonary water index （D/W）, tissue myeloperoxidase （MPO） activity, tissue malondialdehyde （MDA） content and morphologic changes were analyzed.Results The study group showed significantly higher PaO2 and lower MPAP at the end of reperfusion. Serum TNF-α level, left lung tissue MPO and MDA in the study group were significantly lower than those in the control group. D/W and pathologic evaluation were also remarkably different between the two groups.Conclusions This study indicated that better lung preservation could be achieved with the use of an ulinastatin modified LPDG solution. Ulinastatin further attenuated lung I/R injury, at least partly by reducing oxidative reactions,inhibiting the release of inflammatory factors and neutrophils immigration.
文摘Brain damage can cause lung injury. To explore the mechanism underlying the lung injury induced by acute cerebral ischemia(ACI), we established a middle cerebral artery occlusion(MCAO) model in male Sprague-Dawley rats. We focused on glia maturation factor b(GMFB) based on quantitative analysis of the global rat serum proteome.Polymerase chain reaction, western blotting, and immunofluorescence revealed that GMFB was overexpressed in astrocytes in the brains of rats subjected to MCAO. We cultured rat primary astrocytes and confirmed that GMFB was also up-regulated in primary astrocytes after oxygen-glucose deprivation(OGD). We subjected the primary astrocytes to Gmfb RNA interference before OGD and collected the conditioned medium(CM) after OGD.We then used the CM to culture pulmonary microvascular endothelial cells(PMVECs) acquired in advance and assessed their status. The viability of the PMVECs improved significantly when Gmfb was blocked. Moreover,ELISA assays revealed an elevation in GMFB concentration in the medium after OGD. Cell cultures containing recombinant GMFB showed increased levels of reactive oxygen species and a deterioration in the state of the cells.In conclusion, GMFB is up-regulated in astrocytes after ACI, and brain-derived GMFB damages PMVECs by increasing reactive oxygen species. GMFB might thus be an initiator of the lung injury induced by ACI.
文摘End-stage lung diseases are common and frequentlyoccurring diseases which are difficult for clinical treatment. In recent years, lung transplantation has become a widely accepted and effective therapeutic option for patients with the end-stage pulmonary diseases. Early pulmonary edema resulting from ischemia-reperfusion injury accounts for the major part of mortality and morbidity after lung transplantation. The water channel proteins in lung injury have been little studied, and their impact on the formation of pulmonary edema remains unclear. In this study, we established a rat lung ischemia-reperfusion model to study its impact on the expressions of water channel proteins in lung tissue and explore a new approach to lung transplantation in pulmonary edema pathogenesis.
文摘Background Previous reports have confirmed that edaravone has protective effects against ischemia-reperfusion （IR） injury of many organs. In this study, we investigated the effect of edaravone on preventing IR injury of the lung in a canine lung transplantation model. Methods Twelve weight-matched pairs of random-bred dogs were randomized into two groups. Within each pair, one dog served as donor and the other as recipient. In the study group, prostaglandin EI（PGE1）（8 μg/kg） was injected into the donor pulmonary artery （PA） before occlusion and the donor lungs were flushed with 1.0 L of LPD solution containing edaravone （10 mg/kg） and stored in the same LPD solution at a temperature of 1℃for 8 hours. The left single lung transplantation was then performed and recipients received intravenous injection with edaravone （10 mg/kg） at the onset of reperfusion. In the control group, edaravone was substituted by the same volume of sterile saline solution. Another six dogs were obtained as normal control group in which left lungs were dissected after thoracotomy without an IR injury. One hour after reperfusion, or after dissection of the left lung, the right lung was excluded from perfusion and ventilation after which, cardiopulmonary parameters were measured. Wet/dry ratios, malondialdehyde （MDA） and myeloperoxidase （MPO） levels were assessed and histological analysis of lung tissue performed at the same time. Results All animals survived until the end of the experiment. The study group showed significantly decreased wet/dry ratios （treated： （74.1±4.2）% vs control： （86.8±5.2）%, P 〈0.01）, MDA levels （treated： 0.50±0.08 vs control： 0.88±0.15, P 〈0.01） and MPO activity （treated： 0.23±0.05 vs control： 0.43±0.07, P 〈0.01） compared to the control group two hours after occlusion of the right side. In the control group, pulmonary vascular resistance （PVR） was increased markedly and arterial oxygen partial pressure deteriorated significantly after exclusion of the right side compared to those in the treatment group. Conclusions Edaravone attenuates IR-induced lung injury and preserves lung function by inhibiting oxidative stress and decreasing leukocyte extravasation in a canine lung transplantation model.
文摘Background：Biliverdin （BV） has a protective role against ischemia-reperfusion injury （IRI）.However,the protective role and potential mechanisms of BV on lung IRI （LIRI） remain to be elucidated.Thus,we aimed to investigate the protective role and potential mechanisms of BV on LIRI.Methods：Lungs were isolated from Sprague-Dawley rats to establish an ex vivo LIRI model.After an initial 15 min stabilization period,the isolated lungs were subjected to ischemia for 60 min,followed by 90 min ofreperfusion with or without BV treatment.Results：Lungs in the I/R group exhibited significant decrease in tidal volume （1.44 ± 0.23 ml/min in I/R group vs.2.41 ± 0.31 ml/min in sham group;P 〈 0.001）,lung compliance （0.27 ± 0.06 ml/cmH2O in I/R group vs.0.44 ± 0.09 ml/cmH2O in sham group;P 〈 0.001;1 cmH2O=0.098 kPa）,and oxygen partial pressure （PaO2） levels （64.12 ± 12 mmHg in FR group vs.114 ± 8.0 mmHg in sham group;P 〈 0.001;1 mmHg =0.133 kPa）.In contrast,these parameters in the BV group （2.27 ± 0.37 ml/min of tidal volume,0.41 ± 0.10 ml/ cmH2O of compliance,and 98.7 ± 9.7 mmHg of PaO2） were significantly higher compared with the I/R group （P =0.004,P 〈 0.001,and P 〈 0.001,respectively）.Compared to the I/R group,the contents of superoxide dismutase were significantly higher （47.07 ± 7.91 U/mg protein vs.33.84 ± 10.15 U/mg protein;P =0.005） while the wet/dry weight ratio （P 〈 0.01）,methane dicarboxylic aldehyde （1.92 ± 0.25 nmol/mg protein vs.2.67 ± 0.46 nmol/mg protein;P 〈 0.001）,and adenosine triphosphate contents （297.05 ± 47.45 nmol/mg protein vs.208.09 ± 29.11 nmol/mg protein;P =0.005） were markedly lower in BV-treated lungs.Histological analysis revealed that BV alleviated LIRI.Furthermore,the expression of inflammatory cytokines （interleukin-1 β,interleukin-6,and tumor necrosis factor-α） was downregulated and the expression of cyclooxygenase-2,inducible nitric oxide synthase,and Jun N-terminal kinase was significantly reduced in BV group （all P 〈 0.01 compared to I/R group）.Finally,the apoptosis index in the BV group was significantly decreased （P 〈 0.01 compared to I/R group）.Conclusion：BV protects lung IRI through its antioxidative,anti-inflammatory,and anti-apoptotic effects.
