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晚期糖基化终产物与慢性肾脏病患者肌肉减少症和衰弱的关系。

Association of advanced glycation end products with sarcopenia and frailty in chronic kidney disease.

机构信息

Department of Nephrology, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.

Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.

出版信息

Sci Rep. 2020 Oct 19;10(1):17647. doi: 10.1038/s41598-020-74673-x.

Abstract

Prevalence of sarcopenia is high in patients with chronic kidney disease (CKD), especially in those with dialysis. Various pathological conditions related to CKD, such as chronic inflammation, insulin resistance, and endothelial dysfunction, are thought to be associated with the development and progression of sarcopenia. Advanced glycation end products (AGE), one of the representative uremic toxins, have been shown to contribute to various CKD-associated complications. This study investigated the role of AGE in frailty and sarcopenia in patients and animals with CKD, respectively. In patients undergoing dialysis, serum AGE levels were significantly increased according to the frailty status and inversely associated with physical performance and activity. AGE accumulated in the gastrocnemius muscle of 5/6 nephrectomy mice in association with morphological abnormalities, capillary rarefaction, and mitochondrial dysfunction, all of which were completely inhibited by DNA-aptamer raised against AGE. Our present findings may suggest the pathological role of AGE in sarcopenia and frailty in CKD.

摘要

肌肉减少症在慢性肾脏病(CKD)患者中较为常见,尤其是透析患者。与 CKD 相关的各种病理状态,如慢性炎症、胰岛素抵抗和内皮功能障碍,被认为与肌肉减少症的发生和发展有关。晚期糖基化终产物(AGE)是一种代表性的尿毒症毒素,它被认为与多种 CKD 相关的并发症有关。本研究分别探讨了 AGE 在 CKD 患者和动物的虚弱和肌肉减少症中的作用。在接受透析的患者中,根据虚弱状况,血清 AGE 水平显著升高,并且与身体机能和活动呈负相关。AGE 在 5/6 肾切除小鼠的比目鱼肌中堆积,与形态异常、毛细血管稀疏和线粒体功能障碍有关,这些都可以被针对 AGE 的 DNA 适体完全抑制。我们目前的研究结果可能提示 AGE 在 CKD 肌肉减少症和虚弱中的病理作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91b2/7573579/9c441ad10771/41598_2020_74673_Fig1_HTML.jpg

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