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Objective To investigate the characteristics of pulmonary function and pathological changes in rats with acute lung injury (ALI) and provide experimental basis for further study on the mechanism of ALI.Methods Twenty five male SD rats were randomly divided into the control group (n =5) and acute lung injury (ALI) group (n =20).Lipopolysaccharide (LPS) (4.5 mg/kg) were injected into the ALI group rats to establish the ALI rat model.The rats in control group were given 150 μl isotonic saline.At 12,24,48,and 72 hours after injury,lung function of the rats were tested by Buxco small animal lung function test system,including the dynamic lung compliance (Cdyn),forced vital capacity (FVC),functional residual gas (FRC),quasi static compliance (Cchord),100th millisecond expiratory volume (FEV100),and airway resistance (RI).In addition,the bronchoalveolar lavage fluid (BALF) was collected for detection of protein level and tumor necrosis factor (TNF-alpha)concentration.At the same time,the changes of lung tissues were recorded,and the pathological changes were observed by HE staining.Results Compared with the control group,Cdyn,FVC,FRC,and FEV100 in ALI group were significantly decreased at each time point after injury (P ＜0.05 or ＜0.01),while the airway resistance (R1) in ALI group was significantly increased at 24 and 48 hours after injury (P ＜ 0.01).There was no significant difference in quasi static compliance (Cchord) between two groups (P ＞ 0.05).The protein level and TNF-alpha concentration of BALF in ALI group were increased significantly (P ＜0.05 or ＜0.01) 12-72 hours after injury (P ＜ 0.01).Compared with the control group,the whole lung was dark red in ALI group 12 hours after injury,and the most serious bleeding occurred in the pulmonary hilum area with single or multiple hemorrhagic foci of different sizes.Multiple punctate and focal bleeding of different sizes were seen on the lung surface,which were radially distributed around the pulmonary hilum.The color of lung tissue was gradually restored to normal at 72 hours after injury.Under the light microscope,pulmonary interstitial edema,inflammatory cell infiltration,pulmonary vascular congestion and focal pulmonary hemorrhage were observed 12 h after injury,showing typical ALl pathological changes.The pathological changes were the most significant at 24 hours and reduced obviously at 72 hours.Conclusions A single intratracheal injection of LPS can induce typical ALI pathological changes.There is a similar trend between the pulmonary function indexes,lung pathology characteristics,and the protein level of BALF and proinflammatory cytokine level,suggesting that the pulmonary function test parameters can provide reference for evaluation of ALI.
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Engraftment with ex-pulmonary adult stem cells has great potential for treatment of acute lung injury (ALI). The engrafted adult ex-pulmonary stem cells can migrate to the injured lung tissue guided by a series of signal factors released by injured pulmonary tissue cells. Stem cells localized in the injured lung tissue and inflammatory area can differentiate into lung tissue cells (including lung epithelial cells and pulmonary vascular endothelial cells) and exert their functions. The engrafted expulmonary adult stem cells are not only capable of differentiation, but also have anti-inflammatory effect and immunomodulatory effect, making the related area a focus of study.
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Objective: To investigate the effect of early dexamethasone treatment on seawater immersion-induced acute lung injury after open chest trauma. Methods: Twenty-four animals were evenly randomized into three groups: control group (CG), seawater group(SG), and dexamethasone treatment group (DG). Animals in CG group only had open chest trauma, those in the SG group were exposed to seawater after open chest trauma, and those in the DG group were treated with dexamethasone (1 mg/kg) after exposed to seawater. The vital signs of animals, plasma osmotic pressure, lung permeability index (LPI), and peripheral white blood cell count were observed 0,2,4,6, and 8 h after trauma. The plasma samples and bronchoalveolar lavage fluid (BALF) were collected for testing the levels of cytokines (IL-1ß, IL-8, and vWF, etc.) with ELISA kit. H-E staining was used to observe the pathological changes of the lung. Results: Compared with the SG group, the pathological changes were improved in the DG group; the plasma osmotic pressures were similar between the two groups; and the pulmonary permeability index was markedly decreased in the DG group (0.039±0.006 vs 0.055±0.002, P<0.05). Besides,the count of peripheral leukocyte(X 109) and plasma IL-Iß, IL-8, and vWF(pg/ml) were all markedly decreased in the DG group compared with the SG group(WBC: 21.52± 3.21 vs 24.8±2.08; IL-Iß:72. 84±38.42 vs 131.90±35.39; IL-8:45.21± 16.39 vs 88.26± 6.66;vWF:0.47±0.08 vs 1.03± 0.09,P< 0.05). Conclusion: Early dexamethasone treatment can attenuate the inflammatory injury of the lung in dogs with open chest trauma after seawater immersion, providing more chance for further management.
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Objective To evaluate the effects of interleukin-10 and dexamethasone on expression of TNF-? mRNA, IL-1? mRNA, and IL-1ra mRNA in acute lung injury (ALI). Methods A rat model of ALI was reproduced by intratracheal instillation of endotoxin (LPS) with a dose of 10mg/kg. 72 male S-D rats were randomly divided into control group, LPS group, LPS+IL-10 group, and LPS+Dex group, 18 rats in each group (6 rats at 2h, 6h, and 24h respectively). RT-PCR method was used to determine the expression of TNF-? mRNA, IL-1? mRNA, and IL-1ra mRNA in lung tissue. Results In LPS group TNF-? mRNA expression peaked at 2h, then decreased sharply; IL-1? mRNA expression increased markedly at 2h, peaked at 6h, then decreased; IL-1ra mRNA expression increased and peaked at 6h, and remained higher than control group at 24h. Both IL-10 and Dex inhibited TNF-? mRNA and IL-1? mRNA expression, but with no effect on IL-1ra mRNA expression. Pathological examination revealed that IL-10 or Dex attenuated injury to lung parenchyma. Conclusions The up-regulation of expression of both TNF-? mRNA and IL-1? mRNA was much earlier than that of the expression of IL-1ra mRNA, suggesting that there was an imbalance of inflammatory and anti-inflammatory mediators in the early phase of ALI. Both IL-10 and Dex could inhibit the expression of inflammatory mediators and exert no effect on the expression of anti-inflammatory mediators, thus contributing a balance effect between them and relieving ALI in rats.
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Objective To investigate changes in glucocorticoid receptor (GR) expression and activity in lung tissue of acute lung injury induced by lipopolysaccharide (LPS) within 24h in rat. Methods A total of 70 Wistar rats were divided randomly into LPS treatment group and LPS+ Dexamethasone (Dex) treatment group. The GR mRNA and GR protein expressions in the lung tissue of LPS challenged rats were assessed by RT-PCR and Western blot at different time points. Electrophoretic mobility shift assays (EMSA) were used to determine the GR activity in the lung tissue. Results The expression level of GR mRNA was depressed, but it returned to normal level at 24h after LPS challenge. The expression level of GR was also lowered, reaching the lowest level at 8h. GR activity was decreased, reaching the lowest level at 1h, and remaining lower than that of normal control at 24h. Dex treatment showed no obvious effect on GR activity during the late period of treatment. Conclusion The GR protein expression decreases in lung tissue of acute lung injury in rats, and it maybe associated with the decreased expression of mRNA and accelerated degradation of GR protein. The activity of GR is inhibited sharply, resulting in glucocorticoid resistance.