Background Increasing evidences indicate that an activated renin-angiotensin system （RAS） causes an imbalance between the vasoconstrictive and vasodilator mechanisms involving the pulmonary circulation leading to th...Background Increasing evidences indicate that an activated renin-angiotensin system （RAS） causes an imbalance between the vasoconstrictive and vasodilator mechanisms involving the pulmonary circulation leading to the development of pulmonary arterial hypertension （PAH）. Angiotensin-converting enzyme 2 （ACE2）, a primary component of the vasoprotective axis in RAS, is recently identified that it has regulatory actions in lung pathophysiology, but the mechanism in these processes is uncertain yet. Methods Severe PAH was induced by monocrotaline injection one week following pneumonectomy in rats. The activation of ACE2 by continuous injection of resorcinolnaphthalein was studied by real time-polymerase chain reaction （RT-PCR）, Western blotting and fluorogenic peptide assay. Endothelial functions were evaluated by the response to acetylcholine and cytokines were measured by RT-PCR seven days after monocrotaline injection. The PAH-related hemodynamics and pathological changes were examined at day 21 when severe PAH was completely established. Results Resorcinolnaphthalein caused significant activation of ACE2 in both normal and diseased rats in 7 days after treatment. The pulmonary arterial pressure （PAP） started to increase at least 7 days after monocrotaline injection, and the rats developed severe PAH in 21 days with high PAP, right ventricular hypertrophy and neointimal formation. Treatment with resorcinolnaphthalein prevented these features. Resorcinolnaphthalein caused an improved endothelia-dependent vasorelaxation and decrease in proinflammatory cytokines （tumor necrosis factor （TNF）-a, monocyte chemoattractant protein-1 （MCP-1）, interleukin （IL）-6） and increase in anti-inflammatory cytokine IL-10 in the early stage of the pathogenesis. Conclusions These results demonstrated that activation of ACE2 by continuous injection of resorcinolnaphthalein prevented the development of PAH through improving early endothelial dysfunction and mediating the level of proinflammatory and anti-inflammatory cytokines.展开更多
Background Young children are susceptible to pulmonary injury, and acute lung injury （ALl） often results in a high mortality and financial costs in pediatric patients. A good ALl model will help us to gain a better ...Background Young children are susceptible to pulmonary injury, and acute lung injury （ALl） often results in a high mortality and financial costs in pediatric patients. A good ALl model will help us to gain a better understanding of the real pathophysiological picture and to evaluate novel treatment approaches to acute respiratory distress syndrome （ARDS） more accurately and liberally. This study aimed to establish a hemodynamically stable and reproducible model with ALl in piglet induced by oleic acid. Methods Six Chinese mini-piglets were used to establish ALl models by oleic acid. Hemodynamic and pulmonary function data were measured. Histopathological assessment was performed. Results Mean blood pressure, heart rate （HR）, cardiac output （CO）, central venous pressure （CVP） and left atrial pressure （LAP） were sharply decreased after oleic acid given, while the mean pulmonary arterial pressure （MPAP） was increased in comparison with baseline （P 〈0.05）. pH, arterial partial pressure of 02 （PaO2）, PaO2/inspired 02 fraction （FiO2） and lung compliance decreased, while PaCO2 and airway pressure increased in comparison with baseline （P 〈0.05）. The lung histology showed severe inflammation, hyaline membranes, intra-alveolar and interstitial hemorrhage. Conclusion This experiment established a stable model which allows for a diversity of studies on early lung injury.展开更多
Background An inflammatory response leading to organ dysfunction and failure continues to be a major problem after injury in many clinical conditions such as sepsis, severe burns, and trauma. It is increasingly recogn...Background An inflammatory response leading to organ dysfunction and failure continues to be a major problem after injury in many clinical conditions such as sepsis, severe burns, and trauma. It is increasingly recognized that atrial natriuretic peptide （ANP） possesses a broad range of biological activities, including effects on endothelial function and inflammation. A recent study has revealed that ANP exerts anti-inflammatory effects. In this study we tested the effects of human ANP （hANP） on lung injury in a model of oleic acid （OA）-induced acute lung injury （ALl） in rats. Methods Rats were randomly assigned to three groups （n=6 in each group）. Rats in the control group received a 0.9% solution of NaCI （1 ml-kg-l.h1） by continuous intravenous infusion, after 30 minutes a 0.9% solution of NaCI （1 ml/kg） was injected intravenously, and then the 0.9% NaCI infusion was restarted. Rats in the ALl group received a 0.9% NaCI solution （1 ml-kgl-h-~） intravenous infusion, after 30 minutes OA was injected intravenously （0.1 ml/kg）, and then the 0.9% NaCI infusion was restarted. Rats in the hANP-treated ALl group received a hANP （0.1 IJg.kg-Lmin~） infusion, after 30 minutes OA was injected intravenously （0.1 ml/kg）, and then the hANP infusion was restarted. The anti-inflammation effects of hANP were evaluated by histological examination and determination of serum cytokine levels. Results Serum interleukin （IL）-113, IL-6, IL-10 and tumor necrosis factor （TNF） a were increased in the ALl group at six hours. The levels of all factors were significantly lower in the hANP treated rats （P 〈0.005）. Similarly, levels of IL-113, IL-6, IL-10 and TNF-a were higher in the lung tissue in the ALl group at six hours, hANP treatment significantly reduced the levels of these factors in the lungs （P 〈0.005）. Histological examination revealed marked reduction in interstitial congestion, edema, and inflammation. Conclusion hANP can attenuate inflammation in OA-induced lung injury in rat model.展开更多
Background Pulmonary artery perfusion during cardiopulmonary bypass （CPB） is a novel adjunctive method, which can minimize the lung ischemic-reperfusion injury and inflammatory response. This study evaluated the pro...Background Pulmonary artery perfusion during cardiopulmonary bypass （CPB） is a novel adjunctive method, which can minimize the lung ischemic-reperfusion injury and inflammatory response. This study evaluated the protective effect of pulmonary perfusion with hypothermic HTK solution in corrections of congenital heart defects with pulmonary hypertension. Methods Between June 2009 and December 2009, 24 consecutive infants with congenital heart defects and pulmonary hypertension were randomly divided into perfused group （n=12） and control group （n=-12）. Oxygen index, alveolar-arterial 02 gradient, serum levels of malondialchehyche （MDA）, interleukin （IL）-6, -8, -10, soluble intercellular adhesion molecule-1 （slCAM-1）, and P-seiectin were measured before commencement and serially for 48 hours after termination of bypass. Results Oxygenation values were better preserved in the perfused group than in the control group. The serum levels of IL-6 increased immediately after CPB in both groups and returned to baseline at 48 hours after CPB, but it was restored faster and earlier in the perfused group. The serum levels of IL-8, slCAMol, and MDA remained at baseline at each point after CPB in the perfused group and elevated significantly immediately after CPB in the control group, except for slCAM-1 The serum level of IL-10 increased immediately after CPB and decreased to baseline at 48 hours after CPB in both groups, but the IL-10 level in the perfused group was significantly higher than in the control group at 12 hours after CPB. The serum P-selectin levels in the control group immediately after CPB were significantly higher than prebypass levels. Moreover, there were no significant differences in postoperative clinical characters, except for the intubated time. Conclusion In infants with congenital heart defects, pulmonary perfusion with hypothermic HTK solution during cardiopulmonary bypass could ameliorate lung function and reduce the inflammatory response.展开更多
Background Pediatric patients are susceptible to lung injury.Acute lung injury in children often results in high mortality.Partial liquid ventilation （PLV） has been shown to markedly improve oxygenation and reduce h...Background Pediatric patients are susceptible to lung injury.Acute lung injury in children often results in high mortality.Partial liquid ventilation （PLV） has been shown to markedly improve oxygenation and reduce histologic evidence of injury in a number of lung injury models.This study was designed to examine the hypothesis that PLV would attenuate the production of local and systemic tumor necrosis factor （TNF）-α in an immature piglet model of acute lung injury induced by oleic acid （OA）.Methods Twelve Chinese immature piglets were induced acute lung injury by OA.The animals were randomly assigned to two groups of six animals,（1） conventional mechanical ventilation （MV） group and （2） PLV with 10 ml/kg FC-77 group.Results Compared with MV group,the PLV group had better cardiopulmonary variables （P 〈0.05）.These variables included heart rate,mean blood pressure,blood pH,partial pressure of arterial oxygen （PaO2）,PaO2/inspired O2 fraction （FiO2） and partial pressure of arterial carbon dioxide （PaCO2）.PLV reduced TNF-α levels both in plasma and tissue compared with MV group （P 〈0.05）.Conclusion PLV provides protective effects against TNF-a response in OA-induced acute lung injury in immature piglets.展开更多
Background Animal models that demonstrate changes of renal function in response to acute lung injury （ALl） and mechanical ventilation （MV） are few. The present study was performed to examine the effect of ALl indu...Background Animal models that demonstrate changes of renal function in response to acute lung injury （ALl） and mechanical ventilation （MV） are few. The present study was performed to examine the effect of ALl induced by oleic acid （OA） in combination with conventional MV strategy on renal function in piglets. Methods Twelve Chinese mini-piglets were randomly divided into two groups： the OA group （n=6）, animals were ventilated with a conventional MV strategy of 12 ml/kg and suffered an ALl induced by administration of OA, and the control group （n=6）, animals were ventilated with a protective MV strategy of 6 ml/kg and received the same amount of stedle saline. Results Six hours after OA injection a severe lung injury and a mild-moderate degree of renal histopathological injury were seen, while no apparent histological abnormalities were observed in the control group. Although we observed an increase in the plasma concentrations of creatinine and urea after ALl, there was no significant difference compared with the control group. Plasma concentrations of neutrophil gelatinase-associated lipocalin （NGAL） and cystatin C increased （5.6＋1.3） and （7.4＋1.5） times in the OA group compared to baseline values, and were significantly higher than the values in the control group. OA injection in combination with conventional MV strategy resulted in a dramatic aggravation of hemodynamic and blood gas exchange parameters, while these parameters remained stable during the experiment in the control group. The plasma expression of TNF-a and IL-6 in the OA group were significantly higher than that in the control group. Compared with high expression in the lung and renal tissue in the OA group, TNF-a and IL-6 were too low to be detected in the lung and renal tissue in the control group. Conclusions OA injection in combination with conventional MV strategy not only resulted in a severe lung injury but also an apparent renal injury. The potential mechanisms involved a cytokine response of TNF-a and IL-6 in plasma, lung and renal tissues.展开更多
Background Pediatric patients are susceptible to lung injury that does not respond to traditional therapies. Total liquid ventilation has been developed as an alternative ventilatory strategy for severe lung injury. T...Background Pediatric patients are susceptible to lung injury that does not respond to traditional therapies. Total liquid ventilation has been developed as an alternative ventilatory strategy for severe lung injury. The aim of this study is to investigate the effect of total liquid ventilation on oleic acid （OA）-induced lung injury in piglets. Methods Twelve Chinese immature piglets were induced acute lung injury by OA. Twelve piglets were randomly treated with conventional gas ventilation （control group） or total liquid ventilation （study group） for 240 minutes. Samples for blood gas analysis were collected before, and at 60-minute intervals after OA-induced lung injury. The degree of lung injury was quantified by histologic examination. The inflammatory cells and the levels of IL-1β, IL-6, IL-10 and TNF-α in plasma, tissue and bronchoalveolar lavage were analyzed. Results Neutrophil and macrophage counts in bronchoalveolar lavage were significantly decreased in the study group （P〈0.05）. The total lung injury score was also reduced in the study group （P〈0.05）. The concentrations of IL-1β, IL-6, IL-10 and TNF-α in plasma, tissue and bronchoalveolar lavage were significantly reduced in the study group （P〈0.05）. Conclusions Total liquid ventilation reduces biochemical and histoloaic OA-induced luna iniurv in nialets.展开更多
Background Cyanotic congenital heart defects with decreased pulmonary blood flow due to lung ischemia,hypoxia,and others lead to infant morbidity and mortality more than acyanotic heart disease does.Despite the great ...Background Cyanotic congenital heart defects with decreased pulmonary blood flow due to lung ischemia,hypoxia,and others lead to infant morbidity and mortality more than acyanotic heart disease does.Despite the great effort of medical research,their genetic link and underlying microRNAs molecular mechanisms remain obscure.In this study,we aimed to investigate microRNAs regulation during cyanotic defects in lung of immature piglets.Methods Cyanotic piglet model was induced by main pulmonary artery-left atrium shunt with distal pulmonary artery banding.Four weeks later,hemodynamic parameters confirmed the development of cyanotic defects and pulmonary lobe RNA was extracted from all animals.We studied the repertoire of porcine lung microRNAs by Solexa deep sequencing technology and quantified highly expressed microRNAs by microarray hybridization.Furthermore,we quantitated selected microRNAs from cyanotic and control piglets by quantitative RT-PCR.Results After surgical procedure 4 weeks later,the cyanotic model produced lower arterial oxygen tension,arterial oxygen saturation,and higher arterial carbon dioxide tension,hematocrit and hemoglobin concentration than controls （all P 〈0.05）.In 1273 miRNAs expressed in the immature piglets lungs,2 most abundant microRNAs （miR-370 and miR-320） demonstrated significant difference between cyanotic and control group （all P 〈0.05）.Conclusion Our results extended lung microRNA profile in immature piglets and suggested that miR-370 and miR-320 are significantly up-regulated in cyanotic lung tissues.展开更多
基金This study was supported by grants from the National Natural Science Foundation of China （No. 30972958）, the Natural Science Foundation of Beijing （No. 7112046） and the Capital Characteristics Clinical Application Project （No. Z101107050210020）
文摘Background Increasing evidences indicate that an activated renin-angiotensin system （RAS） causes an imbalance between the vasoconstrictive and vasodilator mechanisms involving the pulmonary circulation leading to the development of pulmonary arterial hypertension （PAH）. Angiotensin-converting enzyme 2 （ACE2）, a primary component of the vasoprotective axis in RAS, is recently identified that it has regulatory actions in lung pathophysiology, but the mechanism in these processes is uncertain yet. Methods Severe PAH was induced by monocrotaline injection one week following pneumonectomy in rats. The activation of ACE2 by continuous injection of resorcinolnaphthalein was studied by real time-polymerase chain reaction （RT-PCR）, Western blotting and fluorogenic peptide assay. Endothelial functions were evaluated by the response to acetylcholine and cytokines were measured by RT-PCR seven days after monocrotaline injection. The PAH-related hemodynamics and pathological changes were examined at day 21 when severe PAH was completely established. Results Resorcinolnaphthalein caused significant activation of ACE2 in both normal and diseased rats in 7 days after treatment. The pulmonary arterial pressure （PAP） started to increase at least 7 days after monocrotaline injection, and the rats developed severe PAH in 21 days with high PAP, right ventricular hypertrophy and neointimal formation. Treatment with resorcinolnaphthalein prevented these features. Resorcinolnaphthalein caused an improved endothelia-dependent vasorelaxation and decrease in proinflammatory cytokines （tumor necrosis factor （TNF）-a, monocyte chemoattractant protein-1 （MCP-1）, interleukin （IL）-6） and increase in anti-inflammatory cytokine IL-10 in the early stage of the pathogenesis. Conclusions These results demonstrated that activation of ACE2 by continuous injection of resorcinolnaphthalein prevented the development of PAH through improving early endothelial dysfunction and mediating the level of proinflammatory and anti-inflammatory cytokines.
基金This study was supported-by grants from the National Natural Science Foundation of China （No. 30670928, No. 81070055） and the Beijing Municipal Education Commission （No. PXM2011_014226_07 000060, Z11110006150000）.
文摘Background Young children are susceptible to pulmonary injury, and acute lung injury （ALl） often results in a high mortality and financial costs in pediatric patients. A good ALl model will help us to gain a better understanding of the real pathophysiological picture and to evaluate novel treatment approaches to acute respiratory distress syndrome （ARDS） more accurately and liberally. This study aimed to establish a hemodynamically stable and reproducible model with ALl in piglet induced by oleic acid. Methods Six Chinese mini-piglets were used to establish ALl models by oleic acid. Hemodynamic and pulmonary function data were measured. Histopathological assessment was performed. Results Mean blood pressure, heart rate （HR）, cardiac output （CO）, central venous pressure （CVP） and left atrial pressure （LAP） were sharply decreased after oleic acid given, while the mean pulmonary arterial pressure （MPAP） was increased in comparison with baseline （P 〈0.05）. pH, arterial partial pressure of 02 （PaO2）, PaO2/inspired 02 fraction （FiO2） and lung compliance decreased, while PaCO2 and airway pressure increased in comparison with baseline （P 〈0.05）. The lung histology showed severe inflammation, hyaline membranes, intra-alveolar and interstitial hemorrhage. Conclusion This experiment established a stable model which allows for a diversity of studies on early lung injury.
基金This study was supported by grants from the National Natural Science Foundation of China （No. 30670928, No. 81070055）, Beijing Educational Commission （No. PXM2011_014226 07 000060）, Beijing Science and Technology Commission （No. Z111100074911001）, Beijing Natural Science Foundation （No. 7112046, No. 7122056）, Beijing Health System High Level Health Technical Personnel Training Plan （No. 2011-1-4）.
文摘Background An inflammatory response leading to organ dysfunction and failure continues to be a major problem after injury in many clinical conditions such as sepsis, severe burns, and trauma. It is increasingly recognized that atrial natriuretic peptide （ANP） possesses a broad range of biological activities, including effects on endothelial function and inflammation. A recent study has revealed that ANP exerts anti-inflammatory effects. In this study we tested the effects of human ANP （hANP） on lung injury in a model of oleic acid （OA）-induced acute lung injury （ALl） in rats. Methods Rats were randomly assigned to three groups （n=6 in each group）. Rats in the control group received a 0.9% solution of NaCI （1 ml-kg-l.h1） by continuous intravenous infusion, after 30 minutes a 0.9% solution of NaCI （1 ml/kg） was injected intravenously, and then the 0.9% NaCI infusion was restarted. Rats in the ALl group received a 0.9% NaCI solution （1 ml-kgl-h-~） intravenous infusion, after 30 minutes OA was injected intravenously （0.1 ml/kg）, and then the 0.9% NaCI infusion was restarted. Rats in the hANP-treated ALl group received a hANP （0.1 IJg.kg-Lmin~） infusion, after 30 minutes OA was injected intravenously （0.1 ml/kg）, and then the hANP infusion was restarted. The anti-inflammation effects of hANP were evaluated by histological examination and determination of serum cytokine levels. Results Serum interleukin （IL）-113, IL-6, IL-10 and tumor necrosis factor （TNF） a were increased in the ALl group at six hours. The levels of all factors were significantly lower in the hANP treated rats （P 〈0.005）. Similarly, levels of IL-113, IL-6, IL-10 and TNF-a were higher in the lung tissue in the ALl group at six hours, hANP treatment significantly reduced the levels of these factors in the lungs （P 〈0.005）. Histological examination revealed marked reduction in interstitial congestion, edema, and inflammation. Conclusion hANP can attenuate inflammation in OA-induced lung injury in rat model.
文摘Background Pulmonary artery perfusion during cardiopulmonary bypass （CPB） is a novel adjunctive method, which can minimize the lung ischemic-reperfusion injury and inflammatory response. This study evaluated the protective effect of pulmonary perfusion with hypothermic HTK solution in corrections of congenital heart defects with pulmonary hypertension. Methods Between June 2009 and December 2009, 24 consecutive infants with congenital heart defects and pulmonary hypertension were randomly divided into perfused group （n=12） and control group （n=-12）. Oxygen index, alveolar-arterial 02 gradient, serum levels of malondialchehyche （MDA）, interleukin （IL）-6, -8, -10, soluble intercellular adhesion molecule-1 （slCAM-1）, and P-seiectin were measured before commencement and serially for 48 hours after termination of bypass. Results Oxygenation values were better preserved in the perfused group than in the control group. The serum levels of IL-6 increased immediately after CPB in both groups and returned to baseline at 48 hours after CPB, but it was restored faster and earlier in the perfused group. The serum levels of IL-8, slCAMol, and MDA remained at baseline at each point after CPB in the perfused group and elevated significantly immediately after CPB in the control group, except for slCAM-1 The serum level of IL-10 increased immediately after CPB and decreased to baseline at 48 hours after CPB in both groups, but the IL-10 level in the perfused group was significantly higher than in the control group at 12 hours after CPB. The serum P-selectin levels in the control group immediately after CPB were significantly higher than prebypass levels. Moreover, there were no significant differences in postoperative clinical characters, except for the intubated time. Conclusion In infants with congenital heart defects, pulmonary perfusion with hypothermic HTK solution during cardiopulmonary bypass could ameliorate lung function and reduce the inflammatory response.
基金This study was supported by the grants from National Natural Science Foundation of China （No. 30670928 and No. 81070055）, Beijing Municipal Education Commission （No. PXM2011_014226 07 000060）, Beijing Municipal Science Committee （No. Z11110006150000） and Beijing Natural Science Foundation （No. 7122056）.We are grateful to Dr. LING Feng, Dr. LIU Ai-jun, Dr. LI Gang and Dr. XU Yu-lin for their preparation of the animals, to Dr. LIU Yang-qing and Dr. LIU De-bin for their histopathological assessment.
文摘Background Pediatric patients are susceptible to lung injury.Acute lung injury in children often results in high mortality.Partial liquid ventilation （PLV） has been shown to markedly improve oxygenation and reduce histologic evidence of injury in a number of lung injury models.This study was designed to examine the hypothesis that PLV would attenuate the production of local and systemic tumor necrosis factor （TNF）-α in an immature piglet model of acute lung injury induced by oleic acid （OA）.Methods Twelve Chinese immature piglets were induced acute lung injury by OA.The animals were randomly assigned to two groups of six animals,（1） conventional mechanical ventilation （MV） group and （2） PLV with 10 ml/kg FC-77 group.Results Compared with MV group,the PLV group had better cardiopulmonary variables （P 〈0.05）.These variables included heart rate,mean blood pressure,blood pH,partial pressure of arterial oxygen （PaO2）,PaO2/inspired O2 fraction （FiO2） and partial pressure of arterial carbon dioxide （PaCO2）.PLV reduced TNF-α levels both in plasma and tissue compared with MV group （P 〈0.05）.Conclusion PLV provides protective effects against TNF-a response in OA-induced acute lung injury in immature piglets.
文摘Background Animal models that demonstrate changes of renal function in response to acute lung injury （ALl） and mechanical ventilation （MV） are few. The present study was performed to examine the effect of ALl induced by oleic acid （OA） in combination with conventional MV strategy on renal function in piglets. Methods Twelve Chinese mini-piglets were randomly divided into two groups： the OA group （n=6）, animals were ventilated with a conventional MV strategy of 12 ml/kg and suffered an ALl induced by administration of OA, and the control group （n=6）, animals were ventilated with a protective MV strategy of 6 ml/kg and received the same amount of stedle saline. Results Six hours after OA injection a severe lung injury and a mild-moderate degree of renal histopathological injury were seen, while no apparent histological abnormalities were observed in the control group. Although we observed an increase in the plasma concentrations of creatinine and urea after ALl, there was no significant difference compared with the control group. Plasma concentrations of neutrophil gelatinase-associated lipocalin （NGAL） and cystatin C increased （5.6＋1.3） and （7.4＋1.5） times in the OA group compared to baseline values, and were significantly higher than the values in the control group. OA injection in combination with conventional MV strategy resulted in a dramatic aggravation of hemodynamic and blood gas exchange parameters, while these parameters remained stable during the experiment in the control group. The plasma expression of TNF-a and IL-6 in the OA group were significantly higher than that in the control group. Compared with high expression in the lung and renal tissue in the OA group, TNF-a and IL-6 were too low to be detected in the lung and renal tissue in the control group. Conclusions OA injection in combination with conventional MV strategy not only resulted in a severe lung injury but also an apparent renal injury. The potential mechanisms involved a cytokine response of TNF-a and IL-6 in plasma, lung and renal tissues.
基金This study was supported by grants from the National Natural Science Foundation of China （No. 81070055）, Beijing Science and Technology Commission （No. ZI 11100074911001 ）, Beijing Natural Science Foundation （No. 7112046, No. 7122056）, Beijing Health System High Level Health Technical Personnel Training Plan （No. 2011-1-4）, and Basic and Clinical Cooperation Project of Capital Medical University （No. 13JL26）.
文摘Background Pediatric patients are susceptible to lung injury that does not respond to traditional therapies. Total liquid ventilation has been developed as an alternative ventilatory strategy for severe lung injury. The aim of this study is to investigate the effect of total liquid ventilation on oleic acid （OA）-induced lung injury in piglets. Methods Twelve Chinese immature piglets were induced acute lung injury by OA. Twelve piglets were randomly treated with conventional gas ventilation （control group） or total liquid ventilation （study group） for 240 minutes. Samples for blood gas analysis were collected before, and at 60-minute intervals after OA-induced lung injury. The degree of lung injury was quantified by histologic examination. The inflammatory cells and the levels of IL-1β, IL-6, IL-10 and TNF-α in plasma, tissue and bronchoalveolar lavage were analyzed. Results Neutrophil and macrophage counts in bronchoalveolar lavage were significantly decreased in the study group （P〈0.05）. The total lung injury score was also reduced in the study group （P〈0.05）. The concentrations of IL-1β, IL-6, IL-10 and TNF-α in plasma, tissue and bronchoalveolar lavage were significantly reduced in the study group （P〈0.05）. Conclusions Total liquid ventilation reduces biochemical and histoloaic OA-induced luna iniurv in nialets.
基金This study was supported by grants from the National Natural Science Foundation of China （No. 81100116）, the Beijing Natural Science Foundation （No. 7112046）, and Capital Citizens＇ Health Project Cultivation of Beijing Municipal Science and Technology Commissions （No. Z 111100074911001）.Acknowledgments： The authors are grateful to Dr. LI Gang and Dr. XU Yu-lin for the animal experiment＇s assistance, and ZHANG Yanbin and ZHANG Shao-bin for their bioinformatics assistance.
文摘Background Cyanotic congenital heart defects with decreased pulmonary blood flow due to lung ischemia,hypoxia,and others lead to infant morbidity and mortality more than acyanotic heart disease does.Despite the great effort of medical research,their genetic link and underlying microRNAs molecular mechanisms remain obscure.In this study,we aimed to investigate microRNAs regulation during cyanotic defects in lung of immature piglets.Methods Cyanotic piglet model was induced by main pulmonary artery-left atrium shunt with distal pulmonary artery banding.Four weeks later,hemodynamic parameters confirmed the development of cyanotic defects and pulmonary lobe RNA was extracted from all animals.We studied the repertoire of porcine lung microRNAs by Solexa deep sequencing technology and quantified highly expressed microRNAs by microarray hybridization.Furthermore,we quantitated selected microRNAs from cyanotic and control piglets by quantitative RT-PCR.Results After surgical procedure 4 weeks later,the cyanotic model produced lower arterial oxygen tension,arterial oxygen saturation,and higher arterial carbon dioxide tension,hematocrit and hemoglobin concentration than controls （all P 〈0.05）.In 1273 miRNAs expressed in the immature piglets lungs,2 most abundant microRNAs （miR-370 and miR-320） demonstrated significant difference between cyanotic and control group （all P 〈0.05）.Conclusion Our results extended lung microRNA profile in immature piglets and suggested that miR-370 and miR-320 are significantly up-regulated in cyanotic lung tissues.
