Sono e vitamina D: ensaios clínico e pré-clínico
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Data
2018-02-22
Autores
Oliveira, Daniela Leite de [UNIFESP]
Orientadores
Andersen, Monica Levy [UNIFESP]
Tipo
Dissertação de mestrado
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Introdução: A vitamina D é um hormônio importante para o metabolismo ósseo. As principais moléculas envolvidas em seu metabolismo são as enzimas CYP2R1 e CYP27B1 e, o VDR. Recentemente, tem sido proposto uma associação entre sono e vitamina D. Objetivos: Avaliar o efeito da duração de sono e da apneia obstrutiva do sono sobre os níveis séricos de vitamina D em uma amostra populacional. Avaliar o efeito da privação de sono na via regulatória da vitamina D em modelo animal. Métodos: O estudo clínico fez parte da coorte EPISONO, que incluiu 712 voluntários submetidos a polissonografia, preenchimento de questionários e dosagem sérica de 25(OH)D. Para o estudo em modelo animal, foram utilizados 70 ratos machos Wistar adultos distribuídos em 7 grupos: controle, privação de sono paradoxal (PSP) por 24, 48, 72 e 96 h, privação de sono total (PST) por 6 horas e, restrição de sono (RS) por 21 dias. Após a eutanásia, o sangue foi coletado para a avaliação bioquímica e, os tecidos fígado, rim, hipotálamo, córtex pré-frontal e hipocampo foram utilizados para avaliação dos genes VDR, CYP27B1 e CYP2R1. Resultados: No estudo clínico, a duração de sono menor que 6 h foi associada com níveis séricos de 25(OH)D<20 ng/mL, principalmente nos homens. No estudo pré-clínico, os protocolos de privação de sono não alteraram os níveis séricos de vitamina D, 25(OH)D (forma inativa) ou 1,25(OH)2D (forma ativa), em relação ao grupo controle. O gene CYP2R1 aumentou sua expressão no fígado (PSP24, PSP48 e RS) e no hipotálamo (PSP72). A expressão gênica de CYP27B1 foi maior no hipotálamo (PSP48) e no córtex pré-frontal (PST6, PSP48, PSP72 e PSP96). Conclusões: Nossos achados indicam que o sono possua um papel na via regulatória da vitamina D.
Introduction: Vitamin D is an important hormone for bone metabolism. The main molecules involved in its metabolism are the enzymes CYP2R1 and CYP27B1 and, the VDR. Recently, an association between sleep and vitamin D has been proposed. Objectives: To evaluate the effect of sleep duration and obstructive sleep apnea on serum vitamin D levels in a population sample. To evaluate the effect of sleep deprivation on the regulatory pathway of vitamin D in an animal model. Methods: The clinical study was part of the prospective EPISONO cohort, which included 712 volunteers who underwent polysomnography, answered questionnaires and collected serum for 25(OH)D quantification. In the animal study, 70 adult male Wistar rats were distributed in 7 groups: control, paradoxical sleep deprivation (PSD) for 24, 48, 72 and 96 h, total sleep deprivation (TSD) for 6 h and, sleep restriction (SR) for 21 days. After the euthanasia, the blood was collected for the biochemical evaluation and, the liver, kidney, hypothalamus, pre-frontal cortex and hippocampus tissues were collected for evaluation of the VDR, CYP27B1 and CYP2R1 genes expression. Results: In the clinical study, sleep duration lower than 6 h was associated with serum levels of 25(OH)D<20 ng/mL, especially in men. In the pre-clinical study, sleep deprivation protocols did not change serum levels of vitamin D, 25(OH)D (inactive form) or 1,25(OH)2D (active form), in relation to control group. The CYP2R1 gene increased its expression in the liver (PSD24, PSD48 and SR) and in the hypothalamus (PSD72). Gene expression of CYP27B1 was higher in the hypothalamus (PSD48) and in the pre-frontal cortex (TSD6, PSD48, PSD72 and PSD96). Conclusions: Our findings indicate that sleep plays a role in the regulatory pathway of vitamin D.
Introduction: Vitamin D is an important hormone for bone metabolism. The main molecules involved in its metabolism are the enzymes CYP2R1 and CYP27B1 and, the VDR. Recently, an association between sleep and vitamin D has been proposed. Objectives: To evaluate the effect of sleep duration and obstructive sleep apnea on serum vitamin D levels in a population sample. To evaluate the effect of sleep deprivation on the regulatory pathway of vitamin D in an animal model. Methods: The clinical study was part of the prospective EPISONO cohort, which included 712 volunteers who underwent polysomnography, answered questionnaires and collected serum for 25(OH)D quantification. In the animal study, 70 adult male Wistar rats were distributed in 7 groups: control, paradoxical sleep deprivation (PSD) for 24, 48, 72 and 96 h, total sleep deprivation (TSD) for 6 h and, sleep restriction (SR) for 21 days. After the euthanasia, the blood was collected for the biochemical evaluation and, the liver, kidney, hypothalamus, pre-frontal cortex and hippocampus tissues were collected for evaluation of the VDR, CYP27B1 and CYP2R1 genes expression. Results: In the clinical study, sleep duration lower than 6 h was associated with serum levels of 25(OH)D<20 ng/mL, especially in men. In the pre-clinical study, sleep deprivation protocols did not change serum levels of vitamin D, 25(OH)D (inactive form) or 1,25(OH)2D (active form), in relation to control group. The CYP2R1 gene increased its expression in the liver (PSD24, PSD48 and SR) and in the hypothalamus (PSD72). Gene expression of CYP27B1 was higher in the hypothalamus (PSD48) and in the pre-frontal cortex (TSD6, PSD48, PSD72 and PSD96). Conclusions: Our findings indicate that sleep plays a role in the regulatory pathway of vitamin D.
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OLIVEIRA, Daniela Leite de. Sono e vitamina D: ensaios clínico e pré-clínico. 2018. 109 f. Dissertação (Mestrado em Psicobiologia) - Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2018.