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据估计,2017 年全球有 4.51 亿(18~99 岁)糖尿病(DM)患者,预计到 2045 年,这一数字将增至 6.93 亿[1]。糖尿病肾病(DKD)是DM的一种严重并发症,是世界范围内终末期肾病(ESRD)的主要病因[2, 3]。DKD的发生率与DM的发病率和病死率增加密切相关[4]。在美国,开始接受ESRD治疗的DM患者数量从2000年的4万多人显著增加到2014年的5万多人[5]。在我国,DKD的发病率在过去10年中显著增加,2013年的一项调查结果显示,中国DKD患者数量估计达到2 430万[6]。当前,DM患病率持续上升,如果DKD的临床预防策略没有改善,预计DKD的患病率也会随之增加[7, 8]。然而目前除了控制血糖、血压等手段外,临床上尚无其他有效预防DKD的方案。DKD的发病机制复杂,其分子机制还没有得到全面阐明。近年来,越来越多的研究发现,肠道菌群在DKD的发生发展中发挥了重要作用,本文围绕DKD的肠道菌群参与情况,综述其研究进展。
肠道菌群是一个由微生物菌落组成的复杂生态系统,包括至少1 000个不同物种的数万亿细菌,另外还有其他共生生物,如古细菌、病毒、真菌和原生生物。肠道菌群失调的主要特征是细菌和真菌的多样性和丰度下降[9]。近年来,人们对肠道菌群与宿主相互作用产生极大兴趣,众多证据表明,肠道菌群在人类健康和疾病中发挥重要作用,菌群失调已被证明与动脉粥样硬化、高血压、心力衰竭、慢性肾病(CKD)、肥胖和2型糖尿病(T2DM)等疾病有关[10]。肠道菌群有能力产生一系列代谢产物,包括短链脂肪酸(SCFAs)、N-氧化三甲胺(TMAO)、胆汁酸(BA)、蛋白质结合的尿毒症毒素(PBUT)、支链氨基酸(BCAAs)和一些其他未知代谢产物。肠道微生物产生的代谢产物被认为是微生物与宿主之间交流的媒介,对人体的生物活性和代谢有重要影响[11]。近年来,许多研究调查了DM、肥胖和代谢综合征等代谢性疾病患者肠道微生物群的多样性和功能的变化。有研究发现,这些患者的肠道微生物群落发生了显著变化,并导致肠道微生物群失调和肠漏综合征,肠道屏障功能障碍,肠道通透性增加[12]。多种肠道微生物群代谢产物被释放到血液中,如SCFAs、TMAO、脂多糖(LPS)和尿毒症毒素,再通过多种信号通路进一步导致疾病表型的变化[13, 14]。
Research progress on the mechanism of gut microbiota participating in diabetes nephropathy
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摘要: 随着糖尿病患病率升高,糖尿病肾病的预防和治疗已成为世界性难题。糖尿病肾病发生发展的分子机制目前尚不明确,但近年来诸多研究表明,肠道菌群在糖尿病肾病的进展中发挥重要作用。综述了肠道菌群参与糖尿病肾病的机制研究进展。Abstract: With the increasing prevalence of diabetes, the prevention and treatment of diabetes nephropathy have become a worldwide problem. The molecular mechanism of the occurrence and development of diabetes nephropathy is still unclear, but many studies in recent years have shown that gut microbiota plays an important role in the progress on diabetes nephropathy. The research progress on the mechanism of gut microbiota participating in diabetes nephropathy was reviewed in this article.
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Key words:
- diabetes /
- diabetes nephropathy /
- intestinal flora /
- intestinal permeability
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