Efeitos da deficiência de vitamina D na função pulmonar de um modelo de asma alérgica experimental

Detalhes bibliográficos
Autor(a) principal: Nuñez, Nailê Karine
Data de Publicação: 2017
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da PUC_RS
Texto Completo: http://tede2.pucrs.br/tede2/handle/tede/7857
Resumo: Background: Asthma is a chronic disease of the airways, characterized by bronchial inflammation and hyperresponsiveness, which affects approximately 300 million people around the world. The increase in the prevalence of asthma in recent years has been associated with an increase in vitamin D deficiency. About 1 billion people in the world have insufficient levels of vitamin D due to many factors such as reduced outdoor activities, sunscreens use and a diet low in vitamin D. In addition, many studies suggest that vitamin D deficiency has a direct effect on lung function, leading to changes in the structure of the airways and in the inflammatory process. Objectives: To evaluate the effect of vitamin D deficiency at different life stages in a murine model of allergic airways disease house dust mite (HDM) induced on inflammation and lung function. Methods: Female BALB / c mice were placed in a diet replete or deficient in vitamin D at three-week old. At 8 weeks, females were mated with males on a diet replete in vitamin D. At birth, pups were cross-fostered to assess the effects of vitamin D deficiency at different stages of life, in utero (Vit D -/+), postnatal (Vit D +/-) and whole-life (Vit D - / -) compared to the control group whole-life vitamin D replete (Vit D + / +). At 8 weeks of age, mice of both sexes were challenged for 10 consecutive days intranasally with either HDM extract or saline solution after mild anesthesia. The animals were anesthetized for lung function test and then submitted to euthanasia for bronchoalveolar lavage (BAL) and lung tissue removal 24 hours after the last intranasal challenge. The total BAL cell count and collagen quantification of lung tissue homogenized were evaluated. Results: Vitamin D deficiency did not affect HDM-induced inflammation, which was characterized by BAL eosinophilia. Vitamin D deficiency at any life stage (in utero, postnatal and all life) caused impairment of lung function, increased tissue damping and tissue elastance, being particularly observed in females. On the other hand, the asthma HDM-induced decreased airway distensibility, but only in females and vitamin D do not altered this response. Conclusion: Our results suggest that vitamin D and HDM have different mechanisms that influence in the development of allergic lung disease and furthermore the effects appear to be sex-specific.
id P_RS_a8f4dfefb2723755d7a00beca484f329
oai_identifier_str oai:tede2.pucrs.br:tede/7857
network_acronym_str P_RS
network_name_str Biblioteca Digital de Teses e Dissertações da PUC_RS
repository_id_str
spelling Pitrez, Paulo Márcio Condessahttp://lattes.cnpq.br/6731821353792634Zosky, Graeme R.http://lattes.cnpq.br/4602172317517240Nuñez, Nailê Karine2018-02-23T16:35:09Z2017-07-12http://tede2.pucrs.br/tede2/handle/tede/7857Background: Asthma is a chronic disease of the airways, characterized by bronchial inflammation and hyperresponsiveness, which affects approximately 300 million people around the world. The increase in the prevalence of asthma in recent years has been associated with an increase in vitamin D deficiency. About 1 billion people in the world have insufficient levels of vitamin D due to many factors such as reduced outdoor activities, sunscreens use and a diet low in vitamin D. In addition, many studies suggest that vitamin D deficiency has a direct effect on lung function, leading to changes in the structure of the airways and in the inflammatory process. Objectives: To evaluate the effect of vitamin D deficiency at different life stages in a murine model of allergic airways disease house dust mite (HDM) induced on inflammation and lung function. Methods: Female BALB / c mice were placed in a diet replete or deficient in vitamin D at three-week old. At 8 weeks, females were mated with males on a diet replete in vitamin D. At birth, pups were cross-fostered to assess the effects of vitamin D deficiency at different stages of life, in utero (Vit D -/+), postnatal (Vit D +/-) and whole-life (Vit D - / -) compared to the control group whole-life vitamin D replete (Vit D + / +). At 8 weeks of age, mice of both sexes were challenged for 10 consecutive days intranasally with either HDM extract or saline solution after mild anesthesia. The animals were anesthetized for lung function test and then submitted to euthanasia for bronchoalveolar lavage (BAL) and lung tissue removal 24 hours after the last intranasal challenge. The total BAL cell count and collagen quantification of lung tissue homogenized were evaluated. Results: Vitamin D deficiency did not affect HDM-induced inflammation, which was characterized by BAL eosinophilia. Vitamin D deficiency at any life stage (in utero, postnatal and all life) caused impairment of lung function, increased tissue damping and tissue elastance, being particularly observed in females. On the other hand, the asthma HDM-induced decreased airway distensibility, but only in females and vitamin D do not altered this response. Conclusion: Our results suggest that vitamin D and HDM have different mechanisms that influence in the development of allergic lung disease and furthermore the effects appear to be sex-specific.Introdução: A asma é uma doença crônica das vias aéreas, caracterizada por inflamação e hiperresponsividade brônquica, que atinge aproximadamente 300 milhões de pessoas ao redor do mundo. O aumento da prevalência da asma nos últimos anos tem sido associado ao aumento da deficiência de vitamina D. Cerca de 1 bilhão de pessoas no mundo apresenta níveis insuficientes de vitamina D em função de diversos fatores, tais como a redução de atividades ao ar livre, uso de protetor solar e dieta pobre em vitamina D. Além disso, estudos sugerem que a deficiência de vitamina D possui um efeito direto na função pulmonar, causando alterações na estrutura das vias aéreas e no processo inflamatório. Objetivo: Avaliar o efeito da deficiência de vitamina D em diferentes estágios da vida de camundongos com asma induzida por ácaro domiciliar (house dust mite; HDM) sobre a inflamação e função pulmonar. Métodos: Camundongos BALB/c fêmeas receberam dieta rica ou deficiente em vitamina D a partir da terceira semana de vida. Com 8 semanas de vida, as fêmeas foram acasaladas com machos em dieta rica em vitamina D. Ao nascimento foi realizado o cross-fostering (adoção cruzada) com a prole para que fosse possível avaliar o efeito da deficiência de vitamina D em diferentes estágios da vida, in utero (Vit D -/+), pós-natal (Vit D +/-) e durante toda a vida (Vit D -/-), em comparação ao grupo controle, que recebeu dieta rica em vitamina D durante toda a vida (Vit D +/+). Com 8 semanas de vida, camundongos de ambos os sexos foram desafiados por 10 dias consecutivos por via intranasal, com extrato de HDM ou apenas solução salina. Os animais foram anestesiados para a realização do teste de função pulmonar e então submetidos a eutanásia para a realização do lavado broncoalveolar (LBA) e retirada do tecido pulmonar, 24 horas após o último desafio intranasal. Foi avaliada a contagem total de células do LBA e quantificação de colágeno no homogeneizado de tecido pulmonar. Resultados: A deficiência de vitamina D não afetou a inflamação induzida por HDM, que foi caracterizada por eosinofilia no LBA. A deficiência de vitamina D em qualquer fase da vida dos camundongos (in utero, pós-natal e durante toda a vida) causou uma piora na função pulmonar, aumentando o tissue damping e tissue elastance, sendo observado particularmente em fêmeas. Por outro lado, a asma induzida por HDM diminuiu a distensibilidade das vias aéreas apenas em fêmeas e a vitamina D não alterou essa resposta. Conclusão: Nossos resultados sugerem que a vitamina D e HDM possuem diferentes mecanismos que influenciam no desenvolvimento da doença pulmonar alérgica e, além disso, os efeitos parecem ser dependentes do sexo.Submitted by PPG Pediatria e Saúde da Criança (pediatria-pg@pucrs.br) on 2018-02-16T19:15:31Z No. of bitstreams: 1 Tese final 2018 - artigo publicado.pdf: 1647298 bytes, checksum: 03a39af4be2d469330c9618fb70f9cdd (MD5)Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2018-02-23T16:28:05Z (GMT) No. of bitstreams: 1 Tese final 2018 - artigo publicado.pdf: 1647298 bytes, checksum: 03a39af4be2d469330c9618fb70f9cdd (MD5)Made available in DSpace on 2018-02-23T16:35:09Z (GMT). No. of bitstreams: 1 Tese final 2018 - artigo publicado.pdf: 1647298 bytes, checksum: 03a39af4be2d469330c9618fb70f9cdd (MD5) Previous issue date: 2017-07-12Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESapplication/pdfhttp://tede2.pucrs.br:80/tede2/retrieve/170956/TES_NAILE_KARINE_NUNEZ_CONFIDENCIAL.pdf.jpghttp://tede2.pucrs.br:80/tede2/retrieve/176202/TES_NAILE_KARINE_NUNEZ_COMPLETO.pdf.jpgporPontifícia Universidade Católica do Rio Grande do SulPrograma de Pós-Graduação em Medicina/Pediatria e Saúde da CriançaPUCRSBrasilEscola de MedicinaDeficência de Vitamina DÁcaro da Poeira DomésticaFunção PulmonarModelo MurinoVitamin D DeficiencyHouse Dust MiteLung FunctionMouse ModelCIENCIAS DA SAUDE::MEDICINAEfeitos da deficiência de vitamina D na função pulmonar de um modelo de asma alérgica experimentalinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisTrabalho será publicado como artigo ou livro18 meses23/08/20193098206005268432148500500500600-224747486637135387-9693694523087866272075167498588264571info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da PUC_RSinstname:Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)instacron:PUC_RSORIGINALTES_NAILE_KARINE_NUNEZ_COMPLETO.pdfTES_NAILE_KARINE_NUNEZ_COMPLETO.pdfapplication/pdf1647298http://tede2.pucrs.br/tede2/bitstream/tede/7857/5/TES_NAILE_KARINE_NUNEZ_COMPLETO.pdf03a39af4be2d469330c9618fb70f9cddMD55THUMBNAILTES_NAILE_KARINE_NUNEZ_CONFIDENCIAL.pdf.jpgTES_NAILE_KARINE_NUNEZ_CONFIDENCIAL.pdf.jpgimage/jpeg4094http://tede2.pucrs.br/tede2/bitstream/tede/7857/4/TES_NAILE_KARINE_NUNEZ_CONFIDENCIAL.pdf.jpgb51de7ea43e9031b6bafdc537c15e185MD54TES_NAILE_KARINE_NUNEZ_COMPLETO.pdf.jpgTES_NAILE_KARINE_NUNEZ_COMPLETO.pdf.jpgimage/jpeg5017http://tede2.pucrs.br/tede2/bitstream/tede/7857/7/TES_NAILE_KARINE_NUNEZ_COMPLETO.pdf.jpg022d45de6dbe84dbe80d225571a5a732MD57TEXTTES_NAILE_KARINE_NUNEZ_CONFIDENCIAL.pdf.txtTES_NAILE_KARINE_NUNEZ_CONFIDENCIAL.pdf.txttext/plain1733http://tede2.pucrs.br/tede2/bitstream/tede/7857/3/TES_NAILE_KARINE_NUNEZ_CONFIDENCIAL.pdf.txtcc0a986e8bc3e4b453b25f21bbcebb1eMD53TES_NAILE_KARINE_NUNEZ_COMPLETO.pdf.txtTES_NAILE_KARINE_NUNEZ_COMPLETO.pdf.txttext/plain89449http://tede2.pucrs.br/tede2/bitstream/tede/7857/6/TES_NAILE_KARINE_NUNEZ_COMPLETO.pdf.txtdc41c61fa0e63927d8dc7995c6a3f037MD56LICENSElicense.txtlicense.txttext/plain; charset=utf-8610http://tede2.pucrs.br/tede2/bitstream/tede/7857/1/license.txt5a9d6006225b368ef605ba16b4f6d1beMD51tede/78572019-08-26 12:00:26.122oai:tede2.pucrs.br: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Biblioteca Digital de Teses e Dissertaçõeshttp://tede2.pucrs.br/tede2/PRIhttps://tede2.pucrs.br/oai/requestbiblioteca.central@pucrs.br||opendoar:2019-08-26T15:00:26Biblioteca Digital de Teses e Dissertações da PUC_RS - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)false
dc.title.por.fl_str_mv Efeitos da deficiência de vitamina D na função pulmonar de um modelo de asma alérgica experimental
title Efeitos da deficiência de vitamina D na função pulmonar de um modelo de asma alérgica experimental
spellingShingle Efeitos da deficiência de vitamina D na função pulmonar de um modelo de asma alérgica experimental
Nuñez, Nailê Karine
Deficência de Vitamina D
Ácaro da Poeira Doméstica
Função Pulmonar
Modelo Murino
Vitamin D Deficiency
House Dust Mite
Lung Function
Mouse Model
CIENCIAS DA SAUDE::MEDICINA
title_short Efeitos da deficiência de vitamina D na função pulmonar de um modelo de asma alérgica experimental
title_full Efeitos da deficiência de vitamina D na função pulmonar de um modelo de asma alérgica experimental
title_fullStr Efeitos da deficiência de vitamina D na função pulmonar de um modelo de asma alérgica experimental
title_full_unstemmed Efeitos da deficiência de vitamina D na função pulmonar de um modelo de asma alérgica experimental
title_sort Efeitos da deficiência de vitamina D na função pulmonar de um modelo de asma alérgica experimental
author Nuñez, Nailê Karine
author_facet Nuñez, Nailê Karine
author_role author
dc.contributor.advisor1.fl_str_mv Pitrez, Paulo Márcio Condessa
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/6731821353792634
dc.contributor.advisor-co1.fl_str_mv Zosky, Graeme R.
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/4602172317517240
dc.contributor.author.fl_str_mv Nuñez, Nailê Karine
contributor_str_mv Pitrez, Paulo Márcio Condessa
Zosky, Graeme R.
dc.subject.por.fl_str_mv Deficência de Vitamina D
Ácaro da Poeira Doméstica
Função Pulmonar
Modelo Murino
topic Deficência de Vitamina D
Ácaro da Poeira Doméstica
Função Pulmonar
Modelo Murino
Vitamin D Deficiency
House Dust Mite
Lung Function
Mouse Model
CIENCIAS DA SAUDE::MEDICINA
dc.subject.eng.fl_str_mv Vitamin D Deficiency
House Dust Mite
Lung Function
Mouse Model
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE::MEDICINA
description Background: Asthma is a chronic disease of the airways, characterized by bronchial inflammation and hyperresponsiveness, which affects approximately 300 million people around the world. The increase in the prevalence of asthma in recent years has been associated with an increase in vitamin D deficiency. About 1 billion people in the world have insufficient levels of vitamin D due to many factors such as reduced outdoor activities, sunscreens use and a diet low in vitamin D. In addition, many studies suggest that vitamin D deficiency has a direct effect on lung function, leading to changes in the structure of the airways and in the inflammatory process. Objectives: To evaluate the effect of vitamin D deficiency at different life stages in a murine model of allergic airways disease house dust mite (HDM) induced on inflammation and lung function. Methods: Female BALB / c mice were placed in a diet replete or deficient in vitamin D at three-week old. At 8 weeks, females were mated with males on a diet replete in vitamin D. At birth, pups were cross-fostered to assess the effects of vitamin D deficiency at different stages of life, in utero (Vit D -/+), postnatal (Vit D +/-) and whole-life (Vit D - / -) compared to the control group whole-life vitamin D replete (Vit D + / +). At 8 weeks of age, mice of both sexes were challenged for 10 consecutive days intranasally with either HDM extract or saline solution after mild anesthesia. The animals were anesthetized for lung function test and then submitted to euthanasia for bronchoalveolar lavage (BAL) and lung tissue removal 24 hours after the last intranasal challenge. The total BAL cell count and collagen quantification of lung tissue homogenized were evaluated. Results: Vitamin D deficiency did not affect HDM-induced inflammation, which was characterized by BAL eosinophilia. Vitamin D deficiency at any life stage (in utero, postnatal and all life) caused impairment of lung function, increased tissue damping and tissue elastance, being particularly observed in females. On the other hand, the asthma HDM-induced decreased airway distensibility, but only in females and vitamin D do not altered this response. Conclusion: Our results suggest that vitamin D and HDM have different mechanisms that influence in the development of allergic lung disease and furthermore the effects appear to be sex-specific.
publishDate 2017
dc.date.issued.fl_str_mv 2017-07-12
dc.date.accessioned.fl_str_mv 2018-02-23T16:35:09Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://tede2.pucrs.br/tede2/handle/tede/7857
url http://tede2.pucrs.br/tede2/handle/tede/7857
dc.language.iso.fl_str_mv por
language por
dc.relation.program.fl_str_mv 3098206005268432148
dc.relation.confidence.fl_str_mv 500
500
500
600
dc.relation.department.fl_str_mv -224747486637135387
dc.relation.cnpq.fl_str_mv -969369452308786627
dc.relation.sponsorship.fl_str_mv 2075167498588264571
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Pontifícia Universidade Católica do Rio Grande do Sul
dc.publisher.program.fl_str_mv Programa de Pós-Graduação em Medicina/Pediatria e Saúde da Criança
dc.publisher.initials.fl_str_mv PUCRS
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Escola de Medicina
publisher.none.fl_str_mv Pontifícia Universidade Católica do Rio Grande do Sul
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações da PUC_RS
instname:Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)
instacron:PUC_RS
instname_str Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)
instacron_str PUC_RS
institution PUC_RS
reponame_str Biblioteca Digital de Teses e Dissertações da PUC_RS
collection Biblioteca Digital de Teses e Dissertações da PUC_RS
bitstream.url.fl_str_mv http://tede2.pucrs.br/tede2/bitstream/tede/7857/5/TES_NAILE_KARINE_NUNEZ_COMPLETO.pdf
http://tede2.pucrs.br/tede2/bitstream/tede/7857/4/TES_NAILE_KARINE_NUNEZ_CONFIDENCIAL.pdf.jpg
http://tede2.pucrs.br/tede2/bitstream/tede/7857/7/TES_NAILE_KARINE_NUNEZ_COMPLETO.pdf.jpg
http://tede2.pucrs.br/tede2/bitstream/tede/7857/3/TES_NAILE_KARINE_NUNEZ_CONFIDENCIAL.pdf.txt
http://tede2.pucrs.br/tede2/bitstream/tede/7857/6/TES_NAILE_KARINE_NUNEZ_COMPLETO.pdf.txt
http://tede2.pucrs.br/tede2/bitstream/tede/7857/1/license.txt
bitstream.checksum.fl_str_mv 03a39af4be2d469330c9618fb70f9cdd
b51de7ea43e9031b6bafdc537c15e185
022d45de6dbe84dbe80d225571a5a732
cc0a986e8bc3e4b453b25f21bbcebb1e
dc41c61fa0e63927d8dc7995c6a3f037
5a9d6006225b368ef605ba16b4f6d1be
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
MD5
MD5
repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações da PUC_RS - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)
repository.mail.fl_str_mv biblioteca.central@pucrs.br||
_version_ 1799765330712592384