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Título da fonte: Biblioteca Digital de Teses e Dissertações da UFTM
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spelling Arginase-1 e perfil treg parecem modular processo inflamatório em pacientes com gastrite crônica e IL-33 pode ser a citocina de alarme nos pacientes H.pylori positivoHelicobacter pylori.Gastrites.Arginase-1.TGF-β.FOXP3.Treg.IL-33.Helicobacter pylori.Gastritis.Arginase-1.TGF-β.FOXP3.Treg.IL-33.Ciências da SaúdeMedicinaINTRODUÇÃO: Helicobacter pylori (H. pylori) é uma bactéria altamente prevalente em nosso meio e está diretamente envolvida em várias doenças do trato digestivo superior como gastrite, úlcera péptica e câncer gástrico. Neste estudo foram pesquisados dados preditivos do ponto de vista clínico, endoscópico, anatomopatológico bem como os mecanismos da resposta imune frente à presença desta bactéria Várias moléculas ativadoras do sistema imune têm sido descritas e estudadas na tentativa de conter a infecção pelo H pylori. OBJETIVOS: Estudar a presença de infecção por H. pylori na mucosa gástrica com a história clínica, antecedentes clínicos, doenças concomitantes, dados no exame de endoscopia digestiva alta (EDA) do exame anatomopatológico (EAP). Na resposta imune, analisar nos fragmentos do corpo gástrico por qPCR, a expressão mRNA das citocinas IFN- , IL-17, IL-10, TGF- , IL-6, IL-22, IL-23, IL-33; dos fatores de transcrição T-bet, ROR t e FOXP3; das enzimas ARG1, ARG2 e NOS2; dos neuropeptídeos VIP e TAC, e seus respectivos receptores VIP-R1 e TAC-R1. Comparar a expressão desses genes com a presença ou ausência da bactéria H. pylori. MATERIAL E MÉTODOS: foram avaliados 126 pacientes que apresentavam sintomas do trato digestivo superior e com indicação clínica de exame de Endoscopia Digestiva Alta (EDA). Antes da realização do exame de endoscopia digestiva alta foi feito um questionário clínico detalhado e durante o exame endoscópico realizaram-se biópsias múltiplas do esôfago, corpo e antro gástrico e teste rápido da urease. Fragmentos da mucosa do corpo e do antro gástrico foram coletados para o exame anatomopatológico e para análise da expressão das enzimas, citocinas e fatores de transcrição por meio de PCR em tempo real, qPCR. RESULTADOS: Não foi encontrado nenhum dado clínico que pudesse estar relacionado à presença da infecção do H. pylori no estômago. Os achados endoscópicos que tiveram relevância com a presença da bactéria foi a gastrite tanto no antro como no corpo gástrico (p<0,05). No exame anatomopatológico (EAP) os pacientes que usaram Inibidores de Bomba de Prótons (IBP) apresentaram uma diminuição da positividade da bactéria no antro e no corpo gástrico (p<0,05). A presença da gastrite no corpo gástrico ou antro gástrico teve significância com a positividade da bactéria (p<0,05). A expressão do gene ARG1 foi significativamente maior no grupo de pacientes com gastrite crônica sem atividade quando comparada ao grupo controle (Kruskal Wallis; p=0.02). A expressão do gene do TGF- e seu fator de transcrição FOXP3 foram significativamente maiores no grupo de pacientes com gastrite crônica sem atividade, quando comparada ao grupo controle. Ao comparar a expressão dos genes IFN- , IL-17, IL-10 e TGF- e os fatores de transcrição T-bet e ROR, com a presença ou ausência do H.pylori, não houve diferença significativa. No entanto, a expressão do FOXP3 foi significativamente menor nos pacientes H. pylori positivo quando comparado com os pacientes H. pylori negativos (Mann-Whitney; p=0.01). CONCLUSÕES: Infecção por H. pylori não mostrou nenhum fator clínico preditivo da sua presença. Na EDA destacou-se a presença da gastrite no antro como dado de provável infecção da bactéria. O uso de IBPs deverá ser suspenso por pelo menos duas semanas antes da EDA para evitarmos falsos negativos da presença do H. pylori no estômago. O EAP mostrou-se necessário para classificar os diferentes tipos gastrites e/ou alterações histopatológicas provocadas pela bactéria. ARG-1 e perfil Treg parecem estar modulando o processo inflamatório, protegendo esses pacientes de lesões teciduais com gastrite crônica sem atividade. Ainda, sugerimos que a IL-33 pode ser um mediador crucial da resposta imune à infecção após dano na mucosa gástrica.INTRODUCTION: Helicobacter pylori (H. pylori) is a highly prevalent bacterium in our midst and is directly involved in several diseases of the upper digestive tract such as gastritis, peptic ulcer and gastric cancer. In this study, predictive data from the clinical, endoscopic, anatomopathological and immune response mechanisms were investigated against the presence of this bacterium. Immune activating molecules have been described and studied in an attempt to contain H pylori infection. OBJECTIVES: to study the presence of H. pylori infection in the gastric mucosa with the clinical history, medical history, concomitant diseases, and data from the upper digestive endoscopy (UDE) examination of the anatomopathological examination (APE). At imune response, analyse fragments of the gastric body by qPCR, mRNA expression of IFNcytokines, IL-17, IL-10, TGF  , IL-6, IL-22, IL-23, IL-33; of the transcription factors T-bet , ROR  t and FOXP3 ; of the enzymes ARG1, ARG2 and NOS2 ; of the neuropeptides VIP and TAC, and their respective receptors VIPR1, and TAC-R1 . To compare the expression of these genes with the presence or absence of H. pylori bacteria . MATERIAL AND METHODS: were evaluated 126 patients with symptoms of the upper digestive tract and with a clinical indication of Digestive High Endoscopy (UDE) . Before the endoscopy examination a detailed clinical questionnaire was perforemed and during the examination was performed multiple biopsies of the esophagus, gastric body and antrum and rapid urease test. Fragments of the mucosa of the body and the gastric antrum were collected for anatomopathological examination and for analysis of the expression of enzymes, cytokines and transcription factors by real-time PCR , qPCR . RESULTS: no clinical data were found that could be related to the presence of H. pylori infection in the stomach. Endoscopic findings that have relevance to the presence of bacteria was gastritis in both antrum and in the gastric corpus (p<0.05). Patients who used Proton Pump Inhibitors (PPIs) showed a decrease in the positivity of the bacteria in the antrum and in the gastric body (p<0.05) through the APE. The presence of gastritis in the gastric body or gastric antrum was significant with the positivity of the bacterium (p<0,05). The expression of the ARG1 gene was significantly higher in the group of patients with chronic gastritis with no activity when compared to the control group (Kruskal Wallis; p = 0.02). The gene expression of TGF  gene and its transcription factor FOXP3 were significantly higher in the group of chronic no-active gastrites pacientes when compared to the control group. When comparing the expression of IFN  IL-17, IL-10 and TGF  genes and the T-bet and ROR   transcription factors , with the presence or absence of H. pylori , there was no significant difference . However, FOXP3 expression was significantly lower in H. pylori positive patients when compared to H. pylori negative patients (Mann-Whitney, p=0.01). CONCLUSIONS: H. pylori infection showed no clinical factor predictive of their presence. In the UDE, the presence of gastritis in the antrum was highlighted as a probable infection of the bacterium. The use of PPIs should be discontinued for at least two weeks prior to UDE to avoid false negatives of the presence of H. pylori in the stomach. PAD was necessary to classify the differet types of gastritis and/or histopathological changes caused by the bacteria . ARG-1 and Treg profile appear to be modulating the inflammatory process, protecting these patients from tissue lesions with chronic gastritis without activity . Furthermore, we suggest that IL-33 may be a crucial mediator of the immune response to infection after gastric mucosal damage.Universidade Federal do Triângulo MineiroInstituto de Ciências da Saúde - ICS::Programa de Pós-Graduação em Ciências da SaúdeBrasilUFTMPrograma de Pós-Graduação em Ciências da SaúdeRODRIGUES, Denise Bertulucci Rocha10676897886http://lattes.cnpq.br/5953745136489913RODRIGUES JUNIOR, Virmondes45813493620http://lattes.cnpq.br/8909243237236516SILVA, Emerson Abdulmassih Wood da2022-07-25T17:39:44Z2018-12-112022-07-25T17:39:44Z2018-12-11info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfSILVA, Emerson Abdulmassih Wood da. Arginase-1 e perfil treg parecem modular processo inflamatório em pacientes com gastrite crônica e IL-33 pode ser a citocina de alarme nos pacientes H.pylori positivo. 2018. . 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