Evidence for contribution of vascular NAD(P)H oxidase to increased oxidative stress in animal models of diabetes and obesity.
Evidence for contribution of vascular NAD(P)H oxidase to increased oxidative stress in animal models of diabetes and obesity.
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DOI：
10.1016/j.freeradbiomed.2004.04.001
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发表时间：
2004-07
影响因子：
7.4
通讯作者：
T. Sonta;T. Inoguchi;H. Tsubouchi;N. Sekiguchi;Kunihisa Kobayashi;S. Matsumoto;H. Utsumi;H. Nawata
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文献类型：
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作者：
T. Sonta;T. Inoguchi;H. Tsubouchi;N. Sekiguchi;Kunihisa Kobayashi;S. Matsumoto;H. Utsumi;H. Nawata
众所周知，氧化应激在糖尿病中增强。然而，体内氧化应激的主要来源尚不清楚。在这里，我们表明血管NAD（P）H氧化酶可能是糖尿病和肥胖模型中氧化应激的主要来源。体内电子自旋共振（ESR）/自旋探针用于评价体内全身氧化应激。在糖尿病发作后2周，链脲佐菌素诱导的糖尿病大鼠中自旋探针的信号衰减率（自旋清除率; SpCR）显著增加。这种增加通过抗氧化剂α-生育酚（40 mg/kg）和超氧化物歧化酶（5000单位/kg）处理完全正常化，并且通过PKC特异性抑制剂CGP 41251（50 mg/kg）和NAD（P）H氧化酶抑制剂夹竹桃苷（5 mg/kg）处理显著抑制。与对照组相比，轻度高血糖的肥胖ob/ob小鼠（10周龄）和血糖正常的Zucker肥胖大鼠（11周龄）的SpCR均显著增加。同样，这种增加被CGP 41251和夹竹桃麻素处理抑制。胰岛素增敏剂吡格列酮（10 mg/kg）经口给药7天也使SpCR值完全正常化。这些结果表明，血管NAD（P）H氧化酶可能是糖尿病和肥胖症中氧化应激增加的主要来源。
It is well established that oxidative stress is enhanced in diabetes. However, the major in vivo source of oxidative stress is not clear. Here we show that vascular NAD(P)H oxidase may be a major source of oxidative stress in diabetic and obese models. In vivo electron spin resonance (ESR)/spin probe was used to evaluate systemic oxidative stress in vivo. The signal decay rate of the spin probe (spin clearance rate; SpCR) significantly increased in streptozotocin-induced diabetic rats 2 weeks after the onset of diabetes. This increase was completely normalized by treatment with the antioxidants α-tocopherol (40 mg/kg) and superoxide dismutase (5000 units/kg), and was significantly inhibited by treatment with a PKC-specific inhibitor, CGP41251 (50 mg/kg), and a NAD(P)H oxidase inhibitor, apocynin (5 mg/kg). Both obese ob/ob mice (10 weeks old) with mild hyperglycemia and Zucker fatty rats (11 weeks old) with normoglycemia exhibited significantly increased SpCR as compared with controls. Again, this increase was inhibited by treatment with both CGP41251 and apocynin. Oral administration of insulin sensitizer, pioglitazone (10 mg/kg), for 7 days also completely normalized SpCR values. These results suggest that vascular NAD(P)H oxidase may be a major source of increased oxidative stress in diabetes and obesity.