Navegando por Palavras-chave "Modelo Experimental"

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    Efeito do aumento da massa corporal na resposta pulmonar e no tecido adiposo em camundongos
    (Universidade Federal de São Paulo (UNIFESP), 2019-09-05) Escrobat, Ticiana Carvalho Pereira [UNIFESP]; Prado, Carla Máximo [UNIFESP]; http://lattes.cnpq.br/1740478426977844; Universidade Federal de São Paulo (UNIFESP)
    Introduction: Obesity is a complex syndrome that poses a serious risk to health, and a better understanding of its consequences is necessary. It is known that there is a relationship between obesity and worsening of pulmonary disease, but obesity-induced lung alterations per se have been poorly investigated. Pulmonary inflammation is a pathophysiological characteristic of various diseases such as asthma and COPD (chronic obstructive pulmonary disease). Our hypothesis is that the body mass gain induced by a sucrose-rich diet can, per se, induce inflammatory and morphological changes in the lung. Aim: To evaluate the inflammation and pulmonary morphology of animals submitted to a high caloric high sucrose diet. Methods: Male C57BL/6 mice were submitted to a high caloric high sucrose diet (Obese) or to a standard diet of Nuvilab CR1 (Control). At the end of the protocol, body mass gain, metabolic indexes, visceral adiposity index in the liver and pro and anti-inflammatory cytokines in adipose tissue and liver were evaluated by ELISA. We also evaluated the inflammation (cells and cytokines by ELISA) and morphological alterations in the lung. Results: The animals submitted to the high caloric high sucrose diet had an increase in body mass and visceral adiposity index in the liver compared with control group (p<0.05 and p<0.005, respectively). There was no difference in fasting glycemia between groups, however, animals from obese group showed an increase in the area under the curve in the oral glucose tolerance test and increase in total cholesterol and HDL fraction compared with control (p<0.05). There was no increase in the level of cytokines in epididymal and subcutaneous adipose tissue (TNF-α, IL-6 and IL-10) and in the liver (IL-6 and IL-10) in the obese group. In lung tissue of obese animals, there was an increase in total protein in the lung (p<0.05), in addition to peribronchial edema and increase of polymorphonuclear cells around the airways (p≤0.001 and p<0.05). There was also an increase in bronchoconstriction index (p<0.05), collagen deposition (p<0.05) and increase in smooth muscle thickness in the airways (p<0.05) compared with Control. There was no increase in TNF-α, IL-6, IL-8 and IL-10 in bronchoalveolar lavage, however the concentration of IL-10 in the pulmonary homogenate was reduced in obese animals (p<0.05). Although there has been no increase in cytokines in adipose tissue, there was a positive correlation of gain mass with cytokines IL-6, IL-10 and TNF-α in epididymal adipose tissue (p<0.05). The gain mass also showed a positive correlation with the increase of edema and polymorphonuclear cells around the airways (p<0.05). Also, the increase in cholesterol had a negative correlation with the concentration of IL-10 in the lung tissue, which in turn presented negative correlation with thickening of the muscle layer (p<0.05). Finally, there were correlation between peribronchiolar edema and deposition of collagen fibers with the increase of polymorphonuclear cells and the bronchoconstriction index (p<0.05). Conclusion: The high caloric high sucrose diet induce gain mass without major metabolic and inflammatory changes in adipose tissue. Nevertheless, increased body mass induced significant morphological pulmonary changes, such as bronchoconstriction, edema, increase of polymorphonuclear cells and deposition of collagen fibers in the airways of these animals, which may impair pulmonary function even without causing an increase in cytokines in the lung. These data suggest that obese patients may present greater severity in the pulmonary response when subjected to stress induced by some pathological situation such as asthma or infection.
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    Mecanismos envolvidos no efeito do tratamento com Deidrodieugenol em modelo de asma mista
    (Universidade Federal de São Paulo (UNIFESP), 2020-03-05) Silva, Rafael Cossi Da [UNIFESP]; Prado, Carla Maximo [UNIFESP]; Universidade Federal de São Paulo
    Asthma is a disease characterized by bronchial inflammation and it still a public health problem even with the existence of a standard treatment consisting of corticosteroids and bronchodilators. Previously, our laboratory studies had shown that dehydrodieugenol, a dimer of the anti-inflammatory eugenol molecules, appears to be promising in reducing the neutrophil inflammatory response, with less toxicity than eugenol. Objectives. The present project aims to understand mechanisms involved in this model of mixed asthma and to test if the treatment with dehydrodieugenol will be effective in reducing inflammation. Materials and methods. Balb/c male mice, aged from 6 to 8 weeks, underwent to 24-day sensitization protocol, with ovalbumin and Freud's Adjuvant, for induction of mixed asthma. The dehydrodieugenol treatment were administered in the last four days, and the animals were euthanized on the last day of treatment. It was used animals sensitized with ovalbumin associated with Freud's adjuvant lungs, where essential cytokines in the pathophysiology of mixed asthma were evaluated, such as IL-1β, IL-8, IL-13, IL-4, IL-17, INF-γ, CXCL9 , CD68, TGF-β and IL-6; in addition to assessing the MAPK pathway in the lung. Finally, in histological sections, the pulmonary remodeling process was evaluated. Results. Compared to the ovoalbumin group, 10mg/kg dehydrodieugenol group decreased the levels of total cells (P <0.001), neutrophils (P <0.05), eosinophil (P <0.01), macrophages (P <0.01), lymphocytes (P <0.05), ERK1/2 phosphorylation (P <0.01), IL-1β cytokine levels (P <0.01), messenger RNA levels (P <0.05) and cytokines (P <0.01) of KC, levels of IL-6 messenger RNA (P <0.05), levels of INF-γ (P <0.01), levels of IL-13 cytokine (P <0.01), the levels of IL-4 messenger RNA (P <0.05), and a decrease in bronchoconstriction (P <0.001), smooth muscle thickness (P <0.01) and collagen deposition (P <0.05) in the airway. Conclusion. The results showed that the 10mg/kg dehydrodieugenol group decreased the inflammation more than 20mg/kg group. In addition, it was possible to perceive that in mixed asthma the most common inflammatory response is via Th1, justifying the resistance to standard treatment described in literature. Dehydrodieugenol has been shown to be efficient both in the inflammatory response and in the improvement of pulmonary remodeling, being an interesting molecule to be studied as an alternative treatment for patient diagnosed with mixed asthma.