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雌激素增加卵巢切除大鼠心肌中胱硫醚-γ-裂解酶的表达,减少炎症和氧化应激。

Estrogens increase cystathionine-γ-lyase expression and decrease inflammation and oxidative stress in the myocardium of ovariectomized rats.

机构信息

From the 1Department of Physiology, Second Military Medical University, Shanghai, China; and 2School of Kinesiology, Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai, China.

出版信息

Menopause. 2013 Oct;20(10):1084-91. doi: 10.1097/GME.0b013e3182874732.

Abstract

OBJECTIVE

Hydrogen sulfide (H2S), generated in the myocardium predominantly via cystathionine-γ-lyase (CSE), is cardioprotective. The objectives of the present study were to investigate the effects of estrogens on CSE expression and H2S generation in the myocardium and to examine whether serum 17β-estradiol (E2) level is associated with CSE activity and H2S generation and whether H2S or E2 level is associated with proinflammatory cytokines and oxidative stress status.

METHODS

Ovariectomized Sprague-Dawley rats received subcutaneous E2 (30 μg/kg/d) or vehicle for 12 weeks. At the end of the 12-week treatment, CSE expression, H2S generation, reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, total antioxidant capacity (T-AOC), superoxide dismutase (SOD) activity, catalase (CAT) activity, interleukin (IL)-6 concentration, and tumor necrosis factor-α (TNF-α) concentration in the left ventricle were determined.

RESULTS

E2 increased CSE expression and H2S generation in the myocardium of ovariectomized rats. H2S production rate and serum E2 were positively correlated. E2 increased GSH/GSSG ratio, T-AOC, CAT, and SOD activity but decreased IL-6 and TNF-α levels. Serum E2 level was positively correlated with GSH/GSSG ratio, T-AOC, CAT, and SOD activity, and inversely correlated with IL-6 and TNF-α levels. H2S generation rate was positively correlated with T-AOC and GSH/GSSG ratio, and inversely correlated with IL-6 and TNF-α levels.

CONCLUSIONS

E2 increases CSE expression and endogenous H2S generation in the myocardium. The effects of E2 are associated with decreased oxidative stress and inflammatory status. Our data suggest that estrogens might exert cardioprotective effects through up-regulation of CSE expression and H2S generation.

摘要

目的

心肌中主要通过胱硫醚-γ-裂解酶(CSE)生成的硫化氢(H2S)具有心脏保护作用。本研究的目的是探讨雌激素对心肌中 CSE 表达和 H2S 生成的影响,以及血清 17β-雌二醇(E2)水平是否与 CSE 活性和 H2S 生成相关,以及 H2S 或 E2 水平是否与促炎细胞因子和氧化应激状态相关。

方法

去卵巢 Sprague-Dawley 大鼠接受皮下 E2(30μg/kg/d)或载体治疗 12 周。在 12 周治疗结束时,测定左心室中 CSE 表达、H2S 生成、还原型谷胱甘肽/氧化型谷胱甘肽(GSH/GSSG)比值、总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)活性、过氧化氢酶(CAT)活性、白细胞介素(IL)-6 浓度和肿瘤坏死因子-α(TNF-α)浓度。

结果

E2 增加了去卵巢大鼠心肌中的 CSE 表达和 H2S 生成。H2S 生成率与血清 E2 呈正相关。E2 增加了 GSH/GSSG 比值、T-AOC、CAT 和 SOD 活性,但降低了 IL-6 和 TNF-α 水平。血清 E2 水平与 GSH/GSSG 比值、T-AOC、CAT 和 SOD 活性呈正相关,与 IL-6 和 TNF-α 水平呈负相关。H2S 生成率与 T-AOC 和 GSH/GSSG 比值呈正相关,与 IL-6 和 TNF-α 水平呈负相关。

结论

E2 增加了心肌中 CSE 的表达和内源性 H2S 的生成。E2 的作用与降低氧化应激和炎症状态有关。我们的数据表明,雌激素可能通过上调 CSE 表达和 H2S 生成发挥心脏保护作用。

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