Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, 138 Yi Xue Yuan Road, Shanghai, China.
Antioxid Redox Signal. 2010 May 1;12(9):1065-77. doi: 10.1089/ars.2009.2945.
It is not known whether H(2)S can promote angiogenesis with improvement of regional blood flow in ischemic organs. Sodium hydrosulfide (NaHS, a H(2)S donor) was administered once a day for 4 w following femoral artery ligation. Collateral vessel growth, capillary density, regional tissue blood flow, the expression of endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2) and Akt were examined during or at the end of the treatment period. NaHS treatment significantly increased collateral vessel growth, capillary density, and regional tissue blood flow in ischemic hind limb muscles compared with the controls. These effects were associated with an increase in VEGF expression in the skeletal muscles and VEGFR2 phosphorylation in the neighboring vascular endothelial cells, suggesting a role of VEGF in mediating the NaHS effects in a cell-cell interaction pattern. Moreover, NaHS treatment also resulted in an increase in Akt phosphorylation in ischemic hind limb muscles. In conclusion, our observations with NaHS strongly suggest that H(2)S is a proangiogenic factor in chronic ischemia. The proangiogenic effect of NaHS may be mediated by interaction between the upregulated VEGF in the skeletal muscle cells and the VEGFR2 as well as its downstream signaling element Akt in the vascular endothelial cells.
尚不清楚 H（2）S 是否可以通过改善缺血器官的局部血流来促进血管生成。在股动脉结扎后，每天给予硫氢化钠（H（2）S 供体）一次，持续 4 周。在治疗期间或结束时检查侧支血管生长、毛细血管密度、局部组织血流、内皮生长因子（VEGF）、VEGF 受体 2（VEGFR2）和 Akt 的表达。与对照组相比，NaHS 治疗可显著增加缺血后肢肌肉的侧支血管生长、毛细血管密度和局部组织血流。这些作用与骨骼肌中 VEGF 表达的增加和邻近血管内皮细胞中 VEGFR2 磷酸化有关，表明 VEGF 在介导 NaHS 作用的细胞-细胞相互作用模式中起作用。此外，NaHS 治疗还导致缺血后肢肌肉中 Akt 磷酸化增加。总之，我们用 NaHS 观察到的结果强烈表明 H（2）S 是慢性缺血中的促血管生成因子。NaHS 的促血管生成作用可能是通过上调的骨骼肌细胞中 VEGF 与血管内皮细胞中的 VEGFR2 及其下游信号元件 Akt 之间的相互作用介导的。
