Huang Pan, Shen Zhizhou, Yu Wen, Huang Yaqian, Tang Chaoshu, Du Junbao, Jin Hongfang
Department of Pediatrics, Peking University First Hospital Beijing, China.
Department of Physiology and Pathophysiology, Peking University Health Science Centre Beijing, China.
Front Pharmacol. 2017 Mar 16;8:128. doi: 10.3389/fphar.2017.00128. eCollection 2017.
The study aimed to examine the protective effect of hydrogen sulfide (HS) on high-salt-induced oxidative stress and myocardial hypertrophy in salt-sensitive (Dahl) rats. Thirty male Dahl rats and 40 SD rats were included in the study. They were randomly divided into Dahl control (Dahl + NS), Dahl high salt (Dahl + HS), Dahl + HS + NaHS, SD + NS, SD + HS, SD + HS + NaHS, and SD + HS + hydroxylamine (HA). Rats in Dahl + NS and SD + NS groups were given chow with 0.5% NaCl and 0.9% normal saline intraperitoneally daily. Myocardial structure, α-myosin heavy chain (α-MHC) and β-myosin heavy chain (β-MHC) expressions were determined. Endogenous myocardial HS pathway and oxidative stress in myocardial tissues were tested. Myocardial HS pathway was downregulated with myocardial hypertrophy featured by increased heart weight/body weight and cardiomyocytes cross-sectional area, decreased α-MHC and increased β-MHC expressions in Dahl rats with high-salt diet (all < 0.01), and oxidative stress in myocardial tissues was significantly activated, demonstrated by the increased contents of hydroxyl radical, malondialdehyde and oxidized glutathione and decreased total antioxidant capacity, carbon monoxide, catalase, glutathione, glutathione peroxidase, superoxide dismutase (SOD) activities and decreased SOD1 and SOD2 protein expressions ( < 0.05, < 0.01). However, HS reduced myocardial hypertrophy with decreased heart weight/body weight and cardiomyocytes cross-sectional area, increased α-MHC, decreased β-MHC expressions and inhibited oxidative stress in myocardial tissues of Dahl rats with high-salt diet. However, no significant difference was found in HS pathway, myocardial structure, α-MHC and β-MHC protein and oxidative status in myocardial tissues among SD + NS, SD + HS, and SD + HS + NaHS groups. HA, an inhibitor of cystathionine β-synthase, inhibited myocardial HS pathway ( < 0.01), and stimulated myocardial hypertrophy and oxidative stress in SD rats with high-salt diet. Hence, HS inhibited myocardial hypertrophy in high salt-stimulated Dahl rats in association with the enhancement of antioxidant capacity, thereby inhibiting oxidative stress in myocardial tissues.
该研究旨在探讨硫化氢（HS）对盐敏感（Dahl）大鼠高盐诱导的氧化应激和心肌肥大的保护作用。研究纳入了30只雄性Dahl大鼠和40只SD大鼠。它们被随机分为Dahl对照组（Dahl + NS）、Dahl高盐组（Dahl + HS）、Dahl + HS + NaHS组、SD + NS组、SD + HS组、SD + HS + NaHS组以及SD + HS + 羟胺（HA）组。Dahl + NS组和SD + NS组的大鼠每天给予含0.5%氯化钠的饲料并腹腔注射0.9%生理盐水。测定心肌结构、α-肌球蛋白重链（α-MHC）和β-肌球蛋白重链（β-MHC）的表达。检测心肌组织内源性HS途径和氧化应激情况。高盐饮食的Dahl大鼠心肌HS途径下调，表现为心脏重量/体重增加、心肌细胞横截面积增大、α-MHC降低、β-MHC表达增加（均P < 0.01），心肌组织氧化应激显著激活，表现为羟自由基、丙二醛和氧化型谷胱甘肽含量增加，总抗氧化能力、一氧化碳、过氧化氢酶、谷胱甘肽、谷胱甘肽过氧化物酶、超氧化物歧化酶（SOD）活性降低以及SOD1和SOD2蛋白表达降低（P < 0.05，P < 0.01）。然而，HS减轻了高盐饮食的Dahl大鼠的心肌肥大，表现为心脏重量/体重和心肌细胞横截面积降低、α-MHC增加、β-MHC表达降低，并抑制了心肌组织的氧化应激。然而，SD + NS组、SD + HS组和SD + HS + NaHS组在HS途径、心肌结构、α-MHC和β-MHC蛋白以及心肌组织氧化状态方面未发现显著差异。HA是胱硫醚β-合酶的抑制剂，抑制了心肌HS途径（P < 0.01），并在高盐饮食的SD大鼠中刺激了心肌肥大和氧化应激。因此，HS通过增强抗氧化能力抑制了高盐刺激的Dahl大鼠的心肌肥大，从而抑制了心肌组织的氧化应激。
