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甲状腺激素三碘甲腺原氨酸输注后缺血/再灌注大鼠模型中心脏甲状腺激素脱碘酶表达的改变。

Modification of cardiac thyroid hormone deiodinases expression in an ischemia/reperfusion rat model after T3 infusion.

机构信息

Institute of Clinical Physiology, National Research Council (C.N.R.), Pisa, Italy.

出版信息

Mol Cell Biochem. 2020 Dec;475(1-2):205-214. doi: 10.1007/s11010-020-03873-w. Epub 2020 Aug 11.

Abstract

The deiodinases regulate the activation and inactivation of Thyroid hormones (TH), in both physiological and pathological conditions. The three deiodinases, DIO1, DIO2 and DIO3, have different catalytic role and cellular and tissue distribution. Aim of this study is to evaluate a rat model of regional ischemia/reperfusion (I/R), the modification of cardiac main function after the administration of 6 µg/kg/day of triiodothyronine (T3), and the associated to DIO1, DIO2 and DIO3 gene expression. We also aim to study DIO1 and DIO2 protein levels in different left ventricular regions after an ischemic event. Four groups of rats were studied: sham-operated, sham-operated + T3, I/R rats and I/R rats + T3. DIO1, DIO2 and DIO3 expression were evaluated in I/R region (AAR: area-at-risk) and in a more distant region from ischemic wound (RZ: remote zone). In I/R group, circulating free-T3 (FT3) levels were significantly decreased with respect to basal values, whereas in I/R + T3 rats, FT3 levels were comparable to basal values. In AAR of I/R + T3 rats, DIO1 and DIO2 gene expression significantly increased with respect to sham. In RZ, DIO1 and DIO3 gene expression was significantly lower in sham and I/R rats when compared to I/R + T3. In sham + T3 group, DIO1 and DIO2 gene expression was not detectable, whereas DIO3 was significantly higher than in the other three groups. The present study gives interesting new insights on DIO1, DIO2 and DIO3 in the ischemic heart and their role in relation to T3-mediated amelioration of cardiac function and structure.

摘要

脱碘酶调节甲状腺激素 (TH) 的激活和失活,无论是在生理还是病理条件下。三种脱碘酶,DIO1、DIO2 和 DIO3,具有不同的催化作用和细胞及组织分布。本研究旨在评估一种局部缺血/再灌注 (I/R) 的大鼠模型,在给予 6μg/kg/天三碘甲状腺原氨酸 (T3) 后心脏主要功能的变化,以及与 DIO1、DIO2 和 DIO3 基因表达的相关性。我们还旨在研究缺血事件后不同左心室区域中 DIO1 和 DIO2 蛋白水平。研究了四组大鼠:假手术组、假手术+T3 组、I/R 组和 I/R+T3 组。在 I/R 区域 (AAR:危险区) 和离缺血伤口更远的区域 (RZ:远区) 评估了 DIO1、DIO2 和 DIO3 的表达。与基础值相比,I/R 组循环游离三碘甲状腺原氨酸 (FT3) 水平显著降低,而 I/R+T3 组 FT3 水平与基础值相当。在 I/R+T3 大鼠的 AAR 中,DIO1 和 DIO2 基因表达与假手术组相比显著增加。在 RZ 中,与 I/R+T3 相比,假手术和 I/R 组的 DIO1 和 DIO3 基因表达显著降低。在 sham+T3 组中,DIO1 和 DIO2 基因表达无法检测到,而 DIO3 显著高于其他三组。本研究为缺血性心脏中的 DIO1、DIO2 和 DIO3 及其与 T3 介导的心脏功能和结构改善的关系提供了有趣的新见解。

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