Role of pyroptosis pathway related molecules in acute lung injury induced by gas explosion in rats / 中华劳动卫生职业病杂志

Objective: To explore the role and significance of pyroptosis in gas explosion-induced acute lung injury (ALI) in rats. Methods: In February 2018, 126 SPF male SD rats were selected and randomly divided into blank control group (18 rats) and experimental group (40 m, 80 m, 120 m, 160 m, 200 m and 240 m, 18 per group) . The experimental group carried out gas explosion in the roadway to build the ALI model, the control group did not carry out gas explosion, and other conditions were consistent with the experimental group. Respiratory function indexes such as respiratory frequency (f) , tidal volume (TV) , minute ventilation (MV) and airway stenosis index (Penh) were measured 24 hours after the explosion. 5 rats in each group were sacrificed after anesthesia, Hematoxylin-Eosin (HE) staining was used to observe the pathological morphology of lung tissue. Immunohistochemistry was used to detect the content of Caspase-1. Western blotting was used to detect the content of cell pyroptosis including nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) , Caspase-1, interleukin-1β (IL-1β) and interleukin-18 (IL-18) in lung tissue related protein expression. Results: The f and MV of rats in the experimental group were higher than those in the control group (P<0.05) . Except for the 40 m and 80 m groups, the TV of rats in the other experimental groups were higher than those in the control group (P<0.05) . Except for the 40 m group, the Penh of rats in the experimental groups were lower than those in the control group (P<0.05) . HE staining showed that the lung tissue of the experimental groups at different distance points showed obvious edema of the pulmonary interstitium and alveoli, a large number of red blood cells and inflammatory cells exuded in the alveolar space, thickening of the pulmonary interstitium, and increased lung injury score (P<0.05) . The results of immunohistochemistry showed that the positive expression of Caspase-1 in each experimental group was higher than that in the control group (P<0.05) . Western blotting results showed that the expression of pyroptosis-related proteins in each experimental group was higher than that in the control group (P<0.05) . Conclusion: Pyroptosis is involved in the pathophysiological process of gas explosion-induced ALI in rats.

Induction of selective liver hypothermia prevents significant ischemia/reperfusion injury in Wistar rats after 24 hours

Purpose To investigate the effects of induction of selective liver hypothermia in a rodent model. Methods Seven male Wistar rats were subjected to 90 minutes of partial 70% liver ischemia and topic liver 26°C hypothermia (H group). Other seven male Wistar rats were subjected to 90 minutes of partial 70% normothermic liver ischemia (N group). Five additional rats underwent a midline incision and section of liver ligaments under normothermic conditions and without any liver ischemia (sham group). All animals were sacrificed 24-h after reperfusion, and livers were sampled for analyses. Pathology sections were scored for sinusoidal congestion, ballooning, hepatocelllular necrosis and the presence of neutrophilic infiltrates. Results At the end of the experiment, liver tissue expressions of TNF-ɑ, IL-1β, iNOS and TNF-ɑ/IL-10 ratio were significantly reduced in the H group compared to N group, whereas IL-10 and eNOS were significantly increased in H group. Histopathological injury scores revealed a significant decrease in ischemia/reperfusion (I/R) injuries in H group. Conclusion Selective liver hypothermia prevented I/R injury by inhibiting the release of inflammatory cytokines, preserves microcirculation, prevents hepatocellular necrosis and leukocyte infiltration, allowing maintenance of the liver architecture.

Inflammatory lung injury in rabbits: effects of high-frequency oscillatory ventilation in the prone position / Lesão inflamatória pulmonar em coelhos: efeitos da ventilação oscilatória de alta frequência em posição prona

ABSTRACT Objective: To compare the effects that prone and supine positioning during high-frequency oscillatory ventilation (HFOV) have on oxygenation and lung inflammation, histological injury, and oxidative stress in a rabbit model of acute lung injury (ALI). Methods: Thirty male Norfolk white rabbits were induced to ALI by tracheal saline lavage (30 mL/kg, 38°C). The injury was induced during conventional mechanical ventilation, and ALI was considered confirmed when a PaO2/FiO2 ratio < 100 mmHg was reached. Rabbits were randomly divided into two groups: HFOV in the supine position (SP group, n = 15); and HFOV with prone positioning (PP group, n = 15). For HFOV, the mean airway pressure was initially set at 16 cmH2O. At 30, 60, and 90 min after the start of the HFOV protocol, the mean airway pressure was reduced to 14, 12, and 10 cmH2O, respectively. At 120 min, the animals were returned to or remained in the supine position for an extra 30 min. We evaluated oxygenation indices and histological lung injury scores, as well as TNF-α levels in BAL fluid and lung tissue. Results: After ALI induction, all of the animals showed significant hypoxemia, decreased respiratory system compliance, decreased oxygenation, and increased mean airway pressure in comparison with the baseline values. There were no statistically significant differences between the two groups, at any of the time points evaluated, in terms of the PaO2 or oxygenation index. However, TNF-α levels in BAL fluid were significantly lower in the PP group than in the SP group, as were histological lung injury scores. Conclusions: Prone positioning appears to attenuate inflammatory and histological lung injury during HFOV in rabbits with ALI.

RESUMO Objetivo: Comparar os efeitos das posições prona e supina durante ventilação oscilatória de alta frequência (VOAF) sobre oxigenação e inflamação pulmonar, lesão histológica e estresse oxidativo em um modelo de lesão pulmonar aguda (LPA) em coelhos. Métodos: Trinta coelhos Norfolk machos brancos foram submetidos à LPA por meio de lavagem traqueal com salina (30 ml/kg, 38°C). A lesão foi induzida durante a ventilação mecânica convencional, e a LPA foi considerada confirmada na presença de relação PaO2/FiO2 < 100 mmHg. Os coelhos foram aleatoriamente divididos em dois grupos: VOAF em posição supina (grupo PS, n = 15); e VOAF em posição prona (grupo PP, n = 15). Para a VOAF, a pressão média das vias aéreas foi inicialmente estabelecida em 16 cmH2O. No 30º, 60º e 90º min após o início do protocolo de VOAF, a pressão média das vias aéreas foi reduzida para 14, 12 e 10 cmH2O, respectivamente. No 120º min, os animais foram recolocados ou permaneceram na posição supina por mais 30 min. Foram avaliados os índices de oxigenação e escores histológicos de lesão pulmonar, bem como os níveis de TNF-α em lavado broncoalveolar e tecido pulmonar. Resultados: Após a indução da LPA, todos os animais apresentaram hipoxemia significativa, diminuição da complacência do sistema respiratório, diminuição da oxigenação e aumento da pressão média das vias aéreas em comparação aos valores basais. Não houve diferenças estatisticamente significativas entre os dois grupos, em nenhum dos momentos avaliados, quanto a PaO2 e índice de oxigenação. Entretanto, os níveis de TNF-α no lavado broncoalveolar foram significativamente menores no grupo PP que no grupo PS, assim como os escores histológicos de lesão pulmonar. Conclusões: A posição prona parece atenuar a lesão pulmonar inflamatória e histológica durante a VOAF em coelhos com LPA.

Glycogen synthase kinase-3 beta inhibitors protectagainst the acute lung injuries resulting from acute necrotizing pancreatitis

Abstract Purpose The research is intended for clarification of the efficacy as well as the underlying mechanism of GSK-3β inhibitors on the advancement of acute lung injuries in acute necrotizing pancreatitis (ANP) in rats. Methods Seventy-two rats were randomly divided into 6 groups: (1)ANP-vehicle; (2)ANP-TDZD-8;(3)ANP-SB216763;(4)Sham-vehicle;(5)Sham-TDZD-8;(6)Sham-SB216763; Blood biochemical test, histopathological examination and immunohistochemical analysis of rats pancreas and lung tissues were performed. The protein expression of GSK-3β, phospho-GSK-3β (Ser9), iNOS, ICAM-1, TNF-α, and IL-10 were detected in lung tissues by Western-blot. Results The outcomes revealed that the intervention of GSK-3β inhibitors alleviated the pathological damage of pancreas and lung (P<0.01), reduced serum amylase, lipase, hydrothorax and lung Wet-to-Dry Ratio, attenuated serum concentrations of IL-1β and IL-6 (P<0.01), inhibited the activation of NF-κB, and abated expression of iNOS, ICAM-1 and TNF-α protein, but up-regulated IL-10 expression in lung of ANP rats (P<0.01). The inflammatory response and various indicators in ANP-TDZD-8 groups were lower than those in ANP-SB216763 groups. Conclusions Inhibition of GSK-3β weakens acute lung injury related to ANP via the inhibitory function of NF-κB signaling pathway. Different kinds of GSK-3β inhibitors have different effects to ANP acute lung injury.

Apoptotic mechanisms in rabbits with blast-induced acute lung injury

Abstract Purpose: To investigate the apoptotic mechanisms in rabbits with blast-induced acute lung injury (ALI). Methods: A total of 40 rabbits were randomly divided into a blank control group (A, n=10) and an experimental group (EXP, n=30). Explosion-induced chest-ALI models were prepared and sampled at different time points (4, 12, and 24h after modeling, T1-T3) to test the lung dry weight/wet weight ratio (W/D) and arterial oxygen pressure (PaO2), apoptosis of lung tissue by the TUNEL assay, and Caspase-3, Bax, and Bcl-2 levels by immunohistochemical analysis. Furthermore, lung tissue was sampled to observe pathological morphology by microscopy. Results: Under a light microscope, Group EXP exhibited obvious edema in the pulmonary interstitial substance and alveoli, a large number of red blood cells, inflammatory cells, and serous exudation in the alveolar cavity, as well as thickening of the pulmonary interstitial fluid. Compared to Group A, the W/D ratio was significantly increased in Group EXP (P<0.01), while PaO2 was significantly reduced (P<0.01). The apoptosis index was significantly increased (P<0.01), and caspase-3 and Bax/Bcl-2 levels were increased (P<0.01). Conclusion: Apoptosis plays an important role in the occurrence and development of acute lung injury in rabbits by participating in lung injury and promoting the progression of ALI.

Total phenolic, flavonoid, alkaloid and iridoid content and preventive effect of Lider-7-tang on lipopolysaccharide-induced acute lung injury in rats

Lider-7-tang, a medicine used for the treatment of respiratory diseases especially pneumonia and fever in Mongolian Traditional Medicine, was selected for this phytochemical and pharmacological study. The objectives of the study were to determine total biological active substances and analyze the effects of Lider-7-tang treatment in rats with acute lung injury (ALI). Quantitative determination of the total active constituents (phenolic, flavonoid, iridoid and alkaloid) of the methanol extract of Lider-7-tang was performed using Folin-Ciocalteu reagent, aluminum chloride reagent, Trim-Hill reagent, and Bromocresol green reagent, respectively. A total of fifty 8-10-week-old male Wistar rats (200-240 g) were randomized into three groups: control group, lipopolysaccharide (LPS) group (7.5 mg/kg) and LPS+Lider-7 group (90 mg/kg Lider-7-tang before LPS administration). The total content of alkaloids was 0.2±0.043%, total phenols 7.8±0.67%, flavonoids 3.12±0.206%, and iridoids 0.308±0.0095%. This study also evaluated the effects of Lider-7 on levels of inflammatory mediators by observing histopathological features associated with LPS-induced ALI. The rats pretreated with Lider-7 had significantly lower levels of IL-6 (at 3 and 6 h), and TNF-α (at 3, 6, 9, and 12 h). The current study showed that Lider-7 exerted a preventive effect against LPS-induced ALI, which appeared to be mediated by inhibiting the release of pro-inflammatory cytokines.

Galantamine protects against lipopolysaccharide-induced acute lung injury in rats

Lipopolysaccharide (LPS)-induced endotoxemia triggers the secretion of proinflammatory cytokines and can cause acute lung injury (ALI). The high mobility group box 1 (HMGB1) protein plays an important role as a late mediator of sepsis and ALI. Galantamine (GAL) is a central acetylcholinesterase inhibitor that inhibits the expression of HMGB1. This study evaluated the effects of GAL by measuring levels of inflammatory mediators and observing histopathological features associated with LPS-induced ALI. Sixty 8-10 week old male Sprague-Dawley rats (200-240 g) were randomized into three groups as follows: control group, LPS group (7.5 mg/kg LPS), and LPS+GAL group (5 mg/kg GAL before LPS administration). Histopathological examination of lung specimens obtained 12 h after LPS administration was performed to analyze changes in wet-to-dry (W/D) weight ratio, myeloperoxidase (MPO) activity, and HMGB1 expression level. Additionally, plasma concentrations of tumor necrosis factor-α, interleukin-6, and HMGB1 were measured using an enzyme-linked immunosorbent assay at 0 (baseline), 3, 6, 9, and 12 h after LPS administration. Mortality in the three groups was recorded at 72 h. LPS-induced ALI was characterized by distortion of pulmonary architecture and elevation of MPO activity, W/D weight ratio, and levels of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-6, and HMGB1. Pretreatment with GAL significantly reduced the LPS-induced lung pathological changes, W/D weight ratio, levels of pro-inflammatory cytokines and MPO activity (ANOVA). Moreover, GAL treatment significantly decreased the mortality rate (ANOVA). In conclusion, we demonstrated that GAL exerted a protective effect on LPS-induced ALI in rats.

Effects of CpG oligodeoxynucleotide 1826 on acute radiation-induced lung injury in mice

BACKGROUND: The radiation-induced lung injury is a common complication from radiotherapy in lung cancer. CpG ODN is TLR9 activator with potential immune modulatory effects and sensitization of radiotherapy in lung cancer. This study aimed to examine the effect of CpG ODN on acute radiation-induced lung injury in mice. METHODS AND RESULTS: The mouse model of radiation-induced lung injury was established by a single dose of 20 Gy X-rays exposure to the left lung. The results showed that the pneumonia score was lower in RT+CpG group than in RT group on 15th and 30th days. Compared with RT group, CpG ODN reduced the serum concentrations of MDA (P < 0.05) and increased the serum concentrations of SOD, GSH (P < 0.05). The serum concentration of TNF-α in RT+CpG group was lower on 15th and 30th days post-irradiation (P < 0.05). CONCLUSION: The study demonstrated that CpG ODN has preventive effects of acute radiation-induced lung injury in mice. Lung inflammatory reaction and oxidative stress are promoted in the initiation of radiation-induced pneumonia. CpG ODN may reduce the injury of reactive oxygen species and adjust the serum TNF-α concentration in the mice after irradiation, which reduces the generation of the inflammatory cytokines.

Effect of hypertonic saline treatment on the inflammatory response after hydrochloric acid-induced lung injury in pigs

OBJECTIVES: Hypertonic saline has been proposed to modulate the inflammatory cascade in certain experimental conditions, including pulmonary inflammation caused by inhaled gastric contents. The present study aimed to assess the potential anti-inflammatory effects of administering a single intravenous dose of 7.5% hypertonic saline in an experimental model of acute lung injury induced by hydrochloric acid. METHODS: Thirty-two pigs were anesthetized and randomly allocated into the following four groups: Sham, which received anesthesia and were observed; HS, which received intravenous 7.5% hypertonic saline solution (4 ml/kg); acute lung injury, which were subjected to acute lung injury with intratracheal hydrochloric acid; and acute lung injury + hypertonic saline, which were subjected to acute lung injury with hydrochloric acid and treated with hypertonic saline. Hemodynamic and ventilatory parameters were recorded over four hours. Subsequently, bronchoalveolar lavage samples were collected at the end of the observation period to measure cytokine levels using an oxidative burst analysis, and lung tissue was collected for a histological analysis. RESULTS: Hydrochloric acid instillation caused marked changes in respiratory mechanics as well as blood gas and lung parenchyma parameters. Despite the absence of a significant difference between the acute lung injury and acute lung injury + hypertonic saline groups, the acute lung injury animals presented higher neutrophil and tumor necrosis factor alpha (TNF-α), interleukin (IL)-6 and IL-8 levels in the bronchoalveolar lavage analysis. The histopathological analysis revealed pulmonary edema, congestion and alveolar collapse in both groups; however, the differences between groups were not significant. Despite the lower cytokine and neutrophil levels observed in the acute lung injury + hypertonic saline group, significant differences were not observed among the treated and non-treated groups. ...

Therapeutic effects of compound hypertonic saline on rats with sepsis

Sepsis is one of the major causes of death and is the biggest obstacle preventing improvement of the success rate in curing critical illnesses. Currently, isotonic solutions are used in fluid resuscitation technique. Several studies have shown that hypertonic saline applied in hemorrhagic shock can rapidly increase the plasma osmotic pressure, facilitate the rapid return of interstitial fluid into the blood vessels, and restore the effective circulating blood volume. Here, we established a rat model of sepsis by using the cecal ligation and puncture approach. We found that intravenous injection of hypertonic saline dextran (7.5% NaCl/6% dextran) after cecal ligation and puncture can improve circulatory failure at the onset of sepsis. We found that the levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 and intracellular adhesion molecule 1 levels in the lung tissue of cecal ligation and puncture rats treated with hypertonic saline dextran were significantly lower than the corresponding levels in the control group. We inferred that hypertonic saline dextran has a positive immunoregulatory effect and inhibits the overexpression of the inflammatory response in the treatment of sepsis. The percentage of neutrophils, lung myeloperoxidase activity, wet to dry weight ratio of lung tissues, histopathological changes in lung tissues, and indicators of arterial blood gas analysis was significantly better in the hypertonic saline dextran-treated group than in the other groups in this study. Hypertonic saline dextran-treated rats had significantly improved survival rates at 9 and 18 h compared to the control group. Our results suggest that hypertonic saline dextran plays a protective role in acute lung injury caused after cecal ligation and puncture. In conclusion, hypertonic/hyperoncotic solutions have beneficial therapeutic effects in the treatment of an animal model of sepsis.

Exogenous normal lymph alleviates lipopolysaccharide-induced acute lung injury through lessening the adhesion molecules

PURPOSE: To evaluate the role of exogenous normal lymph (ENL) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats. METHODS: ALI was induced by the jugular vein injection of LPS (iv, 15 mg/kg) in rats of the LPS and LPS+ENL groups within 15 min, then, ENL without cell components (5 ml/kg) was infused at the speed of 0.5 ml per minute in the LPS+ENL group, the same amount of saline was administered in the LPS group. The rats in the sham group received the same surgical procedure and saline. The histomorphology and the levels of P-selectin, intercellular adhesion molecule-1 (ICAM-1), myeloperoxidase (MPO) in pulmonary tissue were assessed. RESULTS: LPS induced pulmonary injury as well as increased the wet/dry weight ratio (W/D) and the levels of P-selectin, ICAM-1, and MPO in pulmonary tissues. These deleterious effects of LPS were significantly ameliorated by ENL treatment. CONCLUSION: Exogenous normal lymph could markedly alleviate the acute lung injury induced by lipopolysaccharide, and its effects might be related to lessening the adhesion molecules. .

Effects of Transglutaminase 2 Inhibition on Ventilator-Induced Lung Injury

This study was performed to examine the role of transglutaminase 2 (TG2) in ventilator-induced lung injury (VILI). C57BL/6 mice were divided into six experimental groups: 1) control group; 2) lipopolysaccharide (LPS) group; 3) lung protective ventilation (LPV) group; 4) VILI group; 5) VILI with cystamine, a TG2 inhibitor, pretreatment (Cyst+VILI) group; and 6) LPV with cystamine pretreatment (Cyst+LPV) group. Acute lung injury (ALI) score, TG2 activity and gene expression, inflammatory cytokines, and nuclear factor-kappaB (NF-kappaB) activity were measured. TG2 activity and gene expression were significantly increased in the VILI group (P < 0.05). Cystamine pretreatment significantly decreased TG2 activity and gene expression in the Cyst+VILI group (P < 0.05). Inflammatory cytokines were higher in the VILI group than in the LPS and LPV groups (P < 0.05), and significantly lower in the Cyst+VILI group than the VILI group (P < 0.05). NF-kappaB activity was increased in the VILI group compared with the LPS and LPV groups (P < 0.05), and significantly decreased in the Cyst+VILI group compared to the VILI group (P = 0.029). The ALI score of the Cyst+VILI group was lower than the VILI group, but the difference was not statistically significant (P = 0.105). These results suggest potential roles of TG2 in the pathogenesis of VILI.

Propofol exerts anti-inflammatory effects in rats with lipopolysaccharide-induced acute lung injury by inhibition of CD14 and TLR4 expression

We investigated the effect of propofol (Prop) administration (10 mg kg-1 h-1, intravenously) on lipopolysaccharide (LPS)-induced acute lung injury and its effect on cluster of differentiation (CD) 14 and Toll-like receptor (TLR) 4 expression in lung tissue of anesthetized, ventilated rats. Twenty-four male Wistar rats were randomly divided into three groups of 8 rats each: control, LPS, and LPS+Prop. Lung injury was assayed via blood gas analysis and lung histology, and tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels were determined in bronchoalveolar lavage fluid using ELISA. Real-time polymerase chain reaction was used to detect CD14 and TLR4 mRNA levels, and CD14 and TLR4 protein expression was determined by Western blot. The pathological scores were 1.2 ± 0.9, 3.3 ± 1.1, and 1.9 ± 1.0 for the control, LPS, and LPS+Prop groups, respectively, with statistically significant differences between control and LPS groups (P < 0.05) and between LPS and LPS+Prop groups (P < 0.05). The administration of LPS resulted in a significant increase in TNF-α and IL-1β levels, 7- and 3.5-fold, respectively (P < 0.05), while treatment with propofol partially blunted the secretion of both cytokines (P < 0.05). CD14 and TLR4 mRNA levels were increased in the LPS group (1.48 ± 0.05 and 1.26 ± 0.03, respectively) compared to the control group (1.00 ± 0.20 and 1.00 ± 0.02, respectively; P < 0.05), while propofol treatment blunted this effect (1.16 ± 0.05 and 1.12 ± 0.05, respectively; P < 0.05). Both CD14 and TLR4 protein levels were elevated in the LPS group compared to the control group (P < 0.05), while propofol treatment partially decreased the expression of CD14 and TLR4 protein versus LPS alone (P < 0.05). Our study indicates that propofol prevents lung injury, most likely by inhibition of CD14 and TLR4 expression.

Lesão pulmonar aguda induzida pela administração endovenosa de extrato da fumaça do cigarro / Acute lung injury induced by the intravenous administration of cigarette smoke extract

OBJETIVO: Investigar os efeitos agudos da administração endovenosa de extrato da fumaça do cigarro (EFC) em parâmetros funcionais respiratórios, inflamatórios e histológicos em ratos e comparar esse potencial modelo de lesão pulmonar aguda (LPA) com aquele com o uso de ácido oleico (AO). MÉTODOS: Foram estudados 72 ratos Wistar machos divididos em quatro grupos: tratados somente com soro fisiológico (SF; grupo controle); tratados com EFC e SF (grupo EFC); tratados com SF e AO (grupo AO); e tratados com EFC e AO (grupo EFC/AO). RESULTADOS: As médias de complacência foram significantemente menores nos grupos AO e EFC/AO (2,12 ± 1,13 mL/cmH2O e 1,82 ± 0,77 mL/cmH2O, respectivamente) do que no controle (3,67 ± 1,38 mL/cmH2O). A proporção de neutrófilos e a atividade das metaloproteinases 2 e 9 em lavado broncoalveolar foram significantemente maiores nos grupos AO e EFC/AO que no controle. O acometimento pulmonar avaliado por morfometria foi significantemente maior nos grupos AO e EFC/AO (72,9 ± 13,8% e 77,6 ± 18,0%, respectivamente) do que nos grupos controle e EFC (8,7 ± 4,1% e 32,7 ± 13,1%, respectivamente), e esse acometimento foi significantemente maior no grupo EFC que no grupo controle. CONCLUSÕES: A administração endovenosa de EFC, nas doses e tempos deste estudo, associou-se à LPA mínima. O EFC não potencializou a LPA induzida por AO. Estudos adicionais são necessários para esclarecer o papel potencial desse modelo como método de estudo dos mecanismos de agressão pulmonar pelo tabaco.

OBJECTIVE: To investigate the acute effects of intravenous administration of cigarette smoke extract (CSE) on histological, inflammatory, and respiratory function parameters in rats, as well as to compare this potential acute lung injury (ALI) model with that with the use of oleic acid (OA). METHODS: We studied 72 Wistar rats, divided into four groups: control (those injected intravenously with saline); CSE (those injected intravenously with CSE and saline); OA (those injected intravenously with saline and OA); and CSE/OA (those injected intravenously with CSE and OA). RESULTS: Mean lung compliance was significantly lower in the OA and CSE/OA groups (2.12 ± 1.13 mL/cmH2O and 1.82 ± 0.77 mL/cmH2O, respectively) than in the control group (3.67 ± 1.38 mL/cmH2O). In bronchoalveolar lavage fluid, the proportion of neutrophils was significantly higher in the OA and CSE/OA groups than in the control group, as was the activity of metalloproteinases 2 and 9. Pulmonary involvement, as assessed by morphometry, was significantly more severe in the OA and CSE/OA groups (72.9 ± 13.8% and 77.6 ± 18.0%, respectively) than in the control and CSE groups (8.7 ± 4.1% and 32.7 ± 13.1%, respectively), and that involvement was significantly more severe in the CSE group than in the control group. CONCLUSIONS: The intravenous administration of CSE, at the doses and timing employed in this study, was associated with minimal ALI. The use of CSE did not potentiate OA-induced ALI. Additional studies are needed in order to clarify the potential role of this model as a method for studying the mechanisms of smoking-induced lung injury.

Acute pulmonary injury induced by experimental muscle trauma / Lesão pulmonar aguda induzida por trauma muscular experimental

PURPOSE: To develop an easily reproducible model of acute lung injury due to experimental muscle trauma in healthy rats. METHODS: Eighteen adult Wistar rats were randomized in 3 groups (n=6): G-1- control, G-2 - saline+trauma and G-3 - dexamethasone+trauma. Groups G-1 and G-2 were treated with saline 2,0ml i.p; G-3 rats were treated with dexamethasone (DE) (2 mg/kg body weight i.p.). Saline and DE were applied 2h before trauma and 12h later. Trauma was induced in G-2 and G-3 anesthetized (tribromoethanol 97 percent 100 ml/kg i.p.) rats by sharp section of anterior thigh muscles just above the knee, preserving major vessels and nerves. Tissue samples (lung) were collected for myeloperoxidase (MPO) assay and histopathological evaluation. RESULTS: Twenty-four hours after muscle injury there was a significant increase in lung neutrophil infiltration, myeloperoxidase activity and edema, all reversed by dexamethasone in G-3. CONCLUSION: Trauma by severance of thigh muscles in healthy rats is a simple and efficient model to induce distant lung lesions.

OBJETIVO: Desenvolver um modelo facilmente reprodutível de lesão pulmonar aguda decorrente de trauma muscular experimental em ratos sadios. MÉTODOS: Dezoito ratos Wistar adultos foram randomizados em 3 grupos (n=6): G-1-controle, G-2 - trauma+salina e G-3 - trauma+dexametasona. Grupos G-1 e G-2 foram tratados com salina 2,0 ml ip, G-3 ratos foram tratados com dexametasona (DE) (2 mg/kg peso corporal ip). Salina e DE foram aplicadas 2h antes e 12h depois do trauma. Trauma foi induzido em ratos G-2 e G-3 anestesiados (tribromoetanol 97 por cento de 100 ml/kg, i.p.) por secção da musculatura anterior da coxa logo acima da articulação do joelho, preservando os grandes vasos e nervos. Amostras de tecido (pulmão) foram coletadas para avaliação da mieloperoxidase (MPO), e exames histopatológicos. RESULTADOS: Vinte e quatro horas após a indução da lesão muscular houve um aumento significativo na infiltração de neutrófilos pulmonares, atividade da mieloperoxidase e edema, todos revertidos por dexametasona, no G-3. CONCLUSÃO: O trauma decorrente da secção dos músculos da coxa em ratos saudáveis é um modelo simples e eficaz para induzir lesões pulmonares à distância.

Aspectos histomorfológicos e respiratórios em modelo de lesão pulmonar aguda por sepse em ratos tratados com pentoxifilina / Histomorphologic and respiratory aspects of acute lung injury in rats induced by experimental sepsis and under pentoxifylline treatment

OBJETIVO: Analisar as alterações histomorfológicas e respiratórias em modelo de lesão pulmonar aguda por sepse em ratos tratados com pentoxifilina. MÉTODOS: Foram utilizados 15 ratos adultos distribuídos em três grupos (n=5, por grupo), assim constituídos: GC - receberam apenas ventilação mecânica; GS - Animais sépticos tratados com solução salina e mecanicamente ventilados; GS+PTX - Animais sépticos, com infusão de pentoxifilina e mecanicamente ventilados. Todos os animais foram ventilados por um período de 180 minutos. Ao final deste período, foram avaliadas variáveis gasométricas (gasometria arterial), gravimétricas (relação peso úmido/peso seco), concentração de proteínas totais no lavado broncoalveolar e histomorfométricas (espessura dos septos alveolares). Os dados obtidos foram submetidos a análise estatística (P < 0,05) RESULTADOS: A pressão parcial de oxigênio ao final do experimento mostrou-se elevada no grupo GS+PTX (460,0 ± 38,2 mmHg) em relação ao grupo GS (336,0 ± 14,6 mmHg) (P < 0,05). No grupo GS, a concentração de proteínas no lavado broncoalveolar encontrou-se aumentada em relação aos demais grupos; no entanto, se mostrou atenuada após a administração de pentoxifilina. Notamos, pela morfologia em todos os grupos avaliados, vasodilatação nos septos alveolares e no grupo S alguns alvéolos apresentaram-se repletos de macrófagos. Estes aspectos foram atenuados no GS+PTX. A espessura dos septos alveolares mostrou uma significante redução no grupo GS+PTX quando comparado com o grupo GS (P < 0,05). CONCLUSÃO: A pentoxifilina restabelece a oxigenação e reduz os efeitos deletérios do processo de sepse em associação à ventilação mecânica com baixo volume corrente.

OBJECTIVE: Respiratory repercussion on acute lung injury in a model of induced sepsis intraperitoneally. METHODS: Fifteen animals taken at random were submitted to adult male Wistar rats. The rats were randomly divided into 3 groups (n=15): Group C - control group received only mechanical ventilation; Group S - rats received live Escherichia coli (E. coli) intraperitoneally (septic) and after 6 hours they were treated with normal saline infusion and ventilated with a low tidal volume. Group S+PTX - rats received live Escherichia coli intraperitoneally (septic) and after 6 hours they were treated with pentoxifylline (PTX) infusion and ventilated with a low tidal volume. All animals were ventilated during 180 minutes. We analyzed the arterial blood gases, gravimetric indices and histomorphometric analysis. RESULTS: Blood gases, wet to dry ratios, and total protein concentrations in the bronchoalveolar lavage were analyzed in all experimental groups. In the end of the experiment the partial pressure of oxygen was higher in the GS+PTX (460,0 ± 38,2 mmHg) compared with GS (336,0 ± 14,6 mmHg). Pentoxifylline with low tidal volume attenuated significantly total protein in the bronchoalveolar lavage. The septal diameter was significantly reduced in the group GS compared with group GS+PTX (P < 0,05). CONCLUSIONS:The pentoxifylline ameliorated the oxygenation and decreased the deleterious effects of sepsis in the associated mechanical ventilation.