Role of sulfurous mineral water and sodium hydrosulfide as potent inhibitors of fibrosis in the heart of diabetic rats
Role of sulfurous mineral water and sodium hydrosulfide as potent inhibitors of fibrosis in the heart of diabetic rats
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DOI：
10.1016/j.abb.2010.10.014
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发表时间：
2011-02-01
影响因子：
3.9
通讯作者：
Shaker, Olfat G.
中科院分区：
文献类型：
--
作者：
El-Seweidy, Mohamed M.;Sadik, Nermin A. H.;Shaker, Olfat G.
本研究探讨了高血糖可能导致糖尿病大鼠左室心肌纤维化和细胞凋亡的下游信号转导机制。还考察了硫化矿泉水或硫化氢钠(NaHS)作为可能的调节剂的效果。给链脲佐菌素(STZ)诱导的糖尿病大鼠灌胃硫酸盐矿泉水(饮水)和NaHS(14MU/kg/d，ip)，连续7周。糖尿病大鼠出现高血糖、糖化血红蛋白(HbA1C)生成过多，血清胰岛素、C-肽和胰岛素样生长因子-I(IGF-I)下降。糖尿病大鼠左室心肌核因子-kappaB、促纤维化生长因子转化生长因子-β1、基质金属蛋白-2、前胶原-1和Fas配体基因表达上调。糖尿病组中转化生长因子-β1和基质金属蛋白酶-2的表达也呈线性正相关。糖尿病大鼠心脏羟脯氨酸水平升高，氧化平衡紊乱。硫磺矿泉水和NaHS治疗可能通过改善心脏GSH水平，对抗促纤维化和促凋亡指标--核因子-kappaB的表达增强。组织病理学检查与本研究的生化和分子结果一致。建议采用硫磺矿泉水加外源性补充H_2S治疗糖尿病心肌病的新方法。(C)2010 Elsevier Inc.保留所有权利。
This study examined the downstream signaling whereby hyperglycemia may lead to myocardial fibrosis and apoptosis in the left ventricle of diabetic rats. The effects of sulfurous mineral water or sodium hydrosulfide (NaHS) as possible modulators were also examined. Sulfurous mineral water (as drinking water) and NaHS (14 mu mol/kg/day, IP) were administered for 7 week to rats with streptozotocin (STZ)-induced diabetes. Hyperglycemia, overproduction of glycated hemoglobin (HbA1C) and serum decline in insulin, C-peptide and insulin like growth factor-I (IGF-I) were observed in diabetic rats. Up-regulation of gene expressions of nuclear factor (NF-kappa B), profibrogenic growth factor such as transforming growth factor beta 1 (TGF-beta 1), matrix metalloproteniase-2 (MMP-2), procollagen-1 and Fas ligand (Fas-L) were observed in the left ventricle of diabetic rats. A linear positive correlation between TGF-beta 1 and MMP-2 was also detected in diabetic group. An increase in hydroxyproline level and a disturbance in oxidative balance were detected in heart of diabetic rats. Sulfurous mineral water and NaHS treatment possibly, by improving cardiac GSH level, counteracted the enhanced expression of NF-kappa B, the profibrogenic and apoptotic parameters. Histopathological examination was in accordance with the biochemical and molecular findings of this study. We suggest a novel therapeutic approach of sulfurous mineral water and exogenous supplementation of H2S in diabetic cardiomyopathy. (C) 2010 Elsevier Inc. All rights reserved.