FREE-RADICALS MEDIATE ENDOTHELIAL-CELL DYSFUNCTION CAUSED BY ELEVATED GLUCOSE
FREE-RADICALS MEDIATE ENDOTHELIAL-CELL DYSFUNCTION CAUSED BY ELEVATED GLUCOSE
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DOI：
10.1152/ajpheart.1992.263.2.h321
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发表时间：
1992-08-01
影响因子：
--
通讯作者：
COHEN, RA
中科院分区：
文献类型：
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作者：
TESFAMARIAM, B;COHEN, RA
暴露于葡萄糖浓度升高的糖尿病兔主动脉和正常主动脉内皮依赖性松弛受损，并可通过环氧化酶抑制剂加以预防。用自由基清除剂和普罗布考（1% wt/wt，一种脂溶性抗氧化剂）喂养的兔子的主动脉，研究了自由基在内皮细胞损伤中的作用。将悬挂用于测量等长张力的主动脉环在对照（5.5 mM）或升高（44 mM）葡萄糖中孵育6小时。暴露于葡萄糖升高引起的内皮依赖性乙酰胆碱松弛损伤可以通过超氧化物歧化酶、过氧化氢酶、去铁胺或别嘌呤醇来预防，并且在普罗布科尔喂养的兔子的主动脉中没有发生。同样，超氧化物歧化酶可使四氧嘧啶诱导的糖尿病家兔主动脉乙酰胆碱弛缓损伤恢复正常。黄嘌呤氧化酶产生的氧源自由基也引起乙酰胆碱松弛受损。暴露于高葡萄糖或黄嘌呤氧化酶的主动脉段导致免疫反应性前列腺素释放显著增加。这些数据表明，葡萄糖升高引起的内皮细胞功能障碍是由自由基介导的，自由基可能是通过内皮中环氧化酶催化作用的增加而产生的。用抗氧化剂治疗可以防止因葡萄糖升高引起的内皮依赖性松弛受损。
Impaired endothelium-dependent relaxation occurs in diabetic rabbit aorta and normal aorta exposed to elevated concentrations of glucose and is prevented by cyclooxypnase inhibitors. The role of free radicals in the endothelial cell impairment was examined with free radical scavengers and in aortas from rabbits fed with probucol (1% wt/wt, a lipid-soluble antioxidant). Rings of aorta suspended for measurement of isometric tension were incubated for 6 h in control (5.5 mM) or elevated (44 mM) glucose. Impairment of endothelium-dependent relaxation to acetylcholine caused by exposure to elevated glucose was prevented by superoxide dismutase, catalase, deferoxamine, or allopurinol and did not occur in aortas from probucol-fed rabbits. Similarly, impairment of acetylcholine relaxations in aortas from alloxan-induced diabetic rabbits was restored to normal by superoxide dismutase. Oxygen-derived free radicals generated by xanthine oxidase also caused impaired acetylcholine relaxations. Exposure of aortic segments to elevated glucose or to xanthine oxidase caused a significant increase in release of immunoreactive prostanoids. These data indicate that the endothelial cell dysfunction caused by elevated glucose is mediated by free radicals that are likely generated through the increased cyclooxygenase catalysis occurring in the endothelium. Treatment with antioxidants protects against impaired endothelium-dependent relaxations caused by elevated glucose.