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 gr...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.展开更多
Background It has found that ischemic postconditioning （IPO） might decrease pulmonary ischemia/reperfusion （I/ R） injury,which is one of the main reasons of lung injury caused by cardiopulmonary bypass （CPB）.It ...Background It has found that ischemic postconditioning （IPO） might decrease pulmonary ischemia/reperfusion （I/ R） injury,which is one of the main reasons of lung injury caused by cardiopulmonary bypass （CPB）.It was found that aquaporins （AQPs） play a role in the maintenance of fluid homeostasis.But it is still unclear whether IPO influences the expression of aquaporin-1 （AQP1）.This study was designed to investigate whether IPO can reduce CPB-related lung injury and affect the expression of AQP1 of lungs.Methods Twelve healthy dogs were divided into control group （C group） and ischemia postconditioning group （IPO group）.CPB procedures were implemented.Ten minutes later,the left pulmonary artery was separated and blocked.Postconditioning consisted of two cycles of 5-minute pulmonary artery reperfusion/5-minute reocclusion starting at the beginning of reperfusion.The 2×4 cm tissues of both sides of pulmonary apex,superior,middle and inferior lobe were taken before CPB （T1）,before occlusion and reopening of left pulmonary artery （T2,T3）,and 2 hours after CPB （T4）.Samples were used to evaluate lung injury degrees and to detect the expression of AQP1.At T1 and T4,blood was collected from femoral artery to calculate pulmonary function.Results At T4,each pulmonary function showed significant deterioration compared with T1.Lung injury could be found at the onset of CPB.However,the expression of AQP1 decreased and wet to dry weight ratio （W/D） increased after T2.In the left lung of C group,the worst pulmonary function and structures were detected.The slightest changes were discovered in the right lung of C group.A close relationship between W/D and lung injury score was found.The lung injury score was negatively related with the expression of AQP1.It was found that the expression of AQP1 was negatively connected with W/D.Conclusions In dog CPB models,lung injury induced by CPB was related with down regulated expression of AQP1.AQP1 is believed to be involved in the mechanisms of展开更多
OBJECTIVE: To determine if aquaporin1 (AQP1) and aquaporin5 (AQP5) are expressed in the alveolar capillary membrane in rats. Moreover, to investigate the alteration of AQP1 and AQP5 in acute injured lungs. METHODS: Th...OBJECTIVE: To determine if aquaporin1 (AQP1) and aquaporin5 (AQP5) are expressed in the alveolar capillary membrane in rats. Moreover, to investigate the alteration of AQP1 and AQP5 in acute injured lungs. METHODS: The distribution of AQP1 and AQP5 in alveolar capillary membrane were investigated by immunohistochemistry and immunoelectron microscopy with affinity-purified antibodies to human AQP1 and AQP5. To study the possibility that alveolar capillary membrane AQP1 and AQP5 undergo altered regulation, we established a rat model using alveolar instillation of lipopolysaccharide (LPS). RESULTS: Immunolabelling showed AQP1 was stained primarily in the microvascular endotheli a of normal lungs, while AQP5 was expressed in type I pneumocytes. Immunohisto chemical analysis showed a significant decrease in the expression of AQP1 and AQP5 in injured lungs at 4h-48h after LPS instillation. AQP1 protein was resumed partly at 24h after LPS instillation and steroid administration, whereas AQP5 was unchanged. CONCLUSION: The decreased expressions of AQP1 and AQP5 in injured lungs suggest that both of them may play a role in abnormal fluid transportation.展开更多
基金supported by a grant from Technical Research and Development Fund of Shenzhen(No.JCYJ20140416122812032)
文摘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.
文摘Background It has found that ischemic postconditioning （IPO） might decrease pulmonary ischemia/reperfusion （I/ R） injury,which is one of the main reasons of lung injury caused by cardiopulmonary bypass （CPB）.It was found that aquaporins （AQPs） play a role in the maintenance of fluid homeostasis.But it is still unclear whether IPO influences the expression of aquaporin-1 （AQP1）.This study was designed to investigate whether IPO can reduce CPB-related lung injury and affect the expression of AQP1 of lungs.Methods Twelve healthy dogs were divided into control group （C group） and ischemia postconditioning group （IPO group）.CPB procedures were implemented.Ten minutes later,the left pulmonary artery was separated and blocked.Postconditioning consisted of two cycles of 5-minute pulmonary artery reperfusion/5-minute reocclusion starting at the beginning of reperfusion.The 2×4 cm tissues of both sides of pulmonary apex,superior,middle and inferior lobe were taken before CPB （T1）,before occlusion and reopening of left pulmonary artery （T2,T3）,and 2 hours after CPB （T4）.Samples were used to evaluate lung injury degrees and to detect the expression of AQP1.At T1 and T4,blood was collected from femoral artery to calculate pulmonary function.Results At T4,each pulmonary function showed significant deterioration compared with T1.Lung injury could be found at the onset of CPB.However,the expression of AQP1 decreased and wet to dry weight ratio （W/D） increased after T2.In the left lung of C group,the worst pulmonary function and structures were detected.The slightest changes were discovered in the right lung of C group.A close relationship between W/D and lung injury score was found.The lung injury score was negatively related with the expression of AQP1.It was found that the expression of AQP1 was negatively connected with W/D.Conclusions In dog CPB models,lung injury induced by CPB was related with down regulated expression of AQP1.AQP1 is believed to be involved in the mechanisms of
基金ThisprojectwassupportedbytheNationalNaturalScienceFoundationofChina (No 3 9870 3 3 8)
文摘OBJECTIVE: To determine if aquaporin1 (AQP1) and aquaporin5 (AQP5) are expressed in the alveolar capillary membrane in rats. Moreover, to investigate the alteration of AQP1 and AQP5 in acute injured lungs. METHODS: The distribution of AQP1 and AQP5 in alveolar capillary membrane were investigated by immunohistochemistry and immunoelectron microscopy with affinity-purified antibodies to human AQP1 and AQP5. To study the possibility that alveolar capillary membrane AQP1 and AQP5 undergo altered regulation, we established a rat model using alveolar instillation of lipopolysaccharide (LPS). RESULTS: Immunolabelling showed AQP1 was stained primarily in the microvascular endotheli a of normal lungs, while AQP5 was expressed in type I pneumocytes. Immunohisto chemical analysis showed a significant decrease in the expression of AQP1 and AQP5 in injured lungs at 4h-48h after LPS instillation. AQP1 protein was resumed partly at 24h after LPS instillation and steroid administration, whereas AQP5 was unchanged. CONCLUSION: The decreased expressions of AQP1 and AQP5 in injured lungs suggest that both of them may play a role in abnormal fluid transportation.
