糖尿病合并代谢相关脂肪性肝病的肠道菌群特征研究

目的 探讨糖尿病合并代谢相关脂肪性肝病(MAFLD)的发生发展与脂肪代谢相关基因及肠道菌群之间的相关性,为糖尿病合并MAFLD的防治提供了的新思路。方法 21只C57BL/6雄性小鼠随机分为糖尿病组(6只)和糖尿病合并MAFLD组(15只),分别在糖尿病组小鼠和糖尿病合并MAFLD组小鼠给予高糖高脂饲料喂养35d和63d后,对两组小鼠血糖、血脂、肝功能、胰岛素、肝脏脂蛋白脂肪酶(LPl)和脂肪酸合成酶(Fasn)水平以及肠道菌群进行检测,并观察糖尿病合并MAFLD组小鼠肝脏HE染色及肠道紧密连接蛋白的变化情况。将2021年11月至2022年6月在沈阳市第六人民医院住院的15例糖尿病患者分为糖尿病组(7例)和糖尿病合并MAFLD组(8例),后者又分为肥胖型(BMI>30kg/m²)4例和非肥胖型(BMI8.5～22.9kg/m²)4例,对患者的粪便标本进行肠道菌群的宏基因检测。结果 与糖尿病组小鼠相比,糖尿病合并MAFLD组小鼠的血脂、肝功能及胰岛素水平降低,血糖、肝脏LPl和Fasn水平升高,高密度脂蛋白胆固醇、LPl和Fasn组间比较...     

肠道菌群对非酒精性脂肪性肝病铁代谢的影响

<正>非酒精性脂肪性肝病(NAFLD)是与胰岛素抵抗(IR)及遗传易感性密切相关的一组以肝脏脂质过度蓄积为主要病理表现的慢性代谢性肝脏疾病^[1]。其主要包括：单纯性脂肪肝、非酒精性脂肪性肝炎(NASH)、NASH相关性肝硬化。预计到2030年中国的NAFLD总人数将增加到3.145 8亿例,是全球NAFLD患病率增长最快的国家^[2]。然而,关于NAFLD的发病机制目前尚未完全阐明。“多重打击学说”是当前研究最多的NAFLD的发病机制,     

代谢相关性脂肪性肝病小鼠不同高脂饮食时期血糖水平和肠道菌群变化动态分析

目的 探讨在不同高脂饮食喂养时期代谢相关性脂肪性肝病(MAFLD)小鼠血糖水平和肠道菌群的动态变化.方法 采用高脂食物饲喂12只C57BL/6小鼠24周,分别在喂养0周、8周、16周和24周行葡萄糖耐量试验(GTT)和胰岛素耐受试验(ITT).采集小鼠粪便进行16sRNA检测,分析肠道细菌结构和肠道菌群多样性的变化.结...     

肠道菌群代谢产物在非酒精性脂肪性肝病发病中的作用机制研究进展

非酒精性脂肪性肝病（NAFLD）是一种代谢相关的慢性肝脏疾病,主要病因为肝脏内脂质堆积过多,可逐渐发展为肝纤维化、肝硬化甚至肝癌。肠道菌群是人体内微生物群的重要组成部分,可通过肠肝轴（GLA）参与NAFLD的发病过程,其分泌的代谢产物短链脂肪酸、胆汁酸、细菌成分、内源性乙醇及胆碱在NAFLD发病过程中均发挥重要作用。肠道菌群代谢产物与NAFLD的发病机制存在密切关联,深入了解其作用机制,或可为通过肠道微生态预防及治疗NAFLD提供理论依据。     

饮食干预对非酒精性脂肪性肝病肠道菌群的影响

非酒精性脂肪性肝病(NAFLD)的发生与遗传和环境密切相关,肠道菌群在其发生和发展中发挥了重要作用,调节肠道菌群已成为干预NAFLD的重要靶点之一.无论是饮食总量还是结构都会对肠道菌群产生直接且长期的影响.通过低脂饮食、增加饮食中不饱和脂肪酸或者增加难以吸收的多糖等方式调整饮食结构,可以有效调节肠道菌群并治疗NAFLD,但高蛋白饮食的作用还存在争议.     

肠道菌群与非酒精性脂肪性肝病

非酒精性脂肪性肝病（NAFLD）是一种常见慢性肝病,发病率呈逐年升高趋势,已逐渐引起人们的重视。1998年马歇尔正式提出了“肠-肝轴”的概念,肠道内环境与肝脏关系密切,越来越多的证据表明肠道菌群失调在NAFLD发病机制中起到了重要的作用。本文介绍了肠道菌群与NAFLD发病机制的关系。     

肠道菌群与脂肪性肝病研究新进展

目前,肠道菌群已成为一个当今研究的热点问题之一.脂肪性肝病是指由于各种原因引起的肝细胞内脂肪堆积过多的病变,引起肝的正常结构、生理及生化功能受损,最终出现临床症状的一类疾病总称,一般包括非酒精性脂肪性肝病和酒精性肝病两大类.肠道菌群和肠道通透性的变化可以通过肠-肝轴进一步影响脂肪性肝病的发展.同样,在脂肪性肝病的发生发...     

代谢相关脂肪性肝病肝外并发症研究进展与现状

代谢相关脂肪性肝病(metabolic associated fatty liver disease,MAFLD)是作为描述这种疾病的一个更合适的总括述语,新的定义将代谢功能障碍列为肝病的重要病因,论证了MAFLD的高异质性,加快了向新治疗的转化路径.MAFLD的肝外并发症其发生率和相关疾病,远远超过肝病本身,严重威脅着人类健康.鉴于当前人们对其严重性认识不足,且对肝外并发病的疾病范围、发病机制、诊断的研究还不完善,尤其当前对其缺乏有效的药物治疗,有鉴于此本文就MAFLD肝外并发症研究现状与进展作一介绍与述评,与广大读者共享.     

Macrophages in metabolic associated fatty liver disease

Metabolic associated fatty liver disease(MAFLD), formerly named non-alcoholic fatty liver disease is the most common liver disorder in many countries. The inflammatory subtype termed steatohepatitis is a driver of disease progression to cirrhosis, hepatocellular carcinoma, liver transplantation, and death, but also to extrahepatic complications including cardiovascular disease, diabetes and chronic kidney disease. The plasticity of macrophages in response to various environmental cues and the fact that they can orchestrate cross talk between different cellular players during disease development and progression render them an ideal target for drug development. This report reviews recent advances in our understanding of macrophage biology during the entire spectrum of MAFLD including steatosis, inflammation, fibrosis, and hepatocellular carcinoma, as well as for the extra-hepatic manifestations of MAFLD. We discuss the underlying molecular mechanisms of macrophage activation and polarization as well as cross talk with other cell types such as hepatocytes, hepatic stellate cells, and adipose tissue. We conclude with a discussion on the potential translational implications and challenges for macrophage based therapeutics for MAFLD.     

代谢相关性脂肪性肝病患者发生明显肝纤维化的危险因素研究

目的分析经肝活检确诊的代谢相关性脂肪性肝病(metabolic associated fatty liver disease, MAFLD)患者发生明显肝纤维化的危险因素。方法回顾性分析193例经肝活检确诊的MAFLD患者发生明显肝纤维化的危险因素。结果与MAFLD伴无/轻微肝纤维化(F0~1)患者比较,MAFLD伴明显肝纤维化(F2~4)患者中女性比例更高、年龄更大、肥胖更多见、伴高血压病者更多(P均<0.05);与MAFLD伴无/轻微肝纤维化(F0~1)患者比较,MAFLD伴明显肝纤维化(F2~4)患者外周血中血红蛋白水平及血小板计数更低(P<0.05),血清中白蛋白及尿酸水平更低(P<0.05),而TBA及空腹血糖水平更高(P<0.05)。单因素回归分析发现,女性(OR=2.277, 95%CI:1.181~4.390)、高血压病(OR=3.305, 95%CI:1.606~6.801)、BMI(OR=1.083, 95%CI:1.006~1.167)、年龄(OR=1.030,95%CI:1.006~1.055)、血红蛋白(OR=0.978,95%CI:0.958~0.997)及血小板计数(OR=0.998,95%CI:0.989~1.000)是MAFLD患者发生明显肝纤维化的危险因素,而多因素回归分析发现,高血压病(OR=2.662,95%CI:1.092~6.489)、BMI(OR=1.163,95%CI:1.062~1.275)及血小板计数(OR=0.993,95%CI:0.987~0.999)是MAFLD患者发生明显肝纤维化的独立危险因素。结论高血压、BMI及血小板计数是肝活检确诊的MAFLD患者发生明显肝纤维化的独立危险因素。     

代谢相关性脂肪性肝病无创诊断方法研究进展

据估计,全球约有25%的成年人患有代谢相关性脂肪性肝病(metabolic associated fatty liver disease,MAFLD),且发病率逐年上升。肝脏活检仍是诊断MAFLD的金标准。近年来,无创诊断方法发展比较迅速。本文针对MAFLD的无创诊断研究进展进行了较为系统的综述。     

Comments on validation of conventional non-invasive fibrosis scoring systems in patients with metabolic associated fatty liver disease

To evaluate and predict liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), several non-invasive scoring systems were built and widely used in the progress of diagnosis and treatment, which showed great diagnostic efficiency, such as aspartate aminotransferase to platelet ratio index, fibrosis-4 index, body mass index, aspartate aminotransferase to alanine aminotransferase ratio, diabetes score and NAFLD fibrosis score. Since the new concept of metabolic associated fatty liver disease (MAFLD) was proposed, the clinical application value of the non-invasive scoring systems mentioned above has not been assessed in MAFLD. The evaluation of the diagnostic performance of these non-invasive scoring systems will provide references for clinicians in the diagnosis of MAFLD.     

Metabolic associated fatty liver disease: Addressing a new era in liver transplantation

Metabolic associated fatty liver disease (MAFLD), previously termed non-alcoholic fatty liver disease, is the leading global cause of liver disease and is fast becoming the most common indication for liver transplantation. The recent change in nomenclature to MAFLD refocuses the conceptualisation of this disease entity to its metabolic underpinnings and may help to spur a paradigm shift in the approach to its management, including in the setting of liver transplantation. Patients with MAFLD present significant challenges in the pre-, peri- and post-transplant settings, largely due to the presence of medical comorbidities that include obesity, metabolic syndrome and cardiovascular risk factors. As the community prevalence of MAFLD increases concurrently with the obesity epidemic, donor liver steatosis is also a current and future concern. This review outlines current epidemiology, nomenclature, management issues and outcomes of liver transplantation in patients with MAFLD.     

胡桃苷对非酒精性脂肪性肝小鼠中肝脂质代谢紊乱、肝损伤以及小肠完整性的改善作用

背景现有研究对胡桃苷在非酒精性脂肪性肝病(nonalcoholicfattyliverdisease,NAFLD)中的治疗作用尚未得到充分关注.目的本研究通过高脂饮食(high fatty diet, HFD)小鼠模型评估了胡桃苷在NAFLD中的治疗效果.方法C57B L/6小鼠分为标准饮食组、H F D组、胡桃苷低、中和高剂量治疗组.给药方案结束后,采集小鼠血样和组织(肝和小肠)进行生化及组织学测定.结果胡桃苷抑制了HFD诱导的肝组织形态学改变和肝脂质沉积,并降低了血清中谷草转氨酶、谷丙转氨酶和胆固醇含量以及葡萄糖、血清胰岛素水平和胰岛素抵抗稳态模型值.胡桃苷显著改善了HFD引起的代谢损伤,增加了肝脏过氧化物酶体增殖体激活受体及其下游调节基因成纤维细胞生长因子21的m RNA水平,并且提高了乙酰辅酶A羧化酶的磷酸化水平和肉碱-棕榈酰基转移酶的m RNA水平.此外,胡桃苷还减少了肝脏炎症,恢复了肠道屏障的完整性和功能(FITC-dextran通透性下降和小肠组织紧密连接蛋白1表达增加).结论胡桃苷可恢复NAFLD引起的脂肪变性、减少肝脏炎症、恢复葡萄糖稳态和改善肠道完整性.