Efeitos da deficiência de vitamina D na função pulmonar de um modelo de asma alérgica experimental
Autor(a) principal: | |
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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. |
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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 |
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2018-02-23T16:35:09Z |
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doctoralThesis |
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http://tede2.pucrs.br/tede2/handle/tede/7857 |
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Pontifícia Universidade Católica do Rio Grande do Sul |
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