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Effet de l’hypoxie intermittente et de l’entraînement physique intensif sur la structure et la fonction du tissu musculaire chez le rat.

Abstract : Obstructive sleep apnea syndrome (OSAS) is a chronic disease characterized by repeated interruptions of breathing during sleep due to the temporary closure of the upper airway. Its prevalence increases with the increasing in prevalence of obesity, especially in developed countries.Chronic intermittent hypoxia (IH) resulting from this transient closure of the upper airway is one of the major consequences of OSAS and is responsible of most of the complications related to this pathology, including hypertension, myocardial infarction, atherosclerosis and more generally cardiovascular remodeling.On the other hand, intensive physical training(IT) is well known to have benefits on cardiovascular system, thus we hypothesize that physical training can reverse the deleterious effects of IH on reactivity and vascular remodeling as well as intracellular calcium signaling in muscle cells.To answer this question, we chose the rat as an animal model to study the potential effect of IT in the prevention and reversal of deleterious (IH) effects in terms of reactivity and calcium signaling in muscle tissue.Rats were exposed for 21 days to intermittent hypoxia and housed in cages specially equipped to maintain an airflow alternating between 21% and 5% PO2 in cages containing hypoxic rats and 21% PO2 in cages containing the control rats. During the last two weeks of exposure to IH, a group of hypoxic rats and one of the normoxic rats underwent IT sessions on a treadmill at a speed of 16m / min to 30m / min.Physiological parameters were measured (blood pressure, heart rate, hematocrit), the aorta was removed to study the vascular reactivity, then vascular smooth muscle cells were removed and cultured to study calcium signaling by EPIfluorescence microscopy. Finally, the genes coding for the key mediators of the calcium signaling: RyR1, RyR2 RyR3, (ryanodine receptors), TRPV4 (transient receptor potential channel), SERCA1, SERCA2 (Sarco / Endoplasmic Reticulum Ca2 + -ATPase) and IP3R1 , 5-Trisphosphate Receptor) in various vascular and skeletal tissues were studied at the molecular level as mRNA by Q-PCR or as protein by Western Blot.Our results show that IH induces a significant increase in blood pressure and hematocrit and a decrease in acetylcholine-induced aortic relaxation pre-contracted with phenylnephrine. This was consistent with our observation that HI increases the level of intracellular calcium in cultured aortic smooth muscle. On the other hand, IT induced a significant decrease in hematocrit and aortic vasoconstriction induced by phenylnephrine and endothelial-1, consistant with the observation that IT reduces the IH-N difference in the calcium response. On the molecular scale, IH induces a significant increase in the expression of RyR1, RyR2, RyR3, SERCA1, SERCA2, TRPV4 and IP3R1 at the mRNA level in the tissues of all groups with a greater amount of RyR1,RyR2,& RyR3 higher in IH tissue of smooth muscles (mainly in the thoracic and abdominal aorta) and SERCA1 (9-fold higher in IH tissues) and SERCA2 (10-fold higher in IH tissues) in the skeletal muscles (Gastrocnemius, plantaris and soléus). In addition, IH induces a significant increase in RYR1, RYR2 and TRPV4 at the protein level in the thoracic and abdominal aorta; And IT reduces the difference in expression between animals N and IH.Our results suggest that IT is a promising, non-pharmacological or complementary treatment for limiting cardiovascular complications induced by IH and muscle remodeling in patients with OSAS.
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Submitted on : Monday, May 6, 2019 - 2:56:08 PM
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Zeinab El Dirani. Effet de l’hypoxie intermittente et de l’entraînement physique intensif sur la structure et la fonction du tissu musculaire chez le rat.. Médecine humaine et pathologie. Université Grenoble Alpes; Université Libanaise, 2018. Français. ⟨NNT : 2018GREAV067⟩. ⟨tel-02121318⟩



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