Abstract
BackgroundThe goal of this study is to determine if Rhodiola Crenulata (RC) has protective effects on mice hearts with severe sleep apnea model.MethodsSixty-four C57BL/6 J mice 5–6 months old were distributed into 4 groups i.e. Control group (21 % O2, 24 h per day, 8 weeks, n = 16); Hypoxia group (Hypoxia: 7 % O2 60 s, 20 % O2 alternating 60 s, 8 h per day, 8 weeks, n = 16); Hypoxia + 90RC and Hypoxia + 270RC group (Hypoxia for 1st 4 weeks and hypoxia pretreated 90 mg/Kg and 270 mg/Kg Rhodiola Crenulata by oral gavage per day for 2nd 4 weeks, each n = 16). Excised hearts from 4 groups of mice were analyzed for heart weight index changes using H&E staining, TUNEL-positive assays and Western Blotting protein.ResultsCardiac widely dispersed TUNEL-positive apoptotic cells in mice hearts were less in Hypoxia + RC90 and Hypoxia + RC270 than those in Hypoxia. Compared with Hypoxia, the protein levels of Fas ligand, Fas death receptors, Fas-Associated Death Domain (FADD), activated caspase 8, and activated caspase 3 (Fas dependent apoptotic pathways) were decreased in Hypoxia + RC90, Hypoxia + RC270. The protein levels of Bad, Bax, t-Bid, activated caspase 9, activated caspase 3 (mitochondria dependent apoptotic pathway) were less in Hypoxia + RC90, Hypoxia + RC270 than those in hypoxia. The protein levels of Bcl2, Bcl-xL, p-Bad (Bcl2-realted anti-apoptotic pathway) and VEGF, p-PI3k, p-AKT (VEGF-related pro-survival pathway) were higher in Hypoxia + RC90, Hypoxia + RC270 than those in hypoxia.ConclusionsOur findings suggest that Rhodiola Crenulata have protective effects on chronic intermittent hypoxia-induced cardiac widely dispersed apoptosis via Fas-dependent and mitochondria-dependent apoptotic and VEGF-related pro-survival pathway.
Highlights
Obstructive sleep apnea (OSA) is a sleep breathing disorder characterized by intermittent upper airway collapse during sleep and leads to sleep fragmentation [1]
Body weight and cardiac characteristics Body weight, whole heart weight, left ventricular weight in the Hypoxia, the Hypoxia + RC90, and the Hypoxia + RC270 groups were similar to the Control group (Table 1)
Whole heart weight (WHW), left ventricular weight (LVW), whole heart weight normalized by tibia length (WHW/Tibia), left ventricular weight normalized by tibia length (LVW/Tibia) in the Hypoxia + RC90, and the Hypoxia + RC270 groups were similar to the Control group
Summary
Obstructive sleep apnea (OSA) is a sleep breathing disorder characterized by intermittent upper airway collapse during sleep and leads to sleep fragmentation [1]. Obstructive sleep apnea is often associated with cardiovascular diseases including coronary artery diseases and congestive heart failure [2, 3]. Rhodiola Crenulata, a species of Rhodiola, was often applied to avoid altitude sickness [7, 8] and it have been reported to decreased hypoxia-induced oxidative stress [8, 9]. Rhodiola increased stress resistance, cardiopulmonary protection, and cardiovascular function [7]. Salidroside showed protection through chronic intermittent hypoxia-induced Fas-dependent and mitochondriadependent apoptotic pathways on mice hearts [5]. The effect of Rhodiola Crenulata on cardiovascular health is still unclear. The goal of this study is to determine if Rhodiola Crenulata (RC) has protective effects on mice hearts with severe sleep apnea model
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