Increased superoxide contributes to enhancement of vascular contraction in Ins2(Akita) diabetic mice, an autosomal dominant mutant model.
Increased superoxide contributes to enhancement of vascular contraction in Ins2(Akita) diabetic mice, an autosomal dominant mutant model.
复制标题
超氧化物的增加有助于增强 Ins2（秋田）糖尿病小鼠（一种常染色体显性突变模型）的血管收缩。
DOI：
10.1111/j.1440-1681.2007.04756.x
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发表时间：
2008
影响因子：
2.9
通讯作者：
Chen,AlexF
中科院分区：
文献类型：
--
作者：
Yang,Xiang-Qun;Wang,Ying-Ying;Chen,AlexF
1 据报道，超氧化物与糖尿病的血管功能障碍有关。 Ins2Akitamouse 是一种常染色体显性突变糖尿病模型，可以作为化学糖尿病原诱导的 1 型糖尿病小鼠模型的良好替代品。本研究的目的是利用这种新的糖尿病模型研究超氧化物对血管功能障碍的作用。2与年龄匹配的正常 C57BL/6 小鼠相比，Ins2Akita 糖尿病小鼠的动脉超氧化物、脂质过氧化产生量（分别为 1.2 ± 0.1 vs17.4 ± 1.9 mmol/mg 组织；P < 0.01）和血浆脂质过氧化产生量（分别为 0.08 ± 0.02 与 0.40 ± 0.03 mmol/L；P < 0.01）增加。同时，主动脉和/或血浆中血管粘附分子-1、E-选择素和单核细胞趋化蛋白-1的表达升高。3Ins2Akita糖尿病小鼠的颈动脉向U46619的收缩力与对照小鼠相比显着增强（P<0.05）。 Tempol（超氧化物清除剂）、夹竹桃麻素（NADPH 氧化酶抑制剂）和别嘌呤醇（黄嘌呤氧化酶抑制剂）不仅能减少颈动脉中的超氧化物，而且还能抑制 Ins2Akita 糖尿病小鼠 U46619 的动脉收缩。吲哚美辛（一种环加氧酶抑制剂）和白屈菜红碱（一种蛋白激酶 C 抑制剂）也能抑制增强的血管收缩。4这些结果表明，不同来源产生的动脉超氧化物增加可能会增强 Ins2Akita 糖尿病小鼠的颈动脉收缩。
1Superoxide has been reported to be involved in vascular dysfunction in diabetes. The Ins2Akitamouse is an autosomal dominant mutant diabetic model that can serve as an excellent substitute for the Type 1 diabetic mouse model induced by chemical diabetogens. The purpose of the present study was to investigate the role of superoxide on vascular dysfunction using this new diabetic model.2Compared with age‐matched normal C57BL/6 mice, in Ins2Akitadiabetic mice arterial superoxide, lipid peroxidation production (1.2 ± 0.1vs17.4 ± 1.9 mmol/mg tissue, respectively;P< 0.01) and plasma lipid peroxidation production (0.08 ± 0.02vs0.40 ± 0.03 mmol/L, respectively;P< 0.01) were increased. Meanwhile, expression of vascular adhesion molecule‐1, E‐selectin and monocyte chemoattractant protein‐1 in the aorta and/or plasma was elevated.3The contraction of carotid arteries to U46619 in Ins2Akitadiabetic mice was significantly enhanced compared with control mice (P< 0.05). Tempol (a scavenger of superoxide), apocynin (an inhibitor of NADPH oxidase) and allopurinol (an inhibitor of xanthine oxidase) all not only decreased superoxide in carotid arteries, but also suppressed arterial contractions to U46619 in Ins2Akitadiabetic mice. Indomethacin, an inhibitor of cyclo‐oxygenase, and chelerythrine, an inhibitor of protein kinase C, also suppressed the enhanced vascular contraction.4These results suggest that increased arterial superoxide generated from diverse sources may potentiate the contractions of carotid arteries in Ins2Akitadiabetic mice.