Estresse, envelhecimento e osteoporose: estudo experimental da perda óssea, da expressão de citocinas pró-inflamatórias e dos marcadores ósseos RANKL, RANK e OPG, em ratos

• Autor(a) principal: Valente, Fabrício Luciani
• Data de Publicação: 2011
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: LOCUS Repositório Institucional da UFV
• Texto Completo: http://locus.ufv.br/handle/123456789/1447
• topic: Perda óssea; Modelo experimental; Ratos; Bone loss; Experimental model; Rats; CNPQ::CIENCIAS AGRARIAS::MEDICINA VETERINARIA::PATOLOGIA ANIMAL

Aging, stress and osteoporosis are conditions that have taken great importance in modern world not only as reflection of lifestyle, but also due to the increasing life expectancy of populations. These conditions share many common mechanisms and modulating one of them may affect the others by direct and indirect means. Osteoporosis is a common disease among the elderly and, although its cause may be multifactorial, many processes associated with aging contribute to its pathogenesis. Chronic stress can impair bone mass and it can be considered an important factor that affects life quality for seniors, as does osteoporosis. This study aims to evaluate the effect of a chronic mild stress protocol on bone parameters in rats, and the role of sex and age on this process. To do that, male and female rats, 5 and 22-24 months old, were submitted to mild stressors during 28 days. We included cold, heat, immobilization, tilt cage, isolation, overnight illumination, and water and food deprivation; each stressor was applied four times during the period. Animals of both sexes, young and aged, were kept with water and feed at will, with no interventions, to serve as control. Rats were weighed at the beginning and at the end of the period. After euthanasia, rats had their bones and blood collected. Femur, tibia and lumbar vertebra were analyzed by densitometry. Biomechanical tests evaluated maximal strength, toughness and stiffness of the head and shaft of femoral head and diaphysis by bending test. Histomorphometric analysis provided trabecular bone volume from femoral head and vertebral body, and measures of cortical bone and marrow cavity from femoral diaphysis cross-section. Immunohistochemistry was performed to analyze expression of RANKL, RANK and OPG in femur and vertebra. From blood, ELISA detected testosterone, estradiol, IL-1β, IL-6 and TNF-α. Stress was able to decrease body weight, regardless of sex and age. The protocol employed also showed ability to reduce many of the parameters assessed, and that could harm bone health. However, stress affected a greater number of variables among young than aged animals. This result should be interpreted with caution.Probably aging could slow down bone response to the stimuli caused by stress. But with chronic stimuli, the effects of stress on bone metabolism could be more severe in the elderly. About sex hormones, although not statistically significant, a decrease in testosterone concentration in the groups subjected to stress could be perceived. Considering estradiol, there was an opposite behavior between the group of male and female group in the former, stress increased hormone concentration, while in the latter hormone levels were decreased. Individual variations were wide, so a better delineation of the model makes necessary, possibly involving a larger number of samples. Stress also showed only an indirect effect on IL-1β levels, which decreased in young animals but increased in the senile. TNF-α decreased in males and it increased in females after stress. Differences in RANKL expression assessed by immunohistochemistry were perceived only related to stress. Probably because of the inducible nature of those substances, their investigation may become more heterogeneous. Since the proposed model is a novel model, some methodological adjustments are made necessary. All these data are presented in chapters where summaries in Portuguese and English and a set of keywords can be found.