Desenvolvimento de modelo experimental de refluxo gastresofágico não erosivo em ratos e suas repercussões na contratilidade esofagiana

Detalhes bibliográficos
Ano de defesa: 2017
Autor(a) principal: Gadelha, Kalinne Kelly Lima
Orientador(a): Magalhães, Pedro Jorge Caldas
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/24506
Resumo: Esophageal motor abnormalities, as well defects in the lower esophageal sphincter, are common aspects of gastroesophageal reflux disease. The objective of this work is to develop a model of non-erosive gastroesophageal reflux in rats by acute exposure of the esophagus to solutions that simulate gastric content and evaluate the repercussions on contractility through isometric recordings obtained from esophagus and gastroesophageal junction (GEJ) samples by a digital acquisition system. Esophageal segments mounted in the circular direction that remained for 30 min in contact with Tyrode pH 1 containig pepsin and taurodeoxycholate (TDCA) showed lower contractile responses to increasing concentrations of KCl, CCh and EFS (Electric Field Stimulation) when compared to segments exposed to the control solution (Tyrode pH 7.4), while longitudinal segments showed hiporesponsiveness only for the cholinergic stimulus. Initial minutes, of the evaluation of the esophageal mucosa revealed a decrease in the transepithelial electrical resistance (TER) of segments exposed to the same acid challenge in comparison to the control solution. The circular esophagus in contact for 10 min with the acidic solution showed lower values of contractions evoked by KCl, CCh and EFS when compared to the control exposure, whereas longitudinal esophageal strips did not present significant alterations. The contractile evaluation performed on GEJ rings did not show significant differences in responses to KCl, CCh or EFS stimuli when we varied both the pH and time between the groups. Experimental protocols revealed similarities in the relaxant response in tissues exposed to the control or acid solution caused by increasing concentrations of sodium nitroprusside, isoproterenol or serotonin in the esophagus preparations, whereas segments of GEJ relaxed more when previous exposed to acid contact. The topical application of alginate suspension in esophageal mucosa samples was able to improve TER damage caused by exposure to acidic challenge. The contractility of esophageal muscle samples was also improved, but the responsiveness of GEJ segments was lower with previous application of the formulation. Esophagus filled only with acidic solution (pH 1) for 30 min had no significant change in the contractile response induced by EFS, an effect observed only with the combination of this solution with pepsin and TDCA. The present model reveals motor alterations of the esophagus and GEJ of rats compatible with phenomena already seen in more aggressive models and allows other important investigations for the disease.
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spelling Gadelha, Kalinne Kelly LimaMagalhães, Pedro Jorge Caldas2017-08-02T12:29:08Z2017-08-02T12:29:08Z2017-07-04GADELHA, K. K. L. Desenvolvimento de modelo experimental de refluxo gastresofágico não erosivo em ratos e suas repercussões na contratilidade esofagiana. 2017. 77 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2017.http://www.repositorio.ufc.br/handle/riufc/24506Esophageal motor abnormalities, as well defects in the lower esophageal sphincter, are common aspects of gastroesophageal reflux disease. The objective of this work is to develop a model of non-erosive gastroesophageal reflux in rats by acute exposure of the esophagus to solutions that simulate gastric content and evaluate the repercussions on contractility through isometric recordings obtained from esophagus and gastroesophageal junction (GEJ) samples by a digital acquisition system. Esophageal segments mounted in the circular direction that remained for 30 min in contact with Tyrode pH 1 containig pepsin and taurodeoxycholate (TDCA) showed lower contractile responses to increasing concentrations of KCl, CCh and EFS (Electric Field Stimulation) when compared to segments exposed to the control solution (Tyrode pH 7.4), while longitudinal segments showed hiporesponsiveness only for the cholinergic stimulus. Initial minutes, of the evaluation of the esophageal mucosa revealed a decrease in the transepithelial electrical resistance (TER) of segments exposed to the same acid challenge in comparison to the control solution. The circular esophagus in contact for 10 min with the acidic solution showed lower values of contractions evoked by KCl, CCh and EFS when compared to the control exposure, whereas longitudinal esophageal strips did not present significant alterations. The contractile evaluation performed on GEJ rings did not show significant differences in responses to KCl, CCh or EFS stimuli when we varied both the pH and time between the groups. Experimental protocols revealed similarities in the relaxant response in tissues exposed to the control or acid solution caused by increasing concentrations of sodium nitroprusside, isoproterenol or serotonin in the esophagus preparations, whereas segments of GEJ relaxed more when previous exposed to acid contact. The topical application of alginate suspension in esophageal mucosa samples was able to improve TER damage caused by exposure to acidic challenge. The contractility of esophageal muscle samples was also improved, but the responsiveness of GEJ segments was lower with previous application of the formulation. Esophagus filled only with acidic solution (pH 1) for 30 min had no significant change in the contractile response induced by EFS, an effect observed only with the combination of this solution with pepsin and TDCA. The present model reveals motor alterations of the esophagus and GEJ of rats compatible with phenomena already seen in more aggressive models and allows other important investigations for the disease.Anormalidades motoras esofágicas, assim como defeitos no esfíncter esofágico inferior, são achados frequentes na doença do refluxo gastroesofágico. O objetivo deste trabalho foi desenvolver um modelo de refluxo gastresofágico não erosivo em ratos pela exposição aguda do esôfago a soluções que simulem o conteúdo gástrico e avaliar suas repercussões na contratilidade, através de registros isométricos obtidos de amostras de esôfago e de junção esôfago-gástrica (JEG) por sistema de aquisição de dados. Segmentos de esôfago montados no sentido circular que permaneceram 30 min em contato com solução de Tyrode pH 1 enriquecida com pepsina e taurodeoxicolato (TDCA) mostraram menores respostas contráteis a concentrações crescentes de KCl, CCh e estimulação por campo elétrico (EFS) se comparadas a segmentos expostos a solução controle (Tyrode pH 7,4), enquanto segmentos longitudinais foram hiporresponivos apenas ao estimulo colinérgico. A avaliação da mucosa esofágica revelou, já nos primeiros minutos, decréscimo na resistência elétrica transepitelial (RET) de segmentos expostos ao mesmo desafio ácido em comparação à solução controle, diminuição esta inexpressiva em pH fracamente ácido (4,0). Já esôfago circular em contato por 10 min com a solução ácida mostrou menores valores de contrações evocadas por KCl, CCh e EFS quando comparado à exposição controle, enquanto tiras esofágicas longitudinais não apresentaram alterações significativas. A avaliação contrátil feita em segmentos de JEG não mostrou diferenças significativas nas respostas aos estímulos por KCl, CCh ou EFS quando variamos tanto o pH como o tempo entre os grupos. Protocolos experimentais revelaram similaridades na resposta relaxante em tecidos expostos à solução controle ou ácida causadas por concentrações crescentes de nitroprussiato de sódio, isoproterenol ou serotonina nas preparações de esôfago, enquanto segmentos de JEG relaxaram mais quando submetidos previamente ao contato ácido. A aplicação tópica de suspensão de alginato em amostras de mucosa esofágica foi capaz de melhorar o prejuízo na RET causado pela exposição ao desafio ácido. A contratilidade de amostras musculares esofágicas também foi melhorada, porém a responsividade de segmentos de JEG foi menor com a aplicação prévia da formulação. Esôfagos preenchidos apenas com solução acidificada (pH 1) durante 30 min não tiveram mudança significativa na resposta contrátil induzida por EFS, efeito observado apenas com a combinação dessa solução com pepsina e TDCA. O presente modelo revela alterações motoras de esôfago e JEG de ratos compatíveis com fenômenos já vistos em modelos mais agressivos e permite outras investigações importantes para a doença.Refluxo GastroesofágicoContração MiocárdicaMucosa EsofágicaRatosDesenvolvimento de modelo experimental de refluxo gastresofágico não erosivo em ratos e suas repercussões na contratilidade esofagianaDevelopment of an experimental model of non erosive gastroesofagic reflux in rats and their repercussions in esofagian contractilityinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccessORIGINAL2017_dis_kklgadelha.pdf2017_dis_kklgadelha.pdfapplication/pdf3515465http://repositorio.ufc.br/bitstream/riufc/24506/1/2017_dis_kklgadelha.pdf91db56f48a2af979e55f7a8576e951e1MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/24506/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52riufc/245062019-10-17 11:05:06.25oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2019-10-17T14:05:06Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Desenvolvimento de modelo experimental de refluxo gastresofágico não erosivo em ratos e suas repercussões na contratilidade esofagiana
dc.title.en.pt_BR.fl_str_mv Development of an experimental model of non erosive gastroesofagic reflux in rats and their repercussions in esofagian contractility
title Desenvolvimento de modelo experimental de refluxo gastresofágico não erosivo em ratos e suas repercussões na contratilidade esofagiana
spellingShingle Desenvolvimento de modelo experimental de refluxo gastresofágico não erosivo em ratos e suas repercussões na contratilidade esofagiana
Gadelha, Kalinne Kelly Lima
Refluxo Gastroesofágico
Contração Miocárdica
Mucosa Esofágica
Ratos
title_short Desenvolvimento de modelo experimental de refluxo gastresofágico não erosivo em ratos e suas repercussões na contratilidade esofagiana
title_full Desenvolvimento de modelo experimental de refluxo gastresofágico não erosivo em ratos e suas repercussões na contratilidade esofagiana
title_fullStr Desenvolvimento de modelo experimental de refluxo gastresofágico não erosivo em ratos e suas repercussões na contratilidade esofagiana
title_full_unstemmed Desenvolvimento de modelo experimental de refluxo gastresofágico não erosivo em ratos e suas repercussões na contratilidade esofagiana
title_sort Desenvolvimento de modelo experimental de refluxo gastresofágico não erosivo em ratos e suas repercussões na contratilidade esofagiana
author Gadelha, Kalinne Kelly Lima
author_facet Gadelha, Kalinne Kelly Lima
author_role author
dc.contributor.author.fl_str_mv Gadelha, Kalinne Kelly Lima
dc.contributor.advisor1.fl_str_mv Magalhães, Pedro Jorge Caldas
contributor_str_mv Magalhães, Pedro Jorge Caldas
dc.subject.por.fl_str_mv Refluxo Gastroesofágico
Contração Miocárdica
Mucosa Esofágica
Ratos
topic Refluxo Gastroesofágico
Contração Miocárdica
Mucosa Esofágica
Ratos
description Esophageal motor abnormalities, as well defects in the lower esophageal sphincter, are common aspects of gastroesophageal reflux disease. The objective of this work is to develop a model of non-erosive gastroesophageal reflux in rats by acute exposure of the esophagus to solutions that simulate gastric content and evaluate the repercussions on contractility through isometric recordings obtained from esophagus and gastroesophageal junction (GEJ) samples by a digital acquisition system. Esophageal segments mounted in the circular direction that remained for 30 min in contact with Tyrode pH 1 containig pepsin and taurodeoxycholate (TDCA) showed lower contractile responses to increasing concentrations of KCl, CCh and EFS (Electric Field Stimulation) when compared to segments exposed to the control solution (Tyrode pH 7.4), while longitudinal segments showed hiporesponsiveness only for the cholinergic stimulus. Initial minutes, of the evaluation of the esophageal mucosa revealed a decrease in the transepithelial electrical resistance (TER) of segments exposed to the same acid challenge in comparison to the control solution. The circular esophagus in contact for 10 min with the acidic solution showed lower values of contractions evoked by KCl, CCh and EFS when compared to the control exposure, whereas longitudinal esophageal strips did not present significant alterations. The contractile evaluation performed on GEJ rings did not show significant differences in responses to KCl, CCh or EFS stimuli when we varied both the pH and time between the groups. Experimental protocols revealed similarities in the relaxant response in tissues exposed to the control or acid solution caused by increasing concentrations of sodium nitroprusside, isoproterenol or serotonin in the esophagus preparations, whereas segments of GEJ relaxed more when previous exposed to acid contact. The topical application of alginate suspension in esophageal mucosa samples was able to improve TER damage caused by exposure to acidic challenge. The contractility of esophageal muscle samples was also improved, but the responsiveness of GEJ segments was lower with previous application of the formulation. Esophagus filled only with acidic solution (pH 1) for 30 min had no significant change in the contractile response induced by EFS, an effect observed only with the combination of this solution with pepsin and TDCA. The present model reveals motor alterations of the esophagus and GEJ of rats compatible with phenomena already seen in more aggressive models and allows other important investigations for the disease.
publishDate 2017
dc.date.accessioned.fl_str_mv 2017-08-02T12:29:08Z
dc.date.available.fl_str_mv 2017-08-02T12:29:08Z
dc.date.issued.fl_str_mv 2017-07-04
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
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dc.identifier.citation.fl_str_mv GADELHA, K. K. L. Desenvolvimento de modelo experimental de refluxo gastresofágico não erosivo em ratos e suas repercussões na contratilidade esofagiana. 2017. 77 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2017.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/24506
identifier_str_mv GADELHA, K. K. L. Desenvolvimento de modelo experimental de refluxo gastresofágico não erosivo em ratos e suas repercussões na contratilidade esofagiana. 2017. 77 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2017.
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