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首页> 外文期刊>Diabetes care >Platelet redox balance in diabetic patients with hypertension improved by n-3 fatty acids
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Platelet redox balance in diabetic patients with hypertension improved by n-3 fatty acids

机译:n-3脂肪酸改善糖尿病高血压患者的血小板氧化还原平衡

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OBJECTIVE-Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing cardiovascular disease, largely as a result of defective production of cardioprotective nitric oxide and a concomitant rise in oxidative stress. Dietary interventions that could reverse this trend would be extremely beneficial. Here we investigated whether dietary n-3 polyunsaturated fatty acid (n-3 PUFA) supplementation positively affected platelet nitroso-redox imbalance. RESEARCH DESIGN AND METHODS-We randomized hypertensive T2DM patients (T2DM HT; n = 22) and age-and-sex matched hypertensive study participants without diabetes (HT alone; n = 23) in a double-blind, crossover fashion to receive 8 weeks of n-3 PUFAs (1.8 g eicosapentaenoic acid and 1.5 g docosahexaenoic acid) or identical olive oil capsules (placebo), with an intervening 8-week washout period. Platelet nitrite and superoxide were measured and compared before and after treatment; 8-isoprostane was determined by ELISA and subcellular compartmentalization of the NAD(P)H oxidase subunit p47-phox examined by Western blotting. RESULTS-The n-3 PUFA supplementation reduced 8-isoprostane and superoxide levels in platelets from T2DM HT, but not HT alone, participants, without effect on nitrite production. This coincided with a significant decrease in p47-phox membrane localization and a similar reduction in superoxide to that achieved with apocynin. At baseline, a subcohort of T2DM HT and HT alone participants showed evidence of nitric oxide synthase (NOS)-derived superoxide production, indicating defective enzymatic activity. This was reversed significantly in T2DM HT participants after treatment, demonstrating improved NOS function. CONCLUSIONS-Our finding that n-3 PUFAs diminish platelet superoxide production in T2DM HT patients in vivo suggests a therapeutic role for these agents in reducing the vascularderived oxidative stress associated with diabetes. ? 2013 by the American Diabetes Association.
机译:目标2型糖尿病(T2DM)的患者罹患心血管疾病的风险增加,这在很大程度上是由于心脏保护性一氧化氮产生缺陷以及氧化应激的同时升高所致。可以逆转这一趋势的饮食干预将是极其有益的。在这里,我们调查了膳食中的n-3多不饱和脂肪酸(n-3 PUFA)补充是否对血小板亚硝基-氧化还原失衡有积极影响。研究设计和方法-我们以双盲,交叉的方式将高血压的T2DM患者(T2DM HT; n = 22)和年龄和性别匹配的无糖尿病的高血压研究参与者(仅HT; n = 23)随机分组以接受8周取n-3 PUFA(1.8克二十碳五烯酸和1.5克二十二碳六烯酸)或相同的橄榄油胶囊(安慰剂),中间有8周的清除期。治疗前后分别测量并比较了血小板亚硝酸盐和超氧化物。通过ELISA确定8-异前列腺素,并通过蛋白质印迹检查NAD(P)H氧化酶亚基p47-phox的亚细胞区室化。结果-n-3 PUFA补充剂可降低参与者的T2DM HT血小板中的8-异前列腺素和超氧化物水平,但单独使用HT不能降低亚硝酸盐的产生。这与p47-phox膜定位的显着降低以及超氧化物歧化酶与载脂蛋白的相似降低相吻合。在基线时,T2DM HT和单独的HT参与者的一个亚组显示了一氧化氮合酶(NOS)衍生的超氧化物产生的证据,表明酶活性有缺陷。在治疗后,T2DM HT参与者的这种情况得到了明显的逆转,表明NOS功能得到了改善。结论-我们的发现发现,n-3 PUFA减少了T2DM HT患者体内的血小板超氧化物生成,提示这些药物在减少与糖尿病相关的血管源性氧化应激中具有治疗作用。 ? 2013年由美国糖尿病协会颁发。

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