ISSN 1006-298X      CN 32-1425/R

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肾脏病与透析肾移植杂志 ›› 2024, Vol. 33 ›› Issue (5): 474-479.DOI: 10.3969/j.issn.1006-298X.2024.05.014

• 肾脏病临床 • 上一篇    下一篇

靶向氧化三甲胺治疗慢性肾脏病的研究进展

  

  • 出版日期:2024-10-28 发布日期:2024-11-01

Advances in study on targeting trimethylamin N-oxide therapy for chronic kidney disease

  • Online:2024-10-28 Published:2024-11-01

摘要: 饮食来源胆碱经肠道微生物代谢后产生氧化三甲胺(TMAO),是心血管疾病、慢性肾脏病(CKD)、2型糖尿病等疾病进展的独立危险因素。TMAO在人体内主要经肾小球滤过和肾小管分泌排出,肾功能下降可致循环中TMAO浓度升高,诱导动脉粥样硬化,增加卒中风险,促进炎症反应和氧化应激,导致心肌与肾间质纤维化。钠-葡萄糖协同转运蛋白2抑制剂、肠促胰素类药物可改变循环TMAO浓度,此作用对原发病疗效的影响程度尚无定论。除调整饮食结构外,益生菌或益生元、三甲胺(TMA)抑制剂、黄素单加氧酶3(FMO3)抑制剂等靶向TMAO治疗药物可不同程度影响肠道TMAO生成,但对宿主全身及CKD疾病进程的确切影响仍需深入研究。本文总结了靶向TMAO治疗药物的研究进展,包括使用益生菌或益生元调节肠道菌群组成,降低代谢产生TMA水平,以及靶向抑制TMA产生菌生成TMAO等,为此类药物治疗CKD提供理论依据。


关键词: 慢性肾脏病, 氧化三甲胺, 治疗

Abstract: Diet-based choline is metabolized by gut microbes to produce trimethylamine oxide (TMAO), which is an independent risk factor for the progression of major diseases such as cardiovascular disease, chronic kidney disease (CKD), and type 2 diabetes. TMAO is excreted in the human body mainly by glomerular filtration and renal tubule secretion. Decreased renal function can lead to increased circulating TMAO concentration, induce atherosclerosis, increase the risk of stroke, promote inflammatory response and oxidative stress, and lead to myocardial and renal interstitial fibrosis. Sodium-glucose transporter 2 inhibitors and incretin can change the circulating TMAO concentration, and the effect on the primary disease remains to be determined. In addition to adjusting diet, targeted TMAO therapeutics such as probiotics or prebiotics, trimethylamine (TMA) inhibitors, and flavin monooxygenase 3 (FMO3) inhibitors can affect intestinal TMAO production to varying degrees, but the exact impact on body of the host and the course of CKD still needs further study. This review summaries the researching development progress of targeting TMAO drugs,such as regulating the composition of the gut microbiota and reduce the metabolic production of TMA levels by probiotics or prebiotics, inhibiting TMA producing bacteria from producing TMAO by TMA inhibitors, to provide theoretical basis for their use as new treatment strategies of CKD.


Key words: chronic kidney disease, trimethylamin N-oxide, treatment