Influência do tratamento com abatacept no reparo de úlceras traumáticas em mucosa jugal de ratos

Detalhes bibliográficos
Autor(a) principal: Mesquita, Karine Cestaro
Data de Publicação: 2018
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
Texto Completo: http://www.repositorio.ufc.br/handle/riufc/30378
Resumo: Abatacept is known for the regulation of T cell activation and modulation of inflammatory cytokines, and due to this to mechanisms it may interferes on wound healing. The aim of this study was to evaluate the ulcer’s healing process on buccal mucosa of males Wistar rats administered with Abatacept subcutaneously. The rats were randomized between a control group, injected with saline subcutaneously, and other three study groups, administered with Abatacept subcutaneously in the doses of 3.2 (ABA 3.2), 8 (ABA 8) and 20 mg/kg/week (ABA 20). The administration of saline and Abatacept was performed 14 days before oral ulcer induction and continued until euthanasia, performed on days 1, 3, 7, 14 and 21 after the ulcer induction. Oral ulcers of 8 mm diameter and 2 mm deep were induced on the left buccal mucosa. Ulcer diameter, body mass variation, Picrosirius red, immunohistochemistry for iNOS, interleukin (IL) 1 beta, IL 6, IL 10, CD8 and CD30, vascular permeability and blood count were recorded. Histological slides were performed for histopathological (scores) and histomorphometric analysis, such as: polymorphonuclear, mononuclear, angiogenesis and fibroplasia. ANOVA-1-way and -2-way/Bonferroni and Kruskal-Wallis/Dunn were used in the statistical analysis (GraphPad Prism 5.0®, p<0.05). Abatacept administration decreased ulcer diameter (p<0.001), polymorphonuclear (p<0.001) and mononuclear count (p=0.027), CD8+/CD30+ relation (p<0.001) and vascular permeability (p<0.001). However, the collagenesis (p<0.001) and IL-10 expression levels (p=0.016) increased on days 3 and 7. In the ABA 20 group, the over Abatacept doses were related to late wound healing (p<0.001), reduced angiogenesis (p=0.017) and extended period of high levels of iNOS (p=0.026), IL 1 beta (p=0.007) and IL 6 (p<0.001). This study demonstrated that Abatacept accelerates ulcer healing on the buccal mucosa of male Wistar rats due to the reduced migration of inflammatory cells, meanwhile, higher doses were associated with delayed repair and extended expression of proinflammatory cytokines.
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spelling Influência do tratamento com abatacept no reparo de úlceras traumáticas em mucosa jugal de ratosInfluence of treatment with abatacept on the repair of traumatic ulcers in jugal mucosa of ratsAbatacepteÚlceras OraisLinfócitos TCicatrizaçãoAbatacept is known for the regulation of T cell activation and modulation of inflammatory cytokines, and due to this to mechanisms it may interferes on wound healing. The aim of this study was to evaluate the ulcer’s healing process on buccal mucosa of males Wistar rats administered with Abatacept subcutaneously. The rats were randomized between a control group, injected with saline subcutaneously, and other three study groups, administered with Abatacept subcutaneously in the doses of 3.2 (ABA 3.2), 8 (ABA 8) and 20 mg/kg/week (ABA 20). The administration of saline and Abatacept was performed 14 days before oral ulcer induction and continued until euthanasia, performed on days 1, 3, 7, 14 and 21 after the ulcer induction. Oral ulcers of 8 mm diameter and 2 mm deep were induced on the left buccal mucosa. Ulcer diameter, body mass variation, Picrosirius red, immunohistochemistry for iNOS, interleukin (IL) 1 beta, IL 6, IL 10, CD8 and CD30, vascular permeability and blood count were recorded. Histological slides were performed for histopathological (scores) and histomorphometric analysis, such as: polymorphonuclear, mononuclear, angiogenesis and fibroplasia. ANOVA-1-way and -2-way/Bonferroni and Kruskal-Wallis/Dunn were used in the statistical analysis (GraphPad Prism 5.0®, p<0.05). Abatacept administration decreased ulcer diameter (p<0.001), polymorphonuclear (p<0.001) and mononuclear count (p=0.027), CD8+/CD30+ relation (p<0.001) and vascular permeability (p<0.001). However, the collagenesis (p<0.001) and IL-10 expression levels (p=0.016) increased on days 3 and 7. In the ABA 20 group, the over Abatacept doses were related to late wound healing (p<0.001), reduced angiogenesis (p=0.017) and extended period of high levels of iNOS (p=0.026), IL 1 beta (p=0.007) and IL 6 (p<0.001). This study demonstrated that Abatacept accelerates ulcer healing on the buccal mucosa of male Wistar rats due to the reduced migration of inflammatory cells, meanwhile, higher doses were associated with delayed repair and extended expression of proinflammatory cytokines.O Abatacept regula a ativação dos Linfócitos T (LT) e modula a liberação de citocinas, podendo interferir no mecanismo de cicatrização. O presente trabalho visou avaliar o processo cicatricial de úlceras em mucosa jugal de ratos Wistar em tratamento com Abatacept. Os ratos foram distribuídos aleatoriamente em quatro grupos, sendo um controle tratado com solução salina subcutânea, e três grupos tratados com Abatacept por administração subcutânea nas doses 3,2 (ABA 3,2), 8 (ABA 8) e 20 (ABA 20) mg/kg/semana. A administração de solução salina e abatacept foi iniciada 14 dias antes da confecção da úlcera e continuada até o final a eutanásia, realizada nos dias 1, 3, 7, 14 e 21 após a indução da úlcera. As úlceras orais foram induzidas na mucosa jugal direita com punch dermatológico de 8mm de diâmetro e 2mm de profundidade. Mensurou-se o diâmetro da úlcera, variação ponderal e foram confeccionadas lâminas para análise histopatológicas (escores) e histomorfométrica (contagem de polimorfonucleares, mononucleares, vasos e fibroblastos/miofibroblastos). Foi realizada coloração de Picrosirius Red para análise da colagênese e imuno-histoquímica para óxido nítrico sintase induzida (iNOS), Interleucina(IL)-1beta(1β), -6, -10, CD8 e CD30. O experimento foi repetido para realização de ensaio de permeabilidade vascular e hemograma. ANOVA-1-way e -2-way/Bonferroni e Kruskal-Wallis/Dunn foram utilizados para análise estatística (GraphPad Prism 5.0®, p<0,05). O tratamento com Abatacept reduziu o diâmetro da úlcera (p<0,001), o número de polimorfonucleares (p<0,001) e mononucleares (p=0,027), a relação CD8+/CD30+ (p<0,001) e a permeabilidade vascular (p<0,001), e aumentou a colagênese (p<0,001) e a expressão de IL-10 (p=0,016) no início do protocolo. Porém, na maior dose (ABA 20) houve retardo do reparo (p<0,001) do número de vasos (p=0,017), redução de fibroblastos/miofibroblastos (p<0,001), além de prolongamento da expressão de iNOS (p=0,026), IL-1β (p=0,007) e IL-6 (p<0,001). Conclui-se que o abatacept acelera a cicatrização de úlceras orais através de redução da migração de células inflamatórias, mas a sobredose leva ao retardo do reparo e prolongamento da expressão de citocinas pró-inflamatórias.Sousa, Fabrício BituMesquita, Karine Cestaro2018-03-15T16:40:37Z2018-03-15T16:40:37Z2018-02-05info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfMESQUITA, K. C. Influência do tratamento com abatacept no reparo de úlceras traumáticas em mucosa jugal de ratos. 2018. 55 f. Dissertação (Mestrado em Odontologia) - Faculdade de Farmácia, Odontologia e Enfermagem. Universidade Federal do Ceará. Fortaleza, 2018.http://www.repositorio.ufc.br/handle/riufc/30378porreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccess2019-01-31T18:28:20Zoai:repositorio.ufc.br:riufc/30378Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2024-09-11T18:17:48.859031Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.none.fl_str_mv Influência do tratamento com abatacept no reparo de úlceras traumáticas em mucosa jugal de ratos
Influence of treatment with abatacept on the repair of traumatic ulcers in jugal mucosa of rats
title Influência do tratamento com abatacept no reparo de úlceras traumáticas em mucosa jugal de ratos
spellingShingle Influência do tratamento com abatacept no reparo de úlceras traumáticas em mucosa jugal de ratos
Mesquita, Karine Cestaro
Abatacepte
Úlceras Orais
Linfócitos T
Cicatrização
title_short Influência do tratamento com abatacept no reparo de úlceras traumáticas em mucosa jugal de ratos
title_full Influência do tratamento com abatacept no reparo de úlceras traumáticas em mucosa jugal de ratos
title_fullStr Influência do tratamento com abatacept no reparo de úlceras traumáticas em mucosa jugal de ratos
title_full_unstemmed Influência do tratamento com abatacept no reparo de úlceras traumáticas em mucosa jugal de ratos
title_sort Influência do tratamento com abatacept no reparo de úlceras traumáticas em mucosa jugal de ratos
author Mesquita, Karine Cestaro
author_facet Mesquita, Karine Cestaro
author_role author
dc.contributor.none.fl_str_mv Sousa, Fabrício Bitu
dc.contributor.author.fl_str_mv Mesquita, Karine Cestaro
dc.subject.por.fl_str_mv Abatacepte
Úlceras Orais
Linfócitos T
Cicatrização
topic Abatacepte
Úlceras Orais
Linfócitos T
Cicatrização
description Abatacept is known for the regulation of T cell activation and modulation of inflammatory cytokines, and due to this to mechanisms it may interferes on wound healing. The aim of this study was to evaluate the ulcer’s healing process on buccal mucosa of males Wistar rats administered with Abatacept subcutaneously. The rats were randomized between a control group, injected with saline subcutaneously, and other three study groups, administered with Abatacept subcutaneously in the doses of 3.2 (ABA 3.2), 8 (ABA 8) and 20 mg/kg/week (ABA 20). The administration of saline and Abatacept was performed 14 days before oral ulcer induction and continued until euthanasia, performed on days 1, 3, 7, 14 and 21 after the ulcer induction. Oral ulcers of 8 mm diameter and 2 mm deep were induced on the left buccal mucosa. Ulcer diameter, body mass variation, Picrosirius red, immunohistochemistry for iNOS, interleukin (IL) 1 beta, IL 6, IL 10, CD8 and CD30, vascular permeability and blood count were recorded. Histological slides were performed for histopathological (scores) and histomorphometric analysis, such as: polymorphonuclear, mononuclear, angiogenesis and fibroplasia. ANOVA-1-way and -2-way/Bonferroni and Kruskal-Wallis/Dunn were used in the statistical analysis (GraphPad Prism 5.0®, p<0.05). Abatacept administration decreased ulcer diameter (p<0.001), polymorphonuclear (p<0.001) and mononuclear count (p=0.027), CD8+/CD30+ relation (p<0.001) and vascular permeability (p<0.001). However, the collagenesis (p<0.001) and IL-10 expression levels (p=0.016) increased on days 3 and 7. In the ABA 20 group, the over Abatacept doses were related to late wound healing (p<0.001), reduced angiogenesis (p=0.017) and extended period of high levels of iNOS (p=0.026), IL 1 beta (p=0.007) and IL 6 (p<0.001). This study demonstrated that Abatacept accelerates ulcer healing on the buccal mucosa of male Wistar rats due to the reduced migration of inflammatory cells, meanwhile, higher doses were associated with delayed repair and extended expression of proinflammatory cytokines.
publishDate 2018
dc.date.none.fl_str_mv 2018-03-15T16:40:37Z
2018-03-15T16:40:37Z
2018-02-05
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv MESQUITA, K. C. Influência do tratamento com abatacept no reparo de úlceras traumáticas em mucosa jugal de ratos. 2018. 55 f. Dissertação (Mestrado em Odontologia) - Faculdade de Farmácia, Odontologia e Enfermagem. Universidade Federal do Ceará. Fortaleza, 2018.
http://www.repositorio.ufc.br/handle/riufc/30378
identifier_str_mv MESQUITA, K. C. Influência do tratamento com abatacept no reparo de úlceras traumáticas em mucosa jugal de ratos. 2018. 55 f. Dissertação (Mestrado em Odontologia) - Faculdade de Farmácia, Odontologia e Enfermagem. Universidade Federal do Ceará. Fortaleza, 2018.
url http://www.repositorio.ufc.br/handle/riufc/30378
dc.language.iso.fl_str_mv por
language por
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dc.source.none.fl_str_mv reponame:Repositório Institucional da Universidade Federal do Ceará (UFC)
instname:Universidade Federal do Ceará (UFC)
instacron:UFC
instname_str Universidade Federal do Ceará (UFC)
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institution UFC
reponame_str Repositório Institucional da Universidade Federal do Ceará (UFC)
collection Repositório Institucional da Universidade Federal do Ceará (UFC)
repository.name.fl_str_mv Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)
repository.mail.fl_str_mv bu@ufc.br || repositorio@ufc.br
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