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胆汁酸和法尼醇 X 受体:治疗糖尿病心肌病的新靶点。

Bile Acids and Farnesoid X Receptor: Novel Target for the Treatment of Diabetic Cardiomyopathy.

机构信息

Shandong University of Traditional Chinese Medicine, Jinan, 250000, China.

Department of Clinical Pharmacology and Toxicology, University Hospital of Zurich, Zurich, 8032, Switzerland.

出版信息

Curr Protein Pept Sci. 2019;20(10):976-983. doi: 10.2174/1389203720666190726152847.

Abstract

Diabetes mellitus (DM) has become an increasingly common disease with high disability and mortality rates. Diabetes complications are the main cause of diabetes death and about 50% of diabetic patients died from heart disease in developed countries reported by World Health Organization. Diabetic cardiomyopathy (DCM) has been considered as a high incidence and serious complication of DM and plays a key role in the incidence and development of diabetes related heart failure. Metabolism dysregulation is regarded as an important and earlier factor occurred in the pathogenesis of DCM. Insulin resistance, oxidative stress, inflammation and mitochondrial dysfunction also contribute to the development of DCM. Farnesoid X Receptor (FXR) is a member of nuclear receptor superfamily, and plays a critical role in regulating lipid and glucose metabolism, oxidative stress and inflammation. FXR is activated by primary bile acids (BAs) such as chenodeoxycholic acid, cholic acid and synthetic agonists such as obeticholic acid. BAs are the main active ingredients of many natural products and traditional medicines, especially bile or gallstones in animals, such as calculus bovis. Due to the regulatory effect of FXR on glucose and lipid metabolism, oxidative stress and inflammation, the treatment of BAs and FXR agonists for metabolic syndrome and DCM have gained more attention. This review will focus on the pathogenesis of diabetic cardiomyopathy and the regulatory effect of BAs and FXR on DCM.

摘要

糖尿病(DM)已成为一种越来越常见的疾病,其具有高致残率和高死亡率。糖尿病并发症是糖尿病死亡的主要原因,世界卫生组织报告称,在发达国家约有 50%的糖尿病患者死于心脏病。糖尿病心肌病(DCM)已被认为是 DM 的一种高发病率和严重并发症,在糖尿病相关心力衰竭的发生和发展中起着关键作用。代谢失调被认为是 DCM 发病机制中一个重要且较早发生的因素。胰岛素抵抗、氧化应激、炎症和线粒体功能障碍也促成了 DCM 的发展。法尼醇 X 受体(FXR)是核受体超家族的成员,在调节脂质和葡萄糖代谢、氧化应激和炎症方面发挥着关键作用。FXR 被初级胆汁酸(BAs)如鹅脱氧胆酸、胆酸和合成激动剂如奥贝胆酸激活。BAs 是许多天然产物和传统药物的主要活性成分,特别是动物的胆汁或胆结石,如牛黄。由于 FXR 对葡萄糖和脂质代谢、氧化应激和炎症的调节作用,BAs 和 FXR 激动剂治疗代谢综合征和 DCM 引起了更多关注。这篇综述将重点介绍糖尿病心肌病的发病机制以及 BAs 和 FXR 对 DCM 的调节作用。

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