Estrogens increase cystathionine--lyase expression and decrease inflammation and oxidative stress in the myocardium of ovariectomized rats
Estrogens increase cystathionine--lyase expression and decrease inflammation and oxidative stress in the myocardium of ovariectomized rats
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DOI：
10.1097/gme.0b013e3182874732
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发表时间：
2013-10
期刊：
影响因子：
--
通讯作者：
Xiaoyan Zhu;Zhiping Tang;Binhai Cong;Jiankui Du;Changnan Wang;Long Wang;X. Ni;Jianqiang Lu
中科院分区：
文献类型：
--
作者：
Xiaoyan Zhu;Zhiping Tang;Binhai Cong;Jiankui Du;Changnan Wang;Long Wang;X. Ni;Jianqiang Lu
目的硫化氢（H2S）主要通过心肌中的胱硫醚裂解酶（CSE）产生，具有心脏保护作用。本研究的目的是研究雌激素对心肌中CSE表达和H2S生成的影响，并检查血清17-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。方法去势SD大鼠皮下注射E2（30 g/kg/d）或溶剂12周。在12周治疗结束时，测定左心室CSE表达、H2S产生、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（TNF-α）浓度。结果E2可增加去卵巢大鼠心肌CSE表达和H2S生成。H2S产生率与血清E2呈正相关。E_2可提高GSH/GSSG比值、T-AOC、CAT和SOD活性，降低IL-6和TNF-α水平。血清E2水平与GSH/GSSG比值、T-AOC、CAT、SOD活性呈正相关，与IL-6、TNF-α水平呈负相关。H_2S生成率与T-AOC、GSH/GSSG比值呈正相关，与IL-6、TNF-α水平呈负相关。结论E2增加心肌CSE表达和内源性H2S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生成来发挥心脏保护作用。
Objective Hydrogen sulfide (H2S), generated in the myocardium predominantly via cystathionine--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 17-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 g/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- (TNF-) 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- 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- levels. H2S generation rate was positively correlated with T-AOC and GSH/GSSG ratio, and inversely correlated with IL-6 and TNF- 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.