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Previous issue date: 2015-07-17 / Conselho Nacional de Pesquisa e Desenvolvimento Cient?fico e Tecnol?gico - CNPq / Introduction: Adversities faced during the prenatal period can be related to the onset of
diseases in adulthood. However, little is known about its effects on the respiratory system.
Aims: To assess the effects of restraint prenatal stress, in two different moments of
pregnancy, on pulmonary function and inflammatory profile in male and female mice exposed
to a ovalbumin (OVA) induced asthma model.
Methods: Male and female BALB/c mice were divided into 3 groups: control (CON),
prenatal stress from the second week of pregnancy (PNS1) and prenatal stress on the last
week of pregnancy (PNS2). Pups were weighted on 3 different moments (days 1, 10 and 21).
As adults, the fear/anxiety behavior was evaluated in the open field (between days 50? and
54?). The ovalbumin-induced asthma model was performed at day 56, followed by the
analysis of lung function (airway resistance, tissue damping and elastance), collection of
bronchoalveolar lavage fluid, total and differential cell count and inflammatory cytokines
evaluation. The left lung was removed and processed for histological analysis.
Results: There was a significant decrease (p<0.05) in the number of entries and time spent in
the central quadrant only in PNS1 group compared to controls. Females (PNS1) also
presented an improvement in the lung function, measured as airway resistance, tissue
damping and pulmonary elastance (p<0.05). When female differential cell count was
analyzed, PNS1 group showed a significant increase in the percentage of neutrophils
(p<0.01), lymphocytes (p<0.05) and a significant decrease of eosinophils (p<0.05) when
compared to the control group. There was also a decrease in the BAL inflammatory cytokines,
including a significant reduction in IL-5 and IL-13 in males of PNS1 (p<0.001 and p<0.01)
and PNS2 (p<0.01 and p<0.01) when compared to controls. In females, a significant reduction in the secretion of IL-4, IL-5 and IL-13 in both PNS1 (p<0.05, p<0.001 and p<0.01) and
PNS2 (p<0.01, p<0.001 and p<0.05) were demonstrated.
Conclusion: The results of this study indicate that prenatal stress, from the second week of
pregnancy (PNS1), reduces the impact of asthma development in adult female mice, showing
an improved pulmonary function and a lower allergic inflammatory response in the lungs. / Introdu??o: Adversidades enfrentadas no per?odo pr?-natal podem estar implicadas na
programa??o fetal e no surgimento de doen?as na vida adulta. No entanto, pouco se sabe
sobre os efeitos do estresse neste per?odo sobre o sistema respirat?rio.
Objetivos: Avaliar os efeitos do estresse pr?-natal por conten??o, em dois diferentes
momentos da prenhez, sobre a fun??o pulmonar e o perfil inflamat?rio em camundongos
machos e f?meas, expostos a um modelo de asma induzida por ovalbumina (OVA).
Materiais e m?todos: Foram utilizados camundongos BALB/c machos e f?meas divididos
em tr?s diferentes grupos controle (CON), estresse pr?-natal a partir da 2? semana (PNS1) e
estresse pr?-natal na ?ltima semana (PNS2). A pesagem da prole foi feita em 3 diferentes
momentos (dias 1, 10 e 21). Quando adultos, foi avaliado o comportamento de
medo/ansiedade no campo aberto (entre o 50? e 54? dia). No 56? dia foi realizada a aplica??o
do modelo de asma por ovalbumina com posterior an?lise do teste de fun??o pulmonar
(resist?ncia das vias a?reas, amortecimento do tecido e elast?ncia), al?m da coleta de lavado
broncoalveolar para contagem total e diferencial de c?lulas e avalia??o de citocinas
inflamat?rias. O pulm?o esquerdo foi retirado e processado para an?lise histol?gica.
Resultados: Houve diminui??o significativa (p<0,05) do n?mero de entradas e tempo
despendido no quadrante central somente no grupo PNS1 quando comparado aos controles.
Melhora na fun??o pulmonar das f?meas nos par?metros de resist?ncia das vias a?reas,
amortecimento do tecido e elast?ncia pulmonar (p<0,05). Na contagem diferencial de c?lulas
das f?meas, o grupo PNS1 apresentou um aumento percentual significativo dos neutr?filos
(p<0,01) e linf?citos (p<0,05) e uma diminui??o significativa de eosin?filos (p<0,05), quando
comparados ao grupo controle. Tamb?m houve diminui??o das citocinas inflamat?rias com
redu??o significativa na secre??o de IL-5 e IL-13 no LBA dos machos do grupo PNS1 (p<0,001 e p<0,01) e PNS2 (p<0,01 e p<0,01), quando comparados com o grupo controle.
Nas f?meas houve uma redu??o significativa na secre??o de IL-4, IL-5 e IL-13 nos grupos
PNS1 (p<0,05, p<0,001 e p<0,01) e PNS2 (p<0,01, p<0,001 e p<0,05)
Conclus?o: Os resultados deste estudo indicam que o estresse pr?-natal, a partir da segunda
semana de prenhez (PNS1), reduziu o impacto do desenvolvimento da asma em camundongos
f?meas na idade adulta, mostrando uma melhor fun??o pulmonar e menor resposta
inflamat?ria al?rgica no pulm?o.
| Identifer | oai:union.ndltd.org:IBICT/oai:tede2.pucrs.br:tede/6251 |
| Date | 17 July 2015 |
| Creators | Vargas, Mauro Henrique Moraes |
| Contributors | Donadio, M?rcio Vin?cius Fagundes, Pitrez, Paulo M?rcio Condessa |
| Publisher | Pontif?cia Universidade Cat?lica do Rio Grande do Sul, Programa de P?s-Gradua??o em Medicina/Pediatria e Sa?de da Crian?a, PUCRS, Brasil, Faculdade de Medicina |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da PUC_RS, instname:Pontifícia Universidade Católica do Rio Grande do Sul, instacron:PUC_RS |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 3098206005268432148, 600, 600, 600, 600, -8624664729441623247, -969369452308786627, -2555911436985713659 |
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