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Review Article

L-肌肽及其衍生物作为预防和治疗糖尿病血管并发症的新疗法

卷 27, 期 11, 2020

页: [1744 - 1763] 页: 20

弟呕挨: 10.2174/0929867326666190711102718

价格: $65

摘要

血管并发症是糖尿病最严重的表现之一。动脉粥样硬化是糖尿病患者生活质量和预期寿命降低的主要原因，而糖尿病肾病和视网膜病是终末期肾脏疾病和失明的最常见原因。预防血管并发症的有效治疗方法应抵消损伤的机制。其中，高级糖化（AGEs）和脂氧化（ALEs）终产物的毒性作用是这些后遗症的公认原因。 L-肌肽（β-丙氨酰-组氨酸）可作为AGE / ALE前体反应性羰基物种（RCS）的淬灭剂，后者是糖和脂质的氧化和非氧化修饰形式的高反应性醛。一致地，发现L-肌肽在几种疾病模型中是有效的，其中糖/脂氧化起着重要的致病作用。不幸的是，在人类中，L-肌肽被血清肌肽酶迅速失活。因此，寻找Lcarnosine的抗肌苷酶抗性衍生物代表了针对羰基应激依赖性疾病，特别是糖尿病性血管并发症的合适策略。在这篇综述中，我们提出并讨论了有关L-肌肽及其衍生物预防糖尿病和代谢综合征啮齿动物模型中的血管并发症的功效的可用数据。我们还讨论了遗传发现，为肌肽酶/ L-肌肽系统参与糖尿病性肾病的风险提供了证据，并为在人类疾病中偏爱使用肌肽酶抗性化合物提供了证据。能够预防因降糖治疗不足而引起的长期葡萄糖毒性和脂毒性的治疗策略的可用性可能有助于减轻糖尿病和相关代谢异常的血管并发症的临床和经济负担。

关键词: 糖尿病，血管并发症，动脉粥样硬化，糖尿病肾病，肌肽，活性羰基物质，晚期糖基化终产物，代谢记忆。

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