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Étude de l'impact du sexe sur la coagulation vitamine K dépendante chez le rat

Abstract : Vitamin K antagonists (VKA) are inhibitors of the recycling mechanism of vitamin K. Vitamin K is involved in the post-translational activation by gamma-carboxylation of vitamin K dependant proteins, and in particular four proteins essential to coagulation. Food intake of vitamin K is insufficient to substitute the recycling mechanism, an efficient cycle is necessary. If VKA block the recycling mechanism, gamma-caboxylation of vitamin K dependant clotting factors becomes is not done, thus the production of the active form of these clotting factors is diminished. Consequently, the blood coagulability is affected. An important inhibition of the recycling mechanism can kill by haemorrhage, it’s with this aim that VKA are used in rodent management. Over the past three decades, a slight resistance to VKA has been observed in female rats beside male rats. Some hypothesis can explain this difference: (i) a more efficient activity of female microsomes which are responsible of the vitamin K regeneration; (ii) a faster elimination of VKA in female rats; (iii) basal concentrations and half-lives of vitamin K dependant clotting factors are higher in female rats. The main purpose of this work is to identify the origin of the resistance of female rats to VKA.Our results pinpoint significant differencies between females and males concerning the basal levels and the evolution kinetics of some vitamin K dependant clotting factors. This might explain the weaker sensibility of female rats to VKA
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  • HAL Id : tel-01425285, version 1

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Sébastien Lefebvre. Étude de l'impact du sexe sur la coagulation vitamine K dépendante chez le rat. Biochimie [q-bio.BM]. Université de Lyon, 2016. Français. ⟨NNT : 2016LYSE1231⟩. ⟨tel-01425285⟩

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