糖脂代谢病的发病机制:多重打击学说
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国家自然科学基金重点项目(81830113)——调肝启枢化浊法调控宿主-肠道菌群对话干预糖脂代谢紊乱的作用及机制研究


The Multiple-hit Pathogenesis of Glucolipid Metabolic Disorders
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    摘要:

    血糖异常、血脂异常、非酒精性脂肪肝、超重、高血压、动脉粥样硬化性心脑血管病等代谢性疾病发病率居高不下,是世界性难题。临床流行病学研究目前已证实,2型糖尿病、高脂血症等代谢性疾病常合并发生,但目前对导致上述代谢异常发生的分子机制尚未阐明,并制约了综合防控疗效优良的创新药物和诊疗手段的研发。郭姣教授率团队基于大样本临床流行病学、转化研究数据,提出“糖脂代谢病”创新理论,认为上述代谢异常以糖、脂代谢紊乱为特征,发病过程由遗传、环境、精神等多种因素参与,以神经-内分泌失调、胰岛素抵抗、氧化应激、炎性反应、肠道菌群失调为核心病理,以高血糖、血脂失调、非酒精性脂肪肝、超重、高血压及动脉粥样硬化等单一或合并出现为主要临床表现特点。本文综合神经-内分泌-免疫紊乱、胰岛素抵抗、氧化应激、炎性反应、肠道菌群失调等环节与糖脂代谢异常及其诱发多器官病变的病理机制的研究进展,提出糖脂代谢病发病机制的“多重打击学说”。该学说对于揭示多种代谢异常发生的核心、共性分子机制及从病证结合角度阐释中医证候的生物学本质具有重要意义。

    Abstract:

    The high prevalence and incidence of hyperglycemia,dyslipidemia,nonalcoholic fatty liver disease,obesity,hypertension,atherosclerosis and its related cardiovascular diseases has emerged as one of leading causes of morbidity and mortality worldwide.Epidemiological data well established that two or several above-mentioned metabolic disorders usually co-exist in obese subjects.However,the mechanisms underlying the co-existence of these metabolic disorders have not been well characterized currently,exerting negative effect on the development of new drugs and therapeutic approaches for these diseases.Based on the data from epidemiological and translational studies,Professor Jiao Guo and research team proposed a novel concept “Glucolipid Metabolic Disorders”(GLMD),which highlights the disorders in the metabolism of glucose and lipid as the key player in the pathogenesis of metabolic disorders.Genetic,environmental,and mental factors work together to contribute the development of GLMD.The dysfunction in neuroendocrine axis,insulin resistance,oxidative stress,metabolic inflammation,and alteration in gut microbiota represent the key mechanisms corresponding to the progression of these metabolic disorders.This article summarizes the recent findings in the relationship among these mechanisms and the development of GLDM and proposes the multiple-hit hypothesis for the pathogenesis of GLMD.This hypothesis is of significant importance for the clarification of the biological essence of Zheng in Traditional Chinese Medicine.

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华爽,吕明慧,刘倩颖,何兴祥,荣向路,叶得伟,郭姣.糖脂代谢病的发病机制:多重打击学说[J].世界中医药,2019,(03).

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  • 收稿日期:2019-02-01
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  • 在线发布日期: 2019-04-01
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