高糖通过内皮型GTPCH1和NADPH氧化酶对一氧化氮和超氧阴离子的影响。
The effect of high glucose on NO and O2- through endothelial GTPCH1 and NADPH oxidase.
作者信息
Ding Qun Fang, Hayashi Toshio, Packiasamy A R Juliet, Miyazaki Asaka, Fukatsu Akiko, Shiraishi Hiroaki, Nomura Takahide, Iguchi Akihisa
机构信息
Department of Geriatrics, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Shawa-ku, Nagoya, 466-8550, Japan; Department of Geriatrics, the First University Hospital of West China University of Medical Sciences, Chengdu, China.
出版信息
Life Sci. 2004 Nov 12;75(26):3185-94. doi: 10.1016/j.lfs.2004.06.005.
Although endothelial dysfunction deteriorates diabetic angiopathy, the mechanisms are obscure. We revealed that high glucose augmented eNOS through stimulation of eNOS mRNA in cultured BAECs. NO was decreased and O2- was increased simultaneously. NOS inhibitor, inhibited O2- release, so did NADPH oxidase inhibitor. The effects were synergistic. Both intracellular BH4 level and GTPCH1 activity were decreased by high glucose, in line with decrease of GTPCH1 mRNA. HMG-CoA reductase inhibitor, atorvastatin increased GTPCH1 mRNA and activity, and BH4 level. Conclusively, high glucose leads to eNOS dysfunction by inhibiting BH4 synthesis and atorvastatin stimulate BH4 synthesis directly, and it may work as atherogenic process.
尽管内皮功能障碍会使糖尿病血管病变恶化，但其机制尚不清楚。我们发现，高糖通过刺激培养的牛主动脉内皮细胞（BAECs）中的eNOS mRNA来增强eNOS。同时，一氧化氮（NO）减少，超氧阴离子（O2-）增加。一氧化氮合酶（NOS）抑制剂抑制了O2-的释放，烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶抑制剂也有同样的效果。这些作用是协同的。高糖会使细胞内四氢生物蝶呤（BH4）水平和三磷酸鸟苷环化水解酶1（GTPCH1）活性降低，这与GTPCH1 mRNA的减少一致。羟甲基戊二酸单酰辅酶A（HMG-CoA）还原酶抑制剂阿托伐他汀增加了GTPCH1 mRNA和活性以及BH4水平。总之，高糖通过抑制BH4合成导致eNOS功能障碍，而阿托伐他汀直接刺激BH4合成，这可能在动脉粥样硬化形成过程中起作用。
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