Model Of Acid-induced Acute Lung Injury Research Articles

Keratinocyte Growth Factor-2 Is Protective in Oleic Acid-Induced Acute Lung Injury in Rats.

Objective The aim of this study was to examine the role of keratinocyte growth factor-2 (KGF-2) in oleic acid-induced acute lung injury (ALI) in rats. Methods Forty-five healthy adult male Sprague Dawley rats were divided into 3 groups. Rat ALI model was established by injection of 0.01 mL/kg oleic acid into the tail vein. Rats in the control group were injected with the same amount of normal saline (NS). In the ALI + KGF-2 group, 5 mg/kg of KGF-2 was instilled into the airway of rats 72 hours before the model preparation, and the control group and the ALI model group were instilled with the same amount of NS. The lung permeability index (LPI) and lung wet/dry weight (W / D) ratios were measured 8 hours after the model preparation. The permeability of pulmonary microvascular endothelium was evaluated by Evans blue leakage test. Histopathological changes were observed under light microscope and the ALI pathology score (LIS) was calculated. Ultrastructural changes of lung tissue were observed under electron microscope. The apoptosis was detected by TUNEL assay. The expression of Claudin-5, ZO-1, and VE Cadherin in lung tissue was qualitatively and quantitatively analyzed by immunohistochemistry, Western Blot, and qRT-PCR, respectively. Results The ALI model group had severe lung injury and obvious pathological changes, including alveolar septal thickening and inflammatory cell infiltration. TUNEL assay showed that the apoptosis of ALI group was significantly increased. The LIS score, lung W/D ratio, LPI, and Evans blue leakage were significantly higher than those in the control group; electron microscopy showed that the alveolar-capillary barrier was severely damaged in the ALI group. Compared with the control group, the expression of Claudin-5, ZO-1, and VE cadherin in the lung tissue of the ALI model group was significantly attenuated. After pretreatment with KGF-2, the degree of lung tissue damage was significantly reduced and the pathological changes were significantly improved. TUNEL assay showed that the apoptosis of ALI group was decreased. Lung W/D ratio, LPI, and Evans blue leakage decreased; electron microscopy showed that the alveolar-capillary barrier of ALI group recovered significantly. Compared with the ALI model group, the expression of Claudin-5, ZO-1, and VE cadherin in the lung tissue of the KGF-2 pretreatment group increased. Conclusion The results indicate that KGF-2 may attenuate oleic acid-induced ALI in rats by maintaining the pulmonary microvascular endothelial barrier, which is an effective ALI preventive measure.

Atrial natriuretic peptide attenuates inflammatory responses on oleic acid-induced acute lung injury model in rats

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 (ALI) 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 NaCl (1 ml·kg-1·h-1) by continuous intravenous infusion, after 30 minutes a 0.9% solution of NaCl (1 ml/kg) was injected intravenously, and then the 0.9% NaCl infusion was restarted. Rats in the ALI group received a 0.9% NaCl solution (1 ml·kg-1·h-1) intravenous infusion, after 30 minutes OA was injected intravenously (0.1 ml/kg), and then the 0.9% NaCl infusion was restarted. Rats in the hANP-treated ALI group received a hANP (0.1 μg·kg-1·min-1) 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)-1β, IL-6, IL-10 and tumor necrosis factor (TNF) α were increased in the ALI group at six hours. The levels of all factors were significantly lower in the hANP treated rats (P <0.005). Similarly, levels of IL-1β, IL-6, IL-10 and TNF-α were higher in the lung tissue in the ALI 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 an OA-induced lung injury in rat model.

Eliminating or blocking 12/15-lipoxygenase reduces neutrophil recruitment in mouse models of acute lung injury

IntroductionAcute lung injury (ALI) is a common disease in critically ill patients with a high morbidity and mortality. 12/15-lipoxygenase (12/15-LO) is an enzyme generating 12-hydroxy-eicosatetraenoic acid (12-HETE) and 15-HETE from arachidonic acid. It has been shown that 12/15-LO is involved in the regulation of vascular permeability during ALI.MethodsTo test whether 12/15-LO participates in leukocyte recruitment into the lung, we investigated the role of 12/15-LO in mouse models of lipopolysaccharide (LPS)-induced pulmonary inflammation and acid-induced ALI, a clinically relevant model of acute lung injury.ResultsThe increase in neutrophil recruitment following LPS inhalation was reduced in 12/15-LO-deficient (Alox15-/-) mice and in wild-type (WT) mice after the blocking of 12/15-LO with a pharmacological inhibitor. Bone marrow chimeras revealed that 12/15-LO in hematopoietic cells regulates neutrophil accumulation in the interstitial and alveolar compartments, whereas the accumulation of neutrophils in the intravascular compartment is regulated by 12/15-LO in non-hematopoietic and hematopoietic cells. Mechanistically, the increased plasma levels of the chemokine CXCL1 in Alox15-/- mice led to a reduced response of the neutrophil chemokine receptor CXCR2 to stimulation with CXCL1, which in turn abrogated neutrophil recruitment. Alox15-/- mice also showed decreased edema formation, reduced neutrophil recruitment and improved gas exchange in an acid-induced ALI model.ConclusionsOur findings suggest that 12/15-LO modulates neutrophil recruitment into the lung by regulating chemokine/chemokine receptor homeostasis.

Improved survival and reduced vascular permeability by eliminating or blocking 12/15-lipoxygenase in mouse models of acute lung injury (ALI).

Acute lung injury (ALI) is a prevalent disease associated with high mortality. 12/15-lipoxygenase (12/15-LO) is an enzyme producing 12-hydroxyeicosatetraenoic acid (HETE) and 15-HETE from arachidonic acid. To test whether 12/15-LO is involved in increasing vascular permeability in the lung, we investigated the role of 12/15-LO in murine models of LPS-induced pulmonary inflammation and clinically relevant acid-induced ALI. The vascular permeability increase upon LPS inhalation was abolished in Alox15(-/-) mice lacking 12/15-LO and in wild-type mice after pharmacological blockade of 12/15-LO. Alox15(-/-) mice also showed improved gas exchange, reduced permeability increase, and prolonged survival in the acid-induced ALI model. Bone marrow chimeras and reconstitution experiments revealed that 12-HETE produced by hematopoietic cells regulates vascular permeability through a CXCR2-dependent mechanism. Our findings suggest that 12/15-LO-derived 12-HETE is a key mediator of vascular permeability in acute lung injury.

Estabilidade do modelo animal de lesão pulmonar aguda induzida por ácido oleico

To evaluate the stability of hemodynamic, respiratory and gas exchange variables in an animal model of oleic acid-induced acute lung injury. This was an experimental study involving 10 mongrel dogs. The variables were measured at baseline, as well as at 30, 60, 90 and 120 min after the administration of oleic acid. In order to analyze repeated measurements, linear and quadratic effects were tested. Mixed linear models with diversified variance and covariance structures were used, depending on the variable studied. We found that mean arterial blood pressure stabilized at 30 min, as did heart rate, pulmonary arterial pressure and pulmonary capillary pressure at 60 min. Respiratory rate, tidal volume, minute volume and respiratory work stabilized at 30 min. Regarding gas exchange variables, PaO2, PaO2/FiO2 ratio and pulmonary shunt fraction stabilized at 30 min. The remaining variables maintained a continuous rise or fall. This oleic acid-induced acute lung injury model is stable for some of the variables tested, although stabilization occurs at different times. The respiratory and gas exchange variables stabilized at 30 min, whereas the hemodynamic variables stabilized at 60 min.