Nitrite anion therapy protects against chronic ischemic tissue injury in db/db diabetic mice in a NO/VEGF-dependent manner.
Nitrite anion therapy protects against chronic ischemic tissue injury in db/db diabetic mice in a NO/VEGF-dependent manner.
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作者：
Bir SC;Pattillo CB;Pardue S;Kolluru GK;Shen X;Giordano T;Kevil CG
亚硝酸根阴离子是一氧化氮（NO）的前体，对组织缺血/再灌注损伤、细胞保护和血管舒张具有积极作用。然而，亚硝酸盐阴离子治疗对糖尿病缺血组织血管重塑的影响仍然未知。我们研究了亚硝酸钠治疗是否改变了永久性单侧股动脉结扎的BKS-Leprdb/db小鼠的缺血性血运重建。与硝酸盐或PBS治疗相比，亚硝酸钠治疗完全恢复了缺血后肢血流量。重要的是，缺血后5天延迟亚硝酸盐治疗可以恢复老年糖尿病小鼠的缺血肢体血流。血流的恢复与缺血组织血管生成活性和细胞增殖的增加有关。此外，亚硝酸盐而不是硝酸盐治疗显着防止缺血介导的组织坏死老年小鼠。亚硝酸盐治疗显着增加缺血组织血管内皮生长因子（VEGF）蛋白的表达，亚硝酸盐介导的缺血后肢再灌注是必不可少的。亚硝酸盐显着增加缺血组织NO的生物利用度沿着减少超氧化物的形成。最后，亚硝酸盐处理也显着刺激缺氧内皮细胞增殖和迁移在高糖的存在下，在NO/VEGF依赖的方式。这些结果表明，亚硝酸盐治疗有效地刺激缺血性组织血管重塑的代谢功能障碍的设置，可能是临床上有用的。
Nitrite anion has been demonstrated to be a prodrug of nitric oxide (NO) with positive effects on tissue ischemia/reperfusion injury, cytoprotection, and vasodilation. However, effects of nitrite anion therapy for ischemic tissue vascular remodeling during diabetes remain unknown. We examined whether sodium nitrite therapy altered ischemic revascularization in BKS-Leprdb/db mice subjected to permanent unilateral femoral artery ligation. Sodium nitrite therapy completely restored ischemic hind limb blood flow compared with nitrate or PBS therapy. Importantly, delayed nitrite therapy 5 days after ischemia restored ischemic limb blood flow in aged diabetic mice. Restoration of blood flow was associated with increases in ischemic tissue angiogenesis activity and cell proliferation. Moreover, nitrite but not nitrate therapy significantly prevented ischemia-mediated tissue necrosis in aged mice. Nitrite therapy significantly increased ischemic tissue vascular endothelial growth factor (VEGF) protein expression that was essential for nitrite-mediated reperfusion of ischemic hind limbs. Nitrite significantly increased ischemic tissue NO bioavailability along with concomitant reduction of superoxide formation. Lastly, nitrite treatment also significantly stimulated hypoxic endothelial cell proliferation and migration in the presence of high glucose in an NO/VEGF-dependent manner. These results demonstrate that nitrite therapy effectively stimulates ischemic tissue vascular remodeling in the setting of metabolic dysfunction that may be clinically useful.
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影响因子：
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作者：
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DOI：
10.1016/j.beem.2008.10.015
发表时间：
2009-06-01
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通讯作者：
Mukherjee, Debabrata