Hydrogen Sulfide Regulates Homocysteine-Mediated Glomerulosclerosis
Hydrogen Sulfide Regulates Homocysteine-Mediated Glomerulosclerosis
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DOI：
10.1159/000296717
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发表时间：
2010-01-01
影响因子：
4.2
通讯作者：
Tyagi, Suresh C.
中科院分区：
文献类型：
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作者：
Sen, Utpal;Munjal, Charu;Tyagi, Suresh C.
背景/目的：在这项研究中，我们测试了这样的假设：H2S 在高同型半胱氨酸血症 (HHcy) 期间调节胶原蛋白沉积、基质金属蛋白酶 (MMP) 和炎症分子，从而减轻肾小球硬化并改善肾功能。材料和方法：本研究使用 HHcy、胱硫醚β-合酶杂合子 (CBS+/-) 和野生型 (WT) 2 肾 (2K) 小鼠的遗传模型，并在饮用水中补充或不补充 NaHS（30 μmol/l，H2S 供体）8 周。为了加速与 HHcy 相关的肾损伤，还使用了类似组的未肾切除 (1K) 小鼠。结果：结果表明，WT 1K、CBS+/-2K 和 CBS+/- 1K 小鼠中 NAD(P) H 氧化酶（p47(phox) 亚基）和血压上调，同时 H2S 产生下调并降低肾小球滤过率。这些变化通过补充 H2S 得以正常化。在 WT 1K、CBS+/- 2K 和 CBS+/- 1K 小鼠中，前体和活性 MMP-2 和 -9 以及胶原蛋白表达和肾小球沉积也上调。在WT 1K、CBS+/- 2K 和CBS+/- 1K 小鼠中检测到炎症分子、细胞间细胞粘附分子-1 和血管细胞粘附分子-1 的表达增加，以及巨噬细胞浸润增加。补充 H2S 可以改善这些变化。结论：总的来说，这些结果表明 HHcy 中氧化应激的增加和 H2S 的减少会导致基质重塑和炎症，从而导致肾小球硬化和肾功能下降。版权所有 (C) 2010 S. Karger AG，巴塞尔
Background/Aims: In this study we tested the hypothesis that H2S regulates collagen deposition, matrix metalloproteinases (MMP) and inflammatory molecules during hyper-homocysteinemia (HHcy) resulting in attenuation of glomerulosclerosis and improved renal function. Materials and Methods: A genetic model of HHcy, cystathionine beta-synthase heterozygous (CBS+/-) and wild-type (WT) 2-kidney (2K) mice were used in this study and supplemented with or without NaHS (30 mu mol/l, H2S donor) in drinking water for 8 weeks. To expedite the renal damage associated with HHcy, uninephrectomized (1K) mice of similar groups were also used. Results: Results demonstrated that NAD(P) H oxidase (p47(phox) subunit) and blood pressure were upregulated in WT 1K, CBS+/-2K and CBS+/- 1K mice with downregulation of H2S production and reduced glomerular filtration rate. These changes were normalized with H2S supplementation. Both pro-and active MMP-2 and -9 and collagen protein expressions and glomerular depositions were also upregulated in WT 1K, CBS+/- 2K and CBS+/- 1K mice. Increased expressions of inflammatory molecules, intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1, as well as increased macrophage infiltration, were detected in WT 1K, CBS+/- 2K and CBS+/- 1K mice. These changes were ameliorated with H2S supplementation. Conclusion: Together, these results suggest that increased oxidative stress and decreased H2S in HHcy causes matrix remodeling and inflammation resulting in glomerulosclerosis and reduced renal function. Copyright (C) 2010 S. Karger AG, Basel