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Bradykinin B2 receptors -- a target in diabetic nephropathy.

机译:缓激肽B2受体-糖尿病肾病的靶标。

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Diabetic nephropathy is the leading cause of chronic renal failure in westernized countries. The polymorphism in angiotensin-converting enzyme (ACE), which leads to higher than normal levels of this enzyme, is a predictor of nephropathy in patients with diabetes. As increasing the levels of ACE by approximately 50% in this polymorphism is only calculated to increase the levels of angiotensin II by < 5%, whereas the levels of bradykinin will decrease by 20%, bradykinin may be nephroprotective. In diabetic mice without bradykinin B2 receptors, the only parameter that is altered compared with the diabetic mouse, is that the nephropathy is worse. Thus, in diabetic mice without a bradykinin receptor (Bdrb2(-/-)Ins2(+/C96Y)), compared with diabetic mice (Bdrb2(+/+)/Ins2(+/C96Y)), there is a greater kidney weight, increased urinary albumin output, and glomeruli mesangial sclerosis. In addition to reducing the levels of angiotensin II, vasopeptidase inhibitors increase the level of bradykinin. A vasopeptidase inhibitor (AVE7688) has been shown to prevent nephropathy developing and to ameliorate it once it has developed in Zucker diabetic rats. The nephroprotective effects (reduced albumin secretion and reduced kidney damage) of AVE7688 in Zucker diabetic rats were partially prevented by the bradykinin B2 receptor antagonist icatibant. These data establish that stimulation of bradykinin B2 receptors is a target in diabetic nephropathy.
机译:在西方国家,糖尿病肾病是慢性肾功能衰竭的主要原因。血管紧张素转换酶(ACE)的多态性导致该酶的水平高于正常水平,是糖尿病患者肾病的预测指标。由于在这种多态性中将ACE的水平提高约50%只能使血管紧张素II的水平提高<5%,而缓激肽的水平将降低20%,因此缓激肽可能具有肾脏保护作用。在没有缓激肽B2受体的糖尿病小鼠中,与糖尿病小鼠相比唯一改变的参数是肾病更严重。因此,在没有缓激肽受体(Bdrb2(-/-)Ins2(+ / C96Y))的糖尿病小鼠中,与糖尿病小鼠(Bdrb2(+ / +)/ Ins2(+ / C96Y))相比,肾脏的肾脏重量更大,尿白蛋白输出增加和肾小球系膜硬化。除了降低血管紧张素II的水平外,血管肽酶抑制剂还增加了缓激肽的水平。血管肽酶抑制剂(AVE7688)已显示可预防肾病并在Zucker糖尿病大鼠中一旦发展便会改善。缓激肽B2受体拮抗剂icatibant可以部分预防AVE7688在Zucker糖尿病大鼠中的肾保护作用(减少白蛋白分泌和减少肾脏损害)。这些数据证实,缓激肽B2受体的刺激是糖尿病性肾病的靶标。

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