Biblioteca Digital de Teses e Dissertações PÓS-GRADUAÇÃO SCTRICTO SENSU Programa de Pós-Graduação em Ciências Fisiológicas
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dc.creatorCUBA, Marília Beatriz de-
dc.creator.ID07698284697por
dc.contributor.advisor1GIRALDO, Luis Eduardo Ramirez-
dc.contributor.advisor1ID45642761668por
dc.contributor.advisor1Latteshttp://lattes.cnpq.br/8436042978241075por
dc.contributor.advisor-co1SILVA, Valdo José Dias dapor
dc.contributor.advisor-co1IDCPF:64003051653-
dc.date.accessioned2017-12-20T13:03:11Z-
dc.date.issued2012-08-13-
dc.identifier.citationCUBA, Marília Beatriz de. Efeitos da estimulação colinérgica com brometo de priridostigmina na cardiopatia chagásica crônica em camundongos. 2012. 103f. Dissertação (Mestrado em Ciências Fisiológicas) - Programa de Pós-Graduação em Ciências Fisiológicas, Universidade Federal do Triângulo Mineiro, Uberaba, 2012.por
dc.identifier.urihttp://bdtd.uftm.edu.br/handle/tede/463-
dc.description.resumoEmbora a patogênese da doença de Chagas seja altamente complexa e não seja completamente compreendida, é amplamente aceito que um equilíbrio entre a invasão do parasita e a resposta imune-inflamatória do hospedeiro desempenha um papel importante no desenvolvimento e evolução da doença. Nos últimos anos vários trabalhos na literatura vem destacando a marcada influência do sistema nervoso autonômico sobre o sistema imunológico em vários modelos experimentais de doenças com caráter inflamatório, sejam elas infecciosas ou auto-imunes, entre outras. Este trabalho teve como objeto de investigação avaliar os efeitos de modificações na neuroimunomodulação autonômica parassimpática, empregando o agente anti-colinesterásico brometo de piridostigmina, sobre a cardiopatia chagásica crônica experimental em camundongos. Para tal, camundongos C57BL/6j controles (Con) não tratados (NT), ou tratados com brometo de piridostigmina (Pirido) e camundongos C57BL/6j inoculados com formas tripomastigotas da cepa Romildo, respectivamente, de T. Cruzi (Chg) não tratados (NT), ou tratados com brometo de piridostigmina (Pirido) foram empregados. Todos os animais foram acompanhados por 6 meses e ao final submetidos à avaliação da presença de parasita sanguíneo e tecidual, eletrocardiograma (ECG) convencional sob anestesia, estudo da função autonômica cardíaca por meio de análise de variabilidade da frequência cardíaca e bloqueio autonômico farmacológico com atropina e propranolol, histopatologia do coração e quantificação de citocinas: fator de necrose tumoral-alfa (TNF-α), interferon gama (IFNγ), Interleucina 5(IL-5) e IL-10. Ao final do período de observação foi verificada uma significativa alteração do perfil eletrocardiográfico, autonômico e histopatológico, sugestivo de uma resposta inflamatória com desvio da resposta imune para o perfil Th1 nos animais do grupo Chg-NT em relação aos outros grupos estudados. Observouse que o tratamento crônico com o anticolinesterásico brometo de pirisdostigmina, nos animais Chg-Pirido, provocou uma redução significativa da resposta imune-inflamatório e fibrose no miocárdio, sem alterações do parasitismo sanguíneo e tissular, sugerindo uma redução da resposta imune perfil Th1 sem alteração do perfil Th2. Tal redução do perfil de resposta Th1 pode ser confirmada em parte pela diminuição nos níveis séricos de IFNγ e tendência a diminuição do TNF-α, sem alteração nos níveis de IL-10 nos animais Chg-Pirido, quando comparados aos Chg-NT. Concluindo, diante da análise em conjunto dos resultados apresentados, nossos achados confirmam a influência do papel neuroimuno-modulatório marcante do sistema nervoso autônomo parassimpático na evolução da resposta imune-inflamatória ao T. cruzi, durante a cardiopatia chagásica crônica experimental em camundongos.por
dc.description.abstractAlthough the pathogenesis of Chagas' disease is highly complex and not completely understood, it is widely accepted that a balance between the invasion of the parasite and the immune-inflammatory response of the host plays an important role in the development and progression of the disease. In recent years many studies in the literature has been highlighting the marked influence of the autonomic nervous system on the immune system in various experimental models of inflammatory diseases, whether infectious or autoimmune diseases, among others. This work had the object of investigation to assess the effects of changes in autonomic parasympathetic neuroimmunomodulation, employing the anti-cholinesterase pyridostigmine bromide on the experimental chronic Chagas' disease in mice. To this end, C57BL/6J mice controls (Con) non treated (NT), or treated with pyridostigmine bromide (Pyr) and C57BL/6J mice inoculated with trypomastigotes of Romildo strain, respectively, T. Cruzi (Chg) non treated (NT) or treated with pyridostigmine bromide (Pyr) were used. All animals were followed for 6 months and at the ending they were assessed for presence of blood and tissue parasites, conventional electrocardiogram (ECG) under anesthesia, study of cardiac autonomic function by means of analysis of heart rate variability and pharmacological autonomic blockade with atropine and propranolol, heart histopathology and quantification of cytokines: tumor necrosis factor-alpha (TNF-α), interferon gamma (IFNγ), interleukin 5 (IL- 5) and interleukin 10 (IL-10). At the end of the observation period it was observed a significant change in the electrocardiographic profile, autonomic and histopathological findings, suggestive of an inflammatory response with a shift of immune response towards the Th1 in Chg-NT animals compared to the other groups. It was observed that chronic treatment with anticholinesterase pyridostigmine bromide, in Chg-pyrido animals, caused a significant reduction in inflammatory immune response, myocardial fibrosis, without alteration of tissue and blood parasitism, suggesting a reduction in Th1 immune response without changing the Th2. This reduction in Th1 profile can be partly confirmed by a decrease in serum levels of IFNγ and tendency to decrease TNF-α, with no change in levels of IL-10, in Chg-pyrido animals when compared to NT-Chg group. In conclusion, our findings confirm the marked neuroimuno-modulatory role played by parasympathetic autonomic nervous system in the evolution of inflammatory-immune response to T. cruzi during the chronic Chagas' disease in experimental mice.eng
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dc.thumbnail.urlhttp://bdtd.uftm.edu.br/retrieve/2806/Dissert%20Marilia%20B%20Cuba.pdf.jpg*
dc.languageporpor
dc.publisherUniversidade Federal do Triângulo Mineiropor
dc.publisher.departmentInstituto de Ciências da Saúde - ICS::Curso de Medicinapor
dc.publisher.countryBrasilpor
dc.publisher.initialsUFTMpor
dc.publisher.programCurso de Pós-Graduação em Ciências Fisiológicaspor
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dc.rightsAcesso Abertopor
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/-
dc.subjectSistema nervoso autônomo parassimpáticopor
dc.subjectResposta imune.por
dc.subjectDoença de Chagas.por
dc.subjectParasympathetic autonomic nervous system.eng
dc.subjectImmune hagresponse.eng
dc.subjectChagas disease.eng
dc.subject.cnpqCiências Biológicaspor
dc.titleEfeitos da estimulação colinérgica com brometo de priridostigmina na cardiopatia chagásica crônica em camundongospor
dc.typeDissertaçãopor
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