Department of Physiology, Harbin Medical University, Harbin, China.
Department of Physiology, Harbin Medical University, Harbin, China.
Biochem Biophys Res Commun. 2019 Jun 11;513(4):1100-1105. doi: 10.1016/j.bbrc.2019.03.182. Epub 2019 Apr 19.
Aging presents profound structural and physiological changes in the cardiovascular system. Oxidative stress, a major contributing factor during the aging process, has been involved in various age-related cardiovascular pathologies. Nevertheless, the underlying mechanism of oxidative stress in the aging heart is still unclear. This study was designed to determine whether changes in cardiac structure and function in aged rats were associated with decreases in the antioxidative defense mechanism. Young (3-month-old) and aged (24-month-old) rats were used in this study, and the differences in function, structure, antioxidative capacity and the expression of antioxidative-related proteins between the two groups were compared. By using echocardiography, we observed that compared to young rats, the left ventricular internal end-diastolic diameter (LVID; d) and left ventricular volume at diastole (LV Vol; d) were significantly increased in aged rats, while the MV E/A (E wave and A wave ratio, the ratio of peak velocity of early to late filling of mitral inflow), which represents heart diastolic function, was significantly decreased in aged rats. In addition, we observed degenerative histological modifications and an increased number of apoptotic cells in aged rats. We further detected the protein expression of catalase (CAT), glutathione synthetase (GSS), superoxide dismutase-1 (SOD-1), heme oxygenase-1 (HO-1) and NADPH: quinone oxidoreductase 1 (NQO1) in cardiac tissue. Western blot results showed that the expression of GSS was significantly decreased and that the expressions of CAT, SOD-1, and HO-1 were slightly decreased in aged rats. Immunohistochemistry results further confirmed the decreased expression of GSS, SOD-1 and NQO1 in cardiomyocytes in aged rats. Taken together, our data suggest that aging may affect the morphology and function of the heart by oxidative stress and the antioxidative defense mechanism.
衰老是心血管系统发生深刻结构和生理学变化的主要原因。氧化应激是衰老过程中的一个主要因素，它与各种与年龄相关的心血管病变有关。然而，氧化应激在衰老心脏中的潜在机制尚不清楚。本研究旨在确定衰老大鼠心脏结构和功能的变化是否与抗氧化防御机制的降低有关。本研究使用了年轻（3 个月大）和衰老（24 个月大）大鼠，比较了两组之间功能、结构、抗氧化能力和抗氧化相关蛋白表达的差异。通过超声心动图，我们观察到与年轻大鼠相比，衰老大鼠的左心室内部舒张末期直径（LVID;d）和左心室舒张末期容积（LV Vol;d）显著增加，而代表心脏舒张功能的 MV E/A（E 波和 A 波比值，即二尖瓣流入道早期和晚期充盈峰值速度之比）则显著降低。此外，我们观察到衰老大鼠的组织学退行性改变和凋亡细胞数量增加。我们进一步检测了心脏组织中过氧化氢酶（CAT）、谷胱甘肽合成酶（GSS）、超氧化物歧化酶-1（SOD-1）、血红素加氧酶-1（HO-1）和 NADPH：醌氧化还原酶 1（NQO1）的蛋白表达。Western blot 结果表明，衰老大鼠 GSS 的表达显著降低，CAT、SOD-1 和 HO-1 的表达略有降低。免疫组织化学结果进一步证实了衰老大鼠心肌细胞中 GSS、SOD-1 和 NQO1 表达的降低。综上所述，我们的数据表明，氧化应激和抗氧化防御机制可能会影响衰老心脏的形态和功能。
