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Endothelial relaxation mechanisms and nitrative stress are partly restored by Vitamin D3 therapy in a rat model of polycystic ovary syndrome

机译:维生素D3治疗可在多囊卵巢综合征大鼠模型中部分恢复内皮舒张机制和硝化应激

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Aims In polycystic ovary syndrome (PCOS), metabolic and cardiovascular dysfunction is related to hyperandrogenic status and insulin resistance, however, Vitamin D3 has a beneficial effect partly due to its anti-oxidant capacity. Nitrative stress is a major factor in the development of cardiovascular dysfunction and insulin resistance in various diseases. Our aim was to determine the effects of vitamin D3 in a rat model of PCOS, particularly the pathogenic role of nitrative stress. Main methods Female Wistar rats weighing 100-140 g were administered vehicle (C), dihydrotestosterone (DHT) or dihydrotestosterone plus vitamin D3 (DHT + D) (n = 10 per group). On the 10th week, acetylcholine (Ach) induced relaxation ability of the isolated thoracic aorta rings was determined. In order to examine the possible role of endothelial nitric oxide synthase (eNOS) and cyclooxygenase-2 (COX-2) pathways in the impaired endothelial function, immunohistochemical labeling of aortas with anti-eNOS and anti-COX-2 antibodies was performed. Leukocyte smears, aorta and ovary tissue sections were also immunostained with anti-nitrotyrosine antibody to determine nitrative stress. Key findings Relaxation ability of aorta was reduced in group DHT, and vitamin D3 partly restored Ach induced relaxation. eNOS labeling was significantly lower in DHT rats compared to the other two groups, however COX-2 staining showed an increment. Nitrative stress showed a significant increase in response to dihydrotestosterone, while vitamin D3 treatment, in case of the ovaries, was able to reverse this effect. Significance Nitrative stress may play a role in the pathogenesis of PCOS and in the development of the therapeutic effect of vitamin D3.
机译:目的在多囊卵巢综合症(PCOS)中,代谢和心血管功能异常与雄激素过多状态和胰岛素抵抗有关,但是,维生素D3部分具有抗氧化作用,因此具有有益作用。硝化应激是各种疾病中心血管功能障碍和胰岛素抵抗发展的主要因素。我们的目的是确定维生素D3在PCOS大鼠模型中的作用,尤其是硝化应激的致病作用。主要方法给予体重100-140 g的雌性Wistar大鼠媒介物(C),二氢睾丸激素(DHT)或二氢睾丸激素加维生素D3(DHT + D)(每组n = 10)。在第10周,确定分离的胸主动脉环的乙酰胆碱(Ach)诱导的松弛能力。为了检查内皮一氧化氮合酶(eNOS)和环氧合酶2(COX-2)通路在受损的内皮功能中的可能作用,进行了抗eNOS和抗COX-2抗体对主动脉的免疫组织化学标记。还用抗硝基酪氨酸抗体对白细胞涂片,主动脉和卵巢组织切片进行了免疫染色,以确定硝酸盐胁迫。主要发现DHT组主动脉的松弛能力降低,维生素D3部分恢复了Ach引起的松弛。与其他两组相比,DHT大鼠中的eNOS标记显着降低,但是COX-2染色显示增加。硝化应激显示对二氢睾丸激素的反应显着增加,而卵巢中的维生素D3治疗能够逆转这种作用。意义硝化应激可能在PCOS的发病机理和维生素D3治疗效果的发展中起作用。

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