Effect of the NAD(P)H oxidase inhibitor, apocynin, on peripheral nerve perfusion and function in diabetic rats
Effect of the NAD(P)H oxidase inhibitor, apocynin, on peripheral nerve perfusion and function in diabetic rats
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DOI：
10.1016/s0024-3205(03)00508-3
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发表时间：
2003-08-22
期刊：
影响因子：
6.1
通讯作者：
Cameron, NE
中科院分区：
文献类型：
--
作者：
Cotter, MA;Cameron, NE
血管NAD（P）H氧化酶的上调已被认为是导致若干心血管疾病状态（包括糖尿病的血管并发症）的活性氧水平升高的重要来源。先前的研究表明，抗氧化剂治疗可以纠正糖尿病大鼠受损的神经功能和血流。目的是评估NAD（P）H氧化酶在实验性糖尿病神经病变中的参与程度。为此，在未经治疗的链脲佐菌素糖尿病6周后，用NAD（P）H氧化酶、夹竹桃苷处理大鼠2周。使用了两个高剂量（15和100 mg/kg），以确保记录到最大效应。糖尿病引起坐骨神经运动传导速度降低20%，感觉隐神经功能缺损14%。夹竹桃麻素治疗分别纠正了32%和48%的这些缺陷：两种剂量的效果之间没有显著差异。氢清除微电极极谱法测定坐骨神经营养性内膜灌注。糖尿病患者的血流量和血管传导性分别减少了47%和40%。两种剂量的夹竹桃素都有类似的效果，纠正了31%的血流不足和47%的电导。因此，数据表明，NAD（P）H氧化酶有助于糖尿病大鼠的神经血管缺陷。虽然仅占糖尿病中活性氧产生升高的一部分，但该机制可为进一步研究糖尿病神经病变和血管病变提供新的治疗候选药物。(C)2003年爱思唯尔公司All rights reserved.
Upregulation of vascular NAD(P)H oxidase has been considered an important source for elevated levels of reactive oxygen species that contribute to several cardiovascular disease states, including the vascular complications of diabetes mellitus. Previous studies have shown that treatment with antioxidants corrects impaired nerve function and blood flow in diabetic rats. The aim was to assess the degree of involvement of NAD(P)H oxidase in experimental diabetic neuropathy. To this end, after 6 weeks of untreated streptozotocin-diabetes, rats were treated for 2 weeks with the NAD(P)H oxidase, apocynin. Two high doses (15 and 100 mg/kg) were used to ensure that maximal effects were registered. Diabetes caused a 20% reduction in sciatic nerve motor conduction velocity, and a 14% deficit for sensory saphenous nerve. Apocynin treatment corrected these defects by 32% and 48%, respectively: there were no significant differences between the effects of the 2 doses. Sciatic nerve nutritive endoneurial perfusion was measured by hydrogen clearance microelectrode polarography. Blood flow and vascular conductance were 47% and 40% reduced by diabetes, respectively. Both doses of apocynin had similar effects, correcting the blood flow deficit by 31% and conductance by 47%. Thus, the data show that NAD(P)H oxidase contributes to the neurovascular deficits in diabetic rats. While only accounting for part of the elevated reactive oxygen species production in diabetes, this mechanism could provide a novel therapeutic candidate for further investigation in diabetic neuropathy and vasculopathy. (C) 2003 Elsevier Inc. All rights reserved.