Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Key Lab of Etiology and Epidemiology, National Health and Family Planning Commission (23618504), Harbin, 150086, Heilongjiang, China.
J Trace Elem Med Biol. 2019 Dec;56:21-30. doi: 10.1016/j.jtemb.2019.06.019. Epub 2019 Jul 13.
Selenium(Se)is an important trace element for human health. Studies have shown that selenium deficiency and low protein(Pr) intake are the primary risk factors for Keshan disease.The relationship between the cardiac malfunction induced by these two risk factors and the mitochondria-mediated apoptotic pathway is poorly understood.This study aimed to determine the effect of selenium deficiency and low protein intake on the mitochondria-mediated apoptotic pathway.
In the present study, 120 weaning Wistar rats were randomly fed one of six different diets. The myocardial tissue sections were deparaffinized in water and subjected to hematoxylin-eosin staining. Mitochondrial changes in the myocardial tissue were observed and photographed using an H-7650 Hitachi transmission electron microscope. Levels of whole blood Se were measured using hydride generation atomic fluorescence spectrometry. Whole blood glutathione peroxidase (GSH-Px) activity was measured using a glutathione peroxidase cellular activity assay kit. Malondialdehyde (MDA), total-anti-oxidizing-capability(T-AOC)and reactive oxygen species(ROS)levels in serum and myocardial tissue were measured using MDA, T-AOC and ROS kits. Apoptosis was detected by immunohistochemistry.
Experimental results showed that the selenium-deficient diet decreased serum selenium levels and GSH-PX activity, which caused severe cardiac dysfunction. Importantly, the levels of MDA and ROS in serum and myocardial tissue defects were significantly increased, where as total-anti-oxidizing-capability(T-AOC) levels were dramatically decreased as a result of the combination of selenium deficiency and low protein intake (P<0.05).The levels of cleaved caspase-9 and cleaved caspase-3 were enhanced, but the expression of B-cell lymphoma-2 (Bcl-2) was reduced (P<0.05).
Our results suggest that selenium deficiency and low protein intake can cause oxidative stress in the myocardium and induce cell apoptosis via the mitochondria-mediated pathway.
硒（Se）是人体健康的重要微量元素。研究表明，硒缺乏和低蛋白（Pr）摄入是克山病的主要危险因素。这两种危险因素引起的心脏功能障碍与线粒体介导的凋亡途径之间的关系尚不清楚。本研究旨在确定硒缺乏和低蛋白摄入对线粒体介导的凋亡途径的影响。
本研究中，将 120 只断奶 Wistar 大鼠随机分为 6 种不同饮食中的一种进行喂养。将心肌组织切片在水中脱蜡并用苏木精-伊红染色。使用 H-7650 日立透射电子显微镜观察和拍摄心肌组织中线粒体的变化。使用氢化物发生原子荧光光谱法测量全血硒水平。使用谷胱甘肽过氧化物酶细胞活性测定试剂盒测量全血谷胱甘肽过氧化物酶（GSH-Px）活性。使用 MDA、T-AOC 和 ROS 试剂盒测量血清和心肌组织中丙二醛（MDA）、总抗氧化能力（T-AOC）和活性氧（ROS）水平。通过免疫组织化学法检测细胞凋亡。
实验结果表明，缺硒饮食降低了血清硒水平和 GSH-PX 活性，导致严重的心脏功能障碍。重要的是，由于硒缺乏和低蛋白摄入的结合，血清和心肌组织缺陷中的 MDA 和 ROS 水平显著增加，而总抗氧化能力（T-AOC）水平显著降低（P<0.05）。裂解的胱天蛋白酶-9 和裂解的胱天蛋白酶-3 的水平升高，但 B 细胞淋巴瘤-2（Bcl-2）的表达减少（P<0.05）。
我们的结果表明，硒缺乏和低蛋白摄入可导致心肌氧化应激，并通过线粒体介导的途径诱导细胞凋亡。
