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131I 诱导的甲状腺功能减退症对大鼠一氧化氮(NO)、白细胞介素 6(IL-6)、肿瘤坏死因子α(TNF-α)、总一氧化氮合酶(NOS)活性和 NOS 同工型表达水平的影响。

The effect of 131I-induced hypothyroidism on the levels of nitric oxide (NO), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), total nitric oxide synthase (NOS) activity, and expression of NOS isoforms in rats.

机构信息

Department of Nuclear Medicine, The Fuling Central Hospital of Chongqing, Chongqing, China.

出版信息

Bosn J Basic Med Sci. 2018 Nov 7;18(4):305-312. doi: 10.17305/bjbms.2018.2350.

DOI:10.17305/bjbms.2018.2350
PMID:29579409
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6252099/
Abstract

Accumulating evidence has shown that hypothyroidism affects the cardiovascular system, significantly increasing the incidence of cardiovascular diseases. In the present study we investigated the effect of radioactive iodine (I-131)-induced hypothyroidism on several parameters of vascular function, such as nitric oxide (NO), total nitric oxide synthase (NOS) activity and expression of NOS isoforms, as well as on interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) as indicators of inflammation, in rats. A dose of 150 µCi of 131-I was determined as optimal for establishing the model of hypothyroidism in rats. After administration of 131-I, at the end of month 1, 2, and 4 (n = 3 for each time point), NO, IL-6, and TNF-α in the serum and total NOS activity in the aorta were determined in 150 µCi group, compared to controls. The mRNA and protein expression of endothelial, neuronal, and inducible NOS (eNOS, nNOS, and iNOS) in the rat aorta was also estimated, using quantitative reverse transcription polymerase chain reaction and Western blot, respectively. The levels of IL-6 and TNF-α increased in 150 µCi group; the results were significant at the end of month 2 and 4 for IL-6, and at all time points for TNF-α. The levels of NO decreased significantly at the end of month 2 and 4 in 150 µCi group. The total NOS activity increased significantly in 150 µCi group, at all three time points. Significant changes in the mRNA and protein expression of all three NOS isoforms were observed in 150 µCi group compared to controls. NO, IL-6, TNF-α levels and NOS activity and expression are altered in hypothyroid state, and the underlying mechanism should be further investigated.

摘要

越来越多的证据表明,甲状腺功能减退症会影响心血管系统,显著增加心血管疾病的发病率。在本研究中,我们研究了放射性碘(I-131)诱导的甲状腺功能减退症对血管功能的几个参数的影响,如一氧化氮(NO)、总一氧化氮合酶(NOS)活性和 NOS 同工型的表达,以及白细胞介素 6(IL-6)和肿瘤坏死因子α(TNF-α)作为炎症的指标,在大鼠中。确定 150µCi 的 131-I 剂量是建立大鼠甲状腺功能减退症模型的最佳剂量。在给予 131-I 后,在第 1、2 和 4 个月结束时(每个时间点 n = 3),与对照组相比,测定 150µCi 组大鼠血清中 NO、IL-6 和 TNF-α以及主动脉中的总 NOS 活性。还使用定量逆转录聚合酶链反应和 Western blot 分别估计了大鼠主动脉中内皮型、神经元型和诱导型 NOS(eNOS、nNOS 和 iNOS)的 mRNA 和蛋白表达。在 150µCi 组中,IL-6 和 TNF-α 的水平增加;在第 2 和 4 个月结束时,IL-6 的结果显著,而 TNF-α 在所有时间点都显著。在 150µCi 组中,NO 的水平在第 2 和 4 个月结束时显著降低。在 150µCi 组中,总 NOS 活性在所有三个时间点均显著增加。与对照组相比,150µCi 组三种 NOS 同工型的 mRNA 和蛋白表达均发生显著变化。在甲状腺功能减退状态下,NO、IL-6、TNF-α 水平以及 NOS 活性和表达均发生改变,其潜在机制应进一步研究。

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