Efeitos do transplante de células mononucleares de medula óssea na hipertensão espontânea em ratos

Detalhes bibliográficos
Autor(a) principal: ALMEIDA, Thalles Ramos
Data de Publicação: 2012
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFTM
Texto Completo: http://bdtd.uftm.edu.br/handle/tede/181
Resumo: No presente estudo, os efeitos do transplante de células mononucleares (TMN) extraídas de medula óssea de ratos espontaneamente hipertensos (SHR) adultos (Ad) ou jovens (Jv) isogênicos ou de ratos Wistar-Kyoto (WKY) normotensos alogênicos sobre os níveis de pressão arterial sistêmica de SHRs fêmeas foram avaliados. Células mononucleares de medula óssea foram retiradas de tíbias, fêmurs e úmeros de SHRs doadores machos isogênicos adultos (de 16 semanas de idade, TMN-Ad, n=4) ou jovens (de 4 semanas de idade, TMN-Jv, n=2) ou de ratos WKY normotensos (de 16 semanas de idade, TMN-WKY, n=2) e injetadas (5x106 cels./rato, i.v.) em SHRs receptoras fêmeas de 16-20 semanas de idade (grupos TMN-Ad, n=10, TMN-Jv, n=7 e TMN-WKY, n=7). As células mononucleares foram marcadas com o corante fluorescente celltracker CM-DiI, previamente à administração. Ratas SHRs fêmeas, recebendo apenas o veículo, formaram o grupo controle (CON, n=15). Pressão arterial (PA) indireta foi registrada diariamente ou a cada dois dias por meio do método de oclusão da artéria caudal por uma semana antes até duas semanas, após o transplante em todos os grupos experimentais. No final desse período, após prévia canulação (24-48 horas antes), todos os animais foram submetidos ao registro direto da pressão arterial pulsátil por 01 hora, em condições estáveis e de repouso. Em seguida, posteriormente à anestesia com pentobarbital sódico, os animais foram eutanasiados. Concluído o sacrifício, microscopia de fluorescência foi realizada em cortes histológicos teciduais dos órgãos removidos, incluindo rins, baço, pulmões e coração, a fim de se verificar a presença de células de SHR doadores (celltracker CM-DiI+). Em ambos os grupos submetidos ao transplante isogênico (TMN-Ad e TMN-Jv), a PA foi reduzida após o terceiro dia, permanecendo baixa até o final do período de observação. Confirmando estes achados, os valores de PA média avaliados por meio de medida direta foram de 137±4mmHg no grupo TMN-Ad e 136±3mmHg no grupo TMN-Jv (versus 163±5mmHg no grupo CON, p<0.005). Em adição, nenhuma diferença nos parâmetros de variabilidade da frequência cardíaca e na sensibilidade barorreflexa espontânea foram observadas entre os grupos, enquanto que a variância, o componente VLF (very low frequency) e o componente LF (low frequency) da variabilidade da pressão arterial foram significativamente reduzidos, em ambos os grupos TMN-Ad e TMN-Jv. Também se observou uma diminuição na hipertrofia cardíaca, provavelmente pela redução da sobrecarga hemodinâmica imposta ao ventrículo esquerdo. Não foram observadas modificações na densidade glomerular nos grupos TMN-Jv e TMN-Ad, comparados ao grupo CON. Pequenas quantidades de células foram encontradas em vários tecidos, incluindo os rins, enquanto um grande número de células estava marcadamente presente no baço dos animais que receberam transplante isogênico. Por outro lado, nas SHRs submetidas ao transplante alogênico com células de ratos WKY (grupo TMN-WKY), ao final do período de observação, nenhuma queda da PA foi observada. Em concordância, a PA média direta medida nos animais TMN-WKY não diferiu dos respectivos animais controles. Nenhuma modificação foi observada na variabilidade cardiovascular, sensibilidade barorreflexa, hipertrofia cardíaca e densidade glomerular dos animais TMN-WKY. No transplante alogênico, células WKY transplantadas foram encontradas apenas no baço, sugerindo rejeição das células. Esses achados sugerem que o transplante de células mononucleares de medula óssea isogênica, em animais imunocompetentes, de diferentes idades é capaz de reduzir a pressão arterial associada à hipertensão arterial sistêmica.
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spelling Efeitos do transplante de células mononucleares de medula óssea na hipertensão espontânea em ratosMedula ósseaTransplante de medula ósseaCélulas da medula ósseaHipertensãoBone marrowBone marrow transplantationBone marrow cellsHypertensionBiologia GeralNo presente estudo, os efeitos do transplante de células mononucleares (TMN) extraídas de medula óssea de ratos espontaneamente hipertensos (SHR) adultos (Ad) ou jovens (Jv) isogênicos ou de ratos Wistar-Kyoto (WKY) normotensos alogênicos sobre os níveis de pressão arterial sistêmica de SHRs fêmeas foram avaliados. Células mononucleares de medula óssea foram retiradas de tíbias, fêmurs e úmeros de SHRs doadores machos isogênicos adultos (de 16 semanas de idade, TMN-Ad, n=4) ou jovens (de 4 semanas de idade, TMN-Jv, n=2) ou de ratos WKY normotensos (de 16 semanas de idade, TMN-WKY, n=2) e injetadas (5x106 cels./rato, i.v.) em SHRs receptoras fêmeas de 16-20 semanas de idade (grupos TMN-Ad, n=10, TMN-Jv, n=7 e TMN-WKY, n=7). As células mononucleares foram marcadas com o corante fluorescente celltracker CM-DiI, previamente à administração. Ratas SHRs fêmeas, recebendo apenas o veículo, formaram o grupo controle (CON, n=15). Pressão arterial (PA) indireta foi registrada diariamente ou a cada dois dias por meio do método de oclusão da artéria caudal por uma semana antes até duas semanas, após o transplante em todos os grupos experimentais. No final desse período, após prévia canulação (24-48 horas antes), todos os animais foram submetidos ao registro direto da pressão arterial pulsátil por 01 hora, em condições estáveis e de repouso. Em seguida, posteriormente à anestesia com pentobarbital sódico, os animais foram eutanasiados. Concluído o sacrifício, microscopia de fluorescência foi realizada em cortes histológicos teciduais dos órgãos removidos, incluindo rins, baço, pulmões e coração, a fim de se verificar a presença de células de SHR doadores (celltracker CM-DiI+). Em ambos os grupos submetidos ao transplante isogênico (TMN-Ad e TMN-Jv), a PA foi reduzida após o terceiro dia, permanecendo baixa até o final do período de observação. Confirmando estes achados, os valores de PA média avaliados por meio de medida direta foram de 137±4mmHg no grupo TMN-Ad e 136±3mmHg no grupo TMN-Jv (versus 163±5mmHg no grupo CON, p<0.005). Em adição, nenhuma diferença nos parâmetros de variabilidade da frequência cardíaca e na sensibilidade barorreflexa espontânea foram observadas entre os grupos, enquanto que a variância, o componente VLF (very low frequency) e o componente LF (low frequency) da variabilidade da pressão arterial foram significativamente reduzidos, em ambos os grupos TMN-Ad e TMN-Jv. Também se observou uma diminuição na hipertrofia cardíaca, provavelmente pela redução da sobrecarga hemodinâmica imposta ao ventrículo esquerdo. Não foram observadas modificações na densidade glomerular nos grupos TMN-Jv e TMN-Ad, comparados ao grupo CON. Pequenas quantidades de células foram encontradas em vários tecidos, incluindo os rins, enquanto um grande número de células estava marcadamente presente no baço dos animais que receberam transplante isogênico. Por outro lado, nas SHRs submetidas ao transplante alogênico com células de ratos WKY (grupo TMN-WKY), ao final do período de observação, nenhuma queda da PA foi observada. Em concordância, a PA média direta medida nos animais TMN-WKY não diferiu dos respectivos animais controles. Nenhuma modificação foi observada na variabilidade cardiovascular, sensibilidade barorreflexa, hipertrofia cardíaca e densidade glomerular dos animais TMN-WKY. No transplante alogênico, células WKY transplantadas foram encontradas apenas no baço, sugerindo rejeição das células. Esses achados sugerem que o transplante de células mononucleares de medula óssea isogênica, em animais imunocompetentes, de diferentes idades é capaz de reduzir a pressão arterial associada à hipertensão arterial sistêmica.In the present study, the effects of transplantation of bone marrow-mononuclear cells (MNT) from isogenic adult (Ad) or young (Yo) spontaneously hypertensive rats (SHR) or allogenic normotensive Wistar-Kyoto (WKY) rats on systemic arterial blood pressure levels of receptor SHRs were assessed. Bone marrow-mononuclear cells were extracted from tibiae, femurs and umerus of isogenic male adult (16 weeks-old aged rats, MNT-Ad, n=4) or young (4 weeks-old rats, MNT-Yo, n=2) donor SHRs or allogenic male adult normotensive WKY rats (16 weeks-old aged rats, MNT-WKY, n=2) and injected (5x106 cells/rats, i.v.) in 24 female 16-20 weeks-old aged receptor SHRs (respectively, MNT-Ad, n=10, MNT-Yo, n=7 and MNT-WKY, n=7). Mononuclear cells were labeled using fluorescent stain celltracker CM-DiI, before administration in order to track cell destination. Age-matched female SHRs receiving only vehicle formed control groups (CON, n=15). Indirect arterial pressure (AP) were daily or each two days recorded by means of caudal artery occlusion method during one week before and until two weeks after cell transplantation in all experimental groups. At the ending, after previous canulation (performed 24-48 hours before), all animals were submitted to a pulsatile direct AP recording session during one hour in conscious freely moving conditions. Following, all animals were euthanized under supra-dosage of anesthetic sodium thiopental (100mg/Kg, i.p.) and fluorescence microscopy was used on thin sections of several organs including kidneys, spleen, lung and heart in order to track donor CM-DiI+ cells. In both groups submitted to isogenic transplantation (MNT-Ad and MNT-Yo), AP was significantly reduced after the third day, remaining lower until the end of observation period. Confirming these findings, the values of mean AP directly measured were 137±4mmHg in MNT-Ad group and 136±3mmHg in MNT-Yo group (versus 163±5mmHg in CON group, p<0.005). In addition, no difference in heart rate variability and spontaneous baroreflex sensitivity parameters were observed while variance, very low frequency and low frequency components of arterial pressure variability were significantly lowers in both MNT-Ad and MNT-Yo groups. A significant reduction in cardiac hypertrophy, probably due to the relief in hemodynamic overload on left ventricle was also observed. No changes were verified in glomerular density in both MNT-Yo and MNT-Ad groups, compared to CON group. Small amounts of CM-DiI+ cells were found in several tissues, including the kidneys, while a great amount of labeled transplanted cells were present into the spleen of the animals that received isogenic transplantation. On the other hand, in SHRs submitted to allogenic transplantation with WKY cells (MNT-WKY group), no reduction in AP was observed after eleven day of observation. According to this, direct AP measurements in MNT-WKY animals were not different of control animals. In addition, no changes in cardiovascular variability, baroreflex sensitivity, cardiac hypertrophy and glomerular density were observed in MNT-WKY animals. In this allogenic transplantation, labeled transplanted WKY cells were found only into the spleen, suggesting immune rejection. All these findings indicate that isogenic, in immunocompetent animals, transplantation of bone marrow-mononuclear cells with different ages is able to consistently reduce arterial blood pressure in systemic arterial hypertension.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESUniversidade Federal do Triângulo MineiroInstituto de Ciências da Saúde - ICS::Curso de MedicinaBrasilUFTMCurso de Pós-Graduação em Ciências FisiológicasSILVA, Valdo José Dias da640.030.516-53http://lattes.cnpq.br/4763314549493316ALMEIDA, Thalles Ramos2015-12-08T17:16:52Z2012-08-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfapplication/pdfALMEIDA, Thalles Ramos. Efeitos do transplante de células mononucleares de medula óssea na hipertensão espontânea em ratos. 2012. 99F. 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dc.title.none.fl_str_mv Efeitos do transplante de células mononucleares de medula óssea na hipertensão espontânea em ratos
title Efeitos do transplante de células mononucleares de medula óssea na hipertensão espontânea em ratos
spellingShingle Efeitos do transplante de células mononucleares de medula óssea na hipertensão espontânea em ratos
ALMEIDA, Thalles Ramos
Medula óssea
Transplante de medula óssea
Células da medula óssea
Hipertensão
Bone marrow
Bone marrow transplantation
Bone marrow cells
Hypertension
Biologia Geral
title_short Efeitos do transplante de células mononucleares de medula óssea na hipertensão espontânea em ratos
title_full Efeitos do transplante de células mononucleares de medula óssea na hipertensão espontânea em ratos
title_fullStr Efeitos do transplante de células mononucleares de medula óssea na hipertensão espontânea em ratos
title_full_unstemmed Efeitos do transplante de células mononucleares de medula óssea na hipertensão espontânea em ratos
title_sort Efeitos do transplante de células mononucleares de medula óssea na hipertensão espontânea em ratos
author ALMEIDA, Thalles Ramos
author_facet ALMEIDA, Thalles Ramos
author_role author
dc.contributor.none.fl_str_mv SILVA, Valdo José Dias da
640.030.516-53
http://lattes.cnpq.br/4763314549493316
dc.contributor.author.fl_str_mv ALMEIDA, Thalles Ramos
dc.subject.por.fl_str_mv Medula óssea
Transplante de medula óssea
Células da medula óssea
Hipertensão
Bone marrow
Bone marrow transplantation
Bone marrow cells
Hypertension
Biologia Geral
topic Medula óssea
Transplante de medula óssea
Células da medula óssea
Hipertensão
Bone marrow
Bone marrow transplantation
Bone marrow cells
Hypertension
Biologia Geral
description No presente estudo, os efeitos do transplante de células mononucleares (TMN) extraídas de medula óssea de ratos espontaneamente hipertensos (SHR) adultos (Ad) ou jovens (Jv) isogênicos ou de ratos Wistar-Kyoto (WKY) normotensos alogênicos sobre os níveis de pressão arterial sistêmica de SHRs fêmeas foram avaliados. Células mononucleares de medula óssea foram retiradas de tíbias, fêmurs e úmeros de SHRs doadores machos isogênicos adultos (de 16 semanas de idade, TMN-Ad, n=4) ou jovens (de 4 semanas de idade, TMN-Jv, n=2) ou de ratos WKY normotensos (de 16 semanas de idade, TMN-WKY, n=2) e injetadas (5x106 cels./rato, i.v.) em SHRs receptoras fêmeas de 16-20 semanas de idade (grupos TMN-Ad, n=10, TMN-Jv, n=7 e TMN-WKY, n=7). As células mononucleares foram marcadas com o corante fluorescente celltracker CM-DiI, previamente à administração. Ratas SHRs fêmeas, recebendo apenas o veículo, formaram o grupo controle (CON, n=15). Pressão arterial (PA) indireta foi registrada diariamente ou a cada dois dias por meio do método de oclusão da artéria caudal por uma semana antes até duas semanas, após o transplante em todos os grupos experimentais. No final desse período, após prévia canulação (24-48 horas antes), todos os animais foram submetidos ao registro direto da pressão arterial pulsátil por 01 hora, em condições estáveis e de repouso. Em seguida, posteriormente à anestesia com pentobarbital sódico, os animais foram eutanasiados. Concluído o sacrifício, microscopia de fluorescência foi realizada em cortes histológicos teciduais dos órgãos removidos, incluindo rins, baço, pulmões e coração, a fim de se verificar a presença de células de SHR doadores (celltracker CM-DiI+). Em ambos os grupos submetidos ao transplante isogênico (TMN-Ad e TMN-Jv), a PA foi reduzida após o terceiro dia, permanecendo baixa até o final do período de observação. Confirmando estes achados, os valores de PA média avaliados por meio de medida direta foram de 137±4mmHg no grupo TMN-Ad e 136±3mmHg no grupo TMN-Jv (versus 163±5mmHg no grupo CON, p<0.005). Em adição, nenhuma diferença nos parâmetros de variabilidade da frequência cardíaca e na sensibilidade barorreflexa espontânea foram observadas entre os grupos, enquanto que a variância, o componente VLF (very low frequency) e o componente LF (low frequency) da variabilidade da pressão arterial foram significativamente reduzidos, em ambos os grupos TMN-Ad e TMN-Jv. Também se observou uma diminuição na hipertrofia cardíaca, provavelmente pela redução da sobrecarga hemodinâmica imposta ao ventrículo esquerdo. Não foram observadas modificações na densidade glomerular nos grupos TMN-Jv e TMN-Ad, comparados ao grupo CON. Pequenas quantidades de células foram encontradas em vários tecidos, incluindo os rins, enquanto um grande número de células estava marcadamente presente no baço dos animais que receberam transplante isogênico. Por outro lado, nas SHRs submetidas ao transplante alogênico com células de ratos WKY (grupo TMN-WKY), ao final do período de observação, nenhuma queda da PA foi observada. Em concordância, a PA média direta medida nos animais TMN-WKY não diferiu dos respectivos animais controles. Nenhuma modificação foi observada na variabilidade cardiovascular, sensibilidade barorreflexa, hipertrofia cardíaca e densidade glomerular dos animais TMN-WKY. No transplante alogênico, células WKY transplantadas foram encontradas apenas no baço, sugerindo rejeição das células. Esses achados sugerem que o transplante de células mononucleares de medula óssea isogênica, em animais imunocompetentes, de diferentes idades é capaz de reduzir a pressão arterial associada à hipertensão arterial sistêmica.
publishDate 2012
dc.date.none.fl_str_mv 2012-08-01
2015-12-08T17:16:52Z
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 ALMEIDA, Thalles Ramos. Efeitos do transplante de células mononucleares de medula óssea na hipertensão espontânea em ratos. 2012. 99F. Dissertação (Mestrado em Ciências Fisiológicas) - Curso de Pós-Graduação em Ciências Fisiológicas - Bioquímica, Fisiologia e Farmacologia, Universidade Federal do Triângulo Mineiro, Uberaba, 2012.
http://bdtd.uftm.edu.br/handle/tede/181
identifier_str_mv ALMEIDA, Thalles Ramos. Efeitos do transplante de células mononucleares de medula óssea na hipertensão espontânea em ratos. 2012. 99F. Dissertação (Mestrado em Ciências Fisiológicas) - Curso de Pós-Graduação em Ciências Fisiológicas - Bioquímica, Fisiologia e Farmacologia, Universidade Federal do Triângulo Mineiro, Uberaba, 2012.
url http://bdtd.uftm.edu.br/handle/tede/181
dc.language.iso.fl_str_mv por
language por
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dc.publisher.none.fl_str_mv Universidade Federal do Triângulo Mineiro
Instituto de Ciências da Saúde - ICS::Curso de Medicina
Brasil
UFTM
Curso de Pós-Graduação em Ciências Fisiológicas
publisher.none.fl_str_mv Universidade Federal do Triângulo Mineiro
Instituto de Ciências da Saúde - ICS::Curso de Medicina
Brasil
UFTM
Curso de Pós-Graduação em Ciências Fisiológicas
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