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槲皮素通过 Nrf2 信号通路缓解甲状腺功能亢进症引起的肝损伤。

Quercetin alleviates hyperthyroidism-induced liver damage via Nrf2 Signaling pathway.

机构信息

The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.

出版信息

Biofactors. 2020 Jul;46(4):608-619. doi: 10.1002/biof.1626. Epub 2020 Feb 20.

DOI:10.1002/biof.1626
PMID:32078205
Abstract

Quercetin is a plant flavonoid and has antioxidative properties. In this study, we evaluated the therapeutic effect of quercetin on thyroid dysfunction in L-thyroxin (LT4)-induced hyperthyroidism rats. LT4 was used to prepare the experimental hyperthyroidism model via the intraperitoneal injection. Quercetin was injected at a series doses (5, 50, and 100 mg/kg) to LT4-induced hypothyroidism rats once a day for 14 days. The body weight and food intake were measured once a week. The levels of thyroid hormones, liver function, oxidative stress markers, and antioxidant markers were measured using commercial enzyme-linked immunosorbent assay kits. Hematoxylin-eosin staining was used to observe the thyroid tissue histological changes. The levels of nuclear and total nuclear factor erythroid 2-related factor 2 (Nrf2) were determined by western blot. The liver oxidative stress markers in LT4-induced hyperthyroidism Nrf2 knockout rats were determined to evaluate the role of Nrf2 on quercetin induced protective effects. LT4 administration increased the levels of serum triiodothyronine and thyroxine, activity of oxidative stress markers with a parallel decrease in antioxidant markers and Nrf2. However, the simultaneous administration of quercetin, reversed all these effects indicating its potential in the regulation of hyperthyroidism. Furthermore, the loss function of Nrf2 diminished these effects resulting from the quercetin application, indicating the inhibitory effects caused by the quercetin may be involved in Nrf2 signaling pathway. These results indicate that quercetin could be used to protect against experimental hyperthyroidism-induced liver damage via Nrf2 signaling pathway.

摘要

槲皮素是一种植物类黄酮,具有抗氧化特性。在这项研究中,我们评估了槲皮素对 L-甲状腺素(LT4)诱导的甲状腺功能亢进症大鼠甲状腺功能障碍的治疗作用。通过腹腔注射 LT4 制备实验性甲状腺功能亢进症模型。将槲皮素以一系列剂量(5、50 和 100mg/kg)每天注射一次至 LT4 诱导的甲状腺功能减退症大鼠,共 14 天。每周测量一次体重和食物摄入量。使用商业酶联免疫吸附测定试剂盒测量甲状腺激素、肝功能、氧化应激标志物和抗氧化标志物的水平。使用苏木精-伊红染色观察甲状腺组织的组织学变化。通过 Western blot 测定核和总核因子红细胞 2 相关因子 2(Nrf2)的水平。测定 LT4 诱导的甲状腺功能亢进症 Nrf2 敲除大鼠的肝氧化应激标志物,以评估 Nrf2 对槲皮素诱导的保护作用的作用。LT4 给药增加了血清三碘甲状腺原氨酸和甲状腺素的水平,氧化应激标志物的活性增加,同时抗氧化标志物和 Nrf2 的水平降低。然而,槲皮素的同时给药逆转了所有这些作用,表明其在调节甲状腺功能亢进症方面的潜力。此外,Nrf2 的功能丧失削弱了这些由于槲皮素应用而产生的作用,表明槲皮素引起的抑制作用可能涉及 Nrf2 信号通路。这些结果表明,槲皮素可能通过 Nrf2 信号通路用于保护实验性甲状腺功能亢进症引起的肝损伤。

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