Novo modelo de pancreatite crônica alcoólica em murinos: Aspectos inflamatórios, hiperalgesia visceral e fibrogênese

Detalhes bibliográficos
Ano de defesa: 2019
Autor(a) principal: Franco, Alvaro Xavier
Orientador(a): Souza, Marcellus Henrique Loiola Ponte de
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
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/47918
Resumo: Chronic pancreatitis (CP) is a progressive inflammatory disease characterized by irreversible morphological changes of the pancreas.The inflammatory process is persistent after deletion of deleterious factors and the pancreatic parenchyma is replaced by fibrous tissue, leading to loss of function.The characterization of a model of chronic alcoholic pancreatitis investigating the inflammatory aspects, hyperalgesia and fibrinogenesis, provides the understanding of its pathophysiology.Experimental chronic pancreatitis induced in Swiss mice, separated in control group and POA groups 1, 21, 29 and 44 days, with doses of palmitoleic acid (POA) associated to ethanol (1.35 g / kg) at concentrations of 150 , 75 and 37.5 mg / kg intraperitoneally with an interval of 1 (one) hour between the applications.The animals were euthanized and blood, faeces and pancreas were collected for biochemical analyzes (amylase, lipase, glucose, trypsin, MPO and α-SMA) and histopathology (glandular atrophy, fibrosis and monocellular cell infiltration).The survival of animals with experimental chronic pancreatitis was on average 56.06% and pancreatic tissue replacement was observed by fibrosis. There were alterations of important biochemical enzymes in lipase, glucose, trypsin, myeloperoxidase, Sudam III and presence of increased expression of α-SMA, a marker in the stellate cell that participate in the fibrosis process. Alterations in the nociceptive threshold were observed, persistent at the last experimental period. The application of POA associated with intraperitoneal ethanol consists of a new model with evidence of structural, biochemical and functional changes described in clinical practice, evidencing investigations and perspectives for studies of the pathophysiology of this disease, as well as new pharmacological modulation strategies.
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spelling Franco, Alvaro XavierSouza, Marcellus Henrique Loiola Ponte de2019-11-25T16:30:15Z2019-11-25T16:30:15Z2019-07-24FRANCO, A. X. Novo modelo de pancreatite crônica alcoólica em murinos: aspectos inflamatórios, hiperalgesia visceral e fibrogênese. 2019. 95 f. Tese (Doutorado em Ciências Médicas) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2019.http://www.repositorio.ufc.br/handle/riufc/47918Chronic pancreatitis (CP) is a progressive inflammatory disease characterized by irreversible morphological changes of the pancreas.The inflammatory process is persistent after deletion of deleterious factors and the pancreatic parenchyma is replaced by fibrous tissue, leading to loss of function.The characterization of a model of chronic alcoholic pancreatitis investigating the inflammatory aspects, hyperalgesia and fibrinogenesis, provides the understanding of its pathophysiology.Experimental chronic pancreatitis induced in Swiss mice, separated in control group and POA groups 1, 21, 29 and 44 days, with doses of palmitoleic acid (POA) associated to ethanol (1.35 g / kg) at concentrations of 150 , 75 and 37.5 mg / kg intraperitoneally with an interval of 1 (one) hour between the applications.The animals were euthanized and blood, faeces and pancreas were collected for biochemical analyzes (amylase, lipase, glucose, trypsin, MPO and α-SMA) and histopathology (glandular atrophy, fibrosis and monocellular cell infiltration).The survival of animals with experimental chronic pancreatitis was on average 56.06% and pancreatic tissue replacement was observed by fibrosis. There were alterations of important biochemical enzymes in lipase, glucose, trypsin, myeloperoxidase, Sudam III and presence of increased expression of α-SMA, a marker in the stellate cell that participate in the fibrosis process. Alterations in the nociceptive threshold were observed, persistent at the last experimental period. The application of POA associated with intraperitoneal ethanol consists of a new model with evidence of structural, biochemical and functional changes described in clinical practice, evidencing investigations and perspectives for studies of the pathophysiology of this disease, as well as new pharmacological modulation strategies.A pancreatite crônica (PC) é definida como uma doença inflamatória progressiva podendo levar a alterações morfológicas irreversíveis do pâncreas. O processo inflamatório é persistente mesmo após a supressão de fatores nocivos e o parênquima pancreático é substituído por tecido fibroso, podendo culminar na perda da função. A caracterização de um modelo de pancreatite crônica alcoólica investigando os aspectos inflamatórios, hiperalgesia e fibrinogênese, pode trazer um maior entendimento da sua fisiopatologia. APancreatite crônica experimental foi induzida emCamundongos Swiss, divididos aleatoriamente em grupo controle e grupos POA 1, 21, 29 e 44 dias, recebendo dose de ácido palmitoleico (POA) associado ao etanol (1,35 g/Kg) nas concentrações de 150, 75 e 37,5 mg/Kg via intraperitoneal com intervalo de 1 (uma) hora entre as aplicações. Os animais foram eutanasiados e foram coletados sangue, fezes e o pâncreas, para análises bioquímicas (amilase, lipase, glicose, tripsina, MPO e α-SMA) e histopatológica (atrofia glândular, fibrose e infiltrado de células monocelulares). A sobrevida dos animais com pancreatite crônica experimental foi em média de 56,06 % e foram percebidas substituição do tecido pancreático por fibrose. Observamos também, alterações bioquímicas importantes como na lipase, glicose, tripsina, mieloperoxidase, Sudam III e presença de expressão aumentada de α-SMA, sendo um marcador de células estrelares que participam do processo de fibrose. Alterações no limiar nociceptivo foram observadas, sendo persistente até o último período experimental. A aplicação de POA em associação com o etanol intraperitoneal consiste em um novo modelo com evidências de alterações estruturais, bioquímicas e funcionais descritas na prática clínica, abrindo novas investigações e perspectivas para estudos da fisiopatologia dessa doença, bem como de novas estratégias de modulação farmacológica.PancreatitePancreatite CrônicaHiperalgesiaFibroseNovo modelo de pancreatite crônica alcoólica em murinos: Aspectos inflamatórios, hiperalgesia visceral e fibrogêneseinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccessORIGINAL2019_tese_axfranco.pdf2019_tese_axfranco.pdfapplication/pdf1951532http://repositorio.ufc.br/bitstream/riufc/47918/3/2019_tese_axfranco.pdf72cc5a03d4419258c49d5172e73fc518MD53LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/47918/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52riufc/479182019-11-25 13:31:13.435oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2019-11-25T16:31:13Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Novo modelo de pancreatite crônica alcoólica em murinos: Aspectos inflamatórios, hiperalgesia visceral e fibrogênese
title Novo modelo de pancreatite crônica alcoólica em murinos: Aspectos inflamatórios, hiperalgesia visceral e fibrogênese
spellingShingle Novo modelo de pancreatite crônica alcoólica em murinos: Aspectos inflamatórios, hiperalgesia visceral e fibrogênese
Franco, Alvaro Xavier
Pancreatite
Pancreatite Crônica
Hiperalgesia
Fibrose
title_short Novo modelo de pancreatite crônica alcoólica em murinos: Aspectos inflamatórios, hiperalgesia visceral e fibrogênese
title_full Novo modelo de pancreatite crônica alcoólica em murinos: Aspectos inflamatórios, hiperalgesia visceral e fibrogênese
title_fullStr Novo modelo de pancreatite crônica alcoólica em murinos: Aspectos inflamatórios, hiperalgesia visceral e fibrogênese
title_full_unstemmed Novo modelo de pancreatite crônica alcoólica em murinos: Aspectos inflamatórios, hiperalgesia visceral e fibrogênese
title_sort Novo modelo de pancreatite crônica alcoólica em murinos: Aspectos inflamatórios, hiperalgesia visceral e fibrogênese
author Franco, Alvaro Xavier
author_facet Franco, Alvaro Xavier
author_role author
dc.contributor.author.fl_str_mv Franco, Alvaro Xavier
dc.contributor.advisor1.fl_str_mv Souza, Marcellus Henrique Loiola Ponte de
contributor_str_mv Souza, Marcellus Henrique Loiola Ponte de
dc.subject.por.fl_str_mv Pancreatite
Pancreatite Crônica
Hiperalgesia
Fibrose
topic Pancreatite
Pancreatite Crônica
Hiperalgesia
Fibrose
description Chronic pancreatitis (CP) is a progressive inflammatory disease characterized by irreversible morphological changes of the pancreas.The inflammatory process is persistent after deletion of deleterious factors and the pancreatic parenchyma is replaced by fibrous tissue, leading to loss of function.The characterization of a model of chronic alcoholic pancreatitis investigating the inflammatory aspects, hyperalgesia and fibrinogenesis, provides the understanding of its pathophysiology.Experimental chronic pancreatitis induced in Swiss mice, separated in control group and POA groups 1, 21, 29 and 44 days, with doses of palmitoleic acid (POA) associated to ethanol (1.35 g / kg) at concentrations of 150 , 75 and 37.5 mg / kg intraperitoneally with an interval of 1 (one) hour between the applications.The animals were euthanized and blood, faeces and pancreas were collected for biochemical analyzes (amylase, lipase, glucose, trypsin, MPO and α-SMA) and histopathology (glandular atrophy, fibrosis and monocellular cell infiltration).The survival of animals with experimental chronic pancreatitis was on average 56.06% and pancreatic tissue replacement was observed by fibrosis. There were alterations of important biochemical enzymes in lipase, glucose, trypsin, myeloperoxidase, Sudam III and presence of increased expression of α-SMA, a marker in the stellate cell that participate in the fibrosis process. Alterations in the nociceptive threshold were observed, persistent at the last experimental period. The application of POA associated with intraperitoneal ethanol consists of a new model with evidence of structural, biochemical and functional changes described in clinical practice, evidencing investigations and perspectives for studies of the pathophysiology of this disease, as well as new pharmacological modulation strategies.
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-11-25T16:30:15Z
dc.date.available.fl_str_mv 2019-11-25T16:30:15Z
dc.date.issued.fl_str_mv 2019-07-24
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
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dc.identifier.citation.fl_str_mv FRANCO, A. X. Novo modelo de pancreatite crônica alcoólica em murinos: aspectos inflamatórios, hiperalgesia visceral e fibrogênese. 2019. 95 f. Tese (Doutorado em Ciências Médicas) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2019.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/47918
identifier_str_mv FRANCO, A. X. Novo modelo de pancreatite crônica alcoólica em murinos: aspectos inflamatórios, hiperalgesia visceral e fibrogênese. 2019. 95 f. Tese (Doutorado em Ciências Médicas) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2019.
url http://www.repositorio.ufc.br/handle/riufc/47918
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