微小RNA在脂肪性肝病研究中的新进展

微小RNA(microRNA,miRNA)是一类长度约为22个核苷酸的内源性非编码小分子RNA,它通过对目标mRNA的剪切和翻译抑制,在转录后水平对动植物起到重要的调控作用。在细胞增殖、凋亡和分化,肿瘤形成,免疫反应,个体发育等病理生理活动中具有至关重要的作用。近年来研究表明,部分miRNA在NAFLD中有不同程度的差异性表达,此文就miRNA的生物学特征及与NAFLD的关系研究进行概述。     

非酒精性脂肪性肝病中microRNA调控细胞凋亡的机制

非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)是西方发达国家常见的肝脏疾病,其患病率在发展中国家也持续增高.NAFLD是一类肝脏疾病的总称,其中单纯性脂肪肝属良性病变,但非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)可进一步发展为肝纤维化、肝硬化,最终导致肝癌,但NAFLD的发病机制并不完全清楚.微小RNA(microRNA,miRNA)作为一类在转录后水平调控机体生长发育、细胞代谢、增殖、分化、凋亡及肿瘤形成等生理、病理过程的非编码RNA,也参与了NAFLD的发病.miRNA种类繁多,广泛参与NAFLD中胰岛素抵抗、脂代谢紊乱、内质网损伤和细胞凋亡等过程.本文主要就miRNA在NAFLD细胞凋亡中的作用作一综述.     

长链非编码RNA的竞争性内源RNA调控模式在动脉粥样硬化中的研究进展

动脉粥样硬化是一种缓慢进行性的血管炎症性病变。越来越多的研究表明长链非编码RNA(lncRNA)作为竞争性内源RNA(ceRNA)与微小RNA(miRNA)结合,通过ceRNA网络调控靶基因信使RNA(mRNA)分子的表达水平和功能,在动脉粥样硬化的病理生理过程中发挥重要作用。lncRNA、miRNA和mRNA之间的互作调控机制复杂。本文综述了lncRNA-miRNA-mRNA调控网络在动脉粥样硬化发病机制中的调控关系,阐述该调控网络在内皮细胞功能障碍、血管平滑肌细胞表型转化、巨噬细胞激活以及脂质代谢异常等病变中的重要作用,为动脉粥样硬化临床诊疗提供新思路。     

miRNA:急性心肌梗死治疗新战略标靶

微小RNA(MircroRNA,miRNA)是由21~23个核苷酸组成的内源性非编码单股小RNA,通过与目标信使RNA(messenger RNA,mRNA)的3′-非翻译端(3′-UTR)整合使其翻译减少或降解,从而调控基因的表达[1],进而调控众多的生理和病理生理过程,是基因表达的重要调节器.最先确认的miRNA是控制线虫发育关键步骤的lin-4和let-7,随后的研究在包括人类、果蝇、植物等多种生物物种中通过分子克隆和生物信息学鉴别出数百个miRNA[2].     

微小RNA与糖尿病及其并发症关系的研究进展

微小RNA(miRNA)是一种新型的非编码RNA,能在转录后水平调控基因的表达,且参与人体多种生理和病理过程的调控。近年来,研究表明,miRNA异常表达在糖尿病及其并发症的发生发展中起重要作用。本文就miRNA与糖尿病及其并发症的关系作简要综述。     

miRNA与消化系统肿瘤的关系

微小RNA(miRNA)是一类广泛存在于多种生物体内的长度约22个核苷酸的非编码小分子RNA,能够在后转录水平负调控基因表达.miRNA在细胞产生、增殖及凋亡过程中发挥特有的负性调控作用,与人类许多疾病(包括肿瘤)的发生发展密切相关.近来的研究证实miRNA在人类肿瘤中可能是潜在的癌基因或抑癌基因,本文就miRNA与消化系统肿瘤的关系的研究进展作一综述.     

长链非编码RNA作为ceRNA在结直肠癌中的作用

结直肠癌(colorectal cancer,CRC)是全球第三大恶性肿瘤,恶性程度高,具有很高的转移和复发率。长链非编码RNA(lncRNA)在CRC发生发展过程中发挥重要作用。最近的研究表明,lncRNA可通过与微小RNA(miRNA)的反应元件(MRE)结合,充当竞争性内源RNA(ceRNA),从而间接调控miRNA导致的基因沉默。lncRNA/miRNA/mRNA相互作用形成的ceRNA网络广泛参与CRC的生物学过程,包括肝转移、上皮-间质转化(EMT)、炎症形成和放化疗抵抗等。本文结合国内外最新相关研究,就lncRNA作为ceRNA在CRC中的调控作用,以及治疗和预后方面的临床应用价值作一概述。     

微小RNA与心律失常

目前发现多种临床心律失常综合征与微小RNA(miRNA)有关。miRNA在基因转录后调节中扮演重要角色。它影响离子通道基因的表达,同时也影响非离子通道基因表达,从而参与调节心脏节律。不同病理状态(如心肌梗死、心肌肥厚等)下,miRNA表达的异常,导致其所调控基因的表达改变,是心律失常发生的重要机制。对miRNA的研究,有助于阐明心律失常的发生机制,开拓心律失常治疗的新途径。     

microRNA在心力衰竭病理变化过程中的调节意义

微小RNA(microRNA,miRNA)是一组高度保守的内源性非编码小RNA,其通过沉默或降解信使核糖核酸而调节基因表达和蛋白翻译,约1/3的人类基因受到miRNA的调节。在心血管领域,它参与心脏如心肌纤维化、心肌肥厚、心肌凋亡、心力衰竭等病理改变的调节过程。明确miRNA在心血管疾病中的作用对其应用研究的开展有着重要意义。     

长链非编码RNA在非酒精性脂肪性肝病发生发展中的调控作用

非酒精性脂肪性肝病(NAFLD)是以肝细胞发生脂肪变性、脂质代谢紊乱以及异常沉积为特征的病理变化,是最常见的肝脏疾病。长链非编码RNA(lncRNA)在NAFLD发生发展中的作用已成为当前的研究热点。总结了NAFLD中重要的lncRNA,其主要参与调节脂质代谢、糖代谢、炎性变化等信号通路;阐述了其促进NAFLD发生以及向肝炎、肝纤维化转变的作用机制。未来多基因组学和蛋白组学的深入研究将促进NAFLD精确的靶向治疗。     

MicroRNAs as controlled systems and controllers in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a multi-faceted condition including simple steatosis alone or associated with inflammation and ballooning (non-alcoholic steatohepatitis) and eventually fibrosis. The NAFLD incidence has increased over the last twenty years becoming the most frequent chronic liver disease in industrialized countries. Obesity, visceral adiposity, insulin resistance, and many other disorders that characterize metabolic syndrome are the major predisposing risk factors for NAFLD. Furthermore, different factors, including genetic background, epigenetic mechanisms and environmental factors, such as diet and physical exercise, contribute to NAFLD development and progression. Several lines of evidence demonstrate that specific microRNAs expression profiles are strongly associated with several pathological conditions including NAFLD. In NAFLD, microRNA deregulation in response to intrinsic genetic or epigenetic factors or environmental factors contributes to metabolic dysfunction. In this review we focused on microRNAs role both as controlled and controllers molecules in NAFLD development and/or their eventual value as non-invasive biomarkers of disease.     

非酒精性脂肪性肝病与肠道菌群的关系

非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)是一种多病因导致的临床病理综合征,已成为最常见的慢性肝病之一,目前NAFLD完整的生理机制尚不完全清楚,近年来提出肠道菌群通过调控能量代谢、增加内源性乙醇、调节胆汁酸及胆碱代谢,破坏免疫平衡引发机体低度炎症等途径促进NAFLD的发生、发展,本文就肠道菌群与NAFLD的相关机制做一概述。     

Roles of microRNAs in immunopathogenesis of non-alcoholic fatty liver disease revealed by integrated analysis of microRNA and mRNA expression profiles

BACKGROUND:The integrative analysis of microRNA and mRNA expression profiles can elucidate microRNA-targeted gene function.We used this technique to elucidate insights into the immunological pathology of non-alcoholic fatty liver disease (NAFLD).METHODS:We analyzed differentially expressed microRNA and mRNA expression profiles of CD4+ T lymphocytes from the liver and mesenteric lymph nodes (MLNs) of mice with NAFLD using microarrays and RNA sequencing.Normal mice were used as controls.The target genes of microRNAs were predicted by TargetScan.Integrative analysis showed that the mRNAs were overlapped with microRNAs.Furthermore,the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the key genes and pathways.Then,16 microRNAs and 10 mRNAs were validated by qRT-PCR.RESULTS:Microarray analysis suggested that 170 microRNAs were significantly de-regulated in CD4+ T lymphocytes from the liver between the two groups.Eighty mRNAs corresponded with microRNA targeted genes.KEGG analysis indicated that the MAPK pathway was consistently augmented in the liver of NAFLD mice.miR-23b,let-7e,miR-128 and miR-130b possibly played significant parts in the MAPK pathways.Furthermore,between the two groups,237 microRNAs were significantly deregulated in CD4+ T lymphocytes from MLNs.38 mRNAs coincided with microRNA target genes.The metabolic pathway was consistently enriched in the MLNs of NAFLD mice.miR206-3p,miR-181a-Sp,miR-29c-3p and miR-30d-5p likely play important roles in the regulation of metabolic pathways.CONCLUSION:The results of this study presented a new perspective on the application of integrative analysis to identify complex regulation means involved in the immunological pathogenesis of NAFLD.     

非酒精性脂肪性肝病分级分期管理研究进展

非酒精性脂肪性肝病（NAFLD）是代谢综合征在肝脏的病理学表现。由于饮食结构的改变,NAFLD发病率呈现上升趋势,且NAFLD与肝病进展、糖尿病和心血管疾病死亡密切相关。因此,寻求NAFLD患者综合管理方法迫在眉睫。本文综述了NAFLD分级、分期、治疗和随访评估的研究进展,以期指导临床诊断、治疗和管理。     

非酒精性脂肪性肝病的病理特点分析

目的 总结10年来福建省漳州地区肝穿刺活检标本中非酒精性脂肪性肝病(NAFLD)的发病率及病理特征.方法 收集65例NAFLD患者的相关资料,肝组织标本常规行苏木精-伊红(HE)、Masson及网状纤维染色,观察其病理特点,并进行分级.结果 在所有3 000例行肝活检的病例中,出现肝细胞脂肪变的病例约占12.7%,而NAFLD的发生率约6.1%.肝组织病理学特征主要为肝细胞大泡性或以大泡为主的脂肪变性,邻近肝细胞不同程度肿胀乃至气球样变,病变越重,肝细胞气球样变越显著,典型Mallory小体未见;纤维化主要位于窦周及中央静脉管壁,脂肪性肝硬化时脂变的肝细胞及小叶内炎细胞均减少.结论 NAFLD是近年来较常见的慢性肝病,肝活检组织学评价是确诊的金标准.     

The clinical aspects of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) has been increasingly recognized as the most common pathological conditions affecting the liver. In concert with the increase in Body Mass Index in developed countries that has occurred during the last decades, more and more individuals referred for evaluation of abnormal liver tests are found to have NAFLD. In most cases, the increase in fat within the liver is not associated with impaired liver structure or function in the long-term. However, liver steatosis should be considered to be a marker of the metabolic syndrome. A minority of patients with NAFLD develop liver cirrhosis but NAFLD is probably the most common underlying cause of cryptogenic cirrhosis. Patients with NAFLD have an increased cardiovascular mortality as well as increase in liver related complications compared with matched controls. The diagnostic evaluation of a patient with suspected NAFLD depends heavily on the setting. In whom and when a liver biopsy is indicated is controversial. An adequate history is of major importance and when alcohol is suspected to be a contributing factor to the liver steatosis, several biochemical and clinical parameters may differentiate alcoholic fatty liver and NAFLD. Unfortunately, no histological gold standard is available for non-alcoholic steatohepatitis (NASH) and there is still a significant diversity among pathologist concerning the minimal requirements for the term NASH. Management of patients with NAFLD should be aimed at fighting the metabolic risk factors such as visceral obesity, hyperglycemia, type II diabetes mellitus (DM) and hypertriglyceridemia. DM has been shown to be a predictor of worsening of fibrosis. Successful lifestyle modification with increased exercise and decreased food intake is able to remove the accumulation of liver fat and can reverse insulin resistance. Unfortunately, there are no well-controlled, randomized trials of weight control as therapy for NAFLD. Some pharmacological pilot trials have been undertaken in NAFLD, but no proved treatment for all patients with NAFLD and/or NASH is available at the current time.     

Noncoding RNAs as additional mediators of epigenetic regulation in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common cause of chronic liver disorder worldwide. It represents a spectrum that includes a continuum of different clinical entities ranging from simple steatosis to nonalcoholic steatohepatitis, which can evolve to cirrhosis and in some cases to hepatocellular carcinoma, ultimately leading to liver failure. The pathogenesis of NAFLD and the mechanisms underlying its progression to more pathological stages are not completely understood. Besides genetic factors, evidence indicates that epigenetic mechanisms occurring in response to environmental stimuli also contribute to the disease risk. Noncoding RNAs (ncRNAs), including microRNAs, long noncoding RNAs, and circular RNAs, are one of the epigenetic factors that play key regulatory roles in the development of NAFLD. As the field of ncRNAs is rapidly evolving, the present review aims to explore the current state of knowledge on the roles of these RNA species in the pathogenesis of NAFLD, highlight relevant mechanisms by which some ncRNAs can modulate regulatory networks implicated in NAFLD, and discuss key challenges and future directions facing current research in the hopes of developing ncRNAs as next-generation non-invasive diagnostics and therapies in NAFLD and subsequent progression to hepatocellular carcinoma.     

非酒精性脂肪性肝病的无创性诊断方法

肝活组织检查（LB）是评估非酒精性脂肪性肝病（NAFLD）肝脏病理损伤程度的＂金标准＂,但因其有创性,未能广泛应用于临床。近年来非酒精性脂肪性肝炎（NASH）和进展期肝纤维化无创诊断方法研究进展较快,从临床及生物化学指标、生物标志物、影像学技术方面简述了诊断价值较高的部分无创诊断方法。目前认为NAFLD无创诊断方法尚不能取代LB,但联合应用血清细胞角蛋白18片段和NAFLD纤维化评分、瞬时弹性成像可初步诊断NASH及伴或不伴进展期肝纤维化,并进一步确定LB的使用。     

我国非酒精性脂肪性肝病的诊疗进展

随着生活条件的不断提高及饮食结构的改变，非酒精性肝病(NAFLD)发病率不断升高，成为一个全球化的问题，在我国也引起了广泛的关注。NAFLD具有早期发病隐匿的特点，目前临床常规诊断需要影像学检查、实验室检查等无创检查手段，以及必要时的病理有创检查，其中病理是诊断NAFLD及病情进展的金标准。NAFLD治疗的首要目标是减肥和改善胰岛素抵抗，预防及治疗2型糖尿病(T2DM)、代谢综合征(MS)及相关的并发症，进而减轻疾病负担、改善患者生活质量并延长寿命，次要目标为减少肝脂肪沉积。改变生活方式是目前推荐的最有效的NAFLD改善方法。肥胖患者减肥是一种必要治疗措施，严重的NAFLD患者可以进行肝移植。     

非酒精性脂肪性肝病合并2型糖尿病患者肝组织病理学变化研究

目的 研究非酒精性脂肪性肝病（NAFLD）合并2型糖尿病（T2DM）患者肝脏组织病理学变化。方法 分析240例行肝活检术的NAFLD患者临床资料,比较NAFLD合并T2DM与未合并T2DM患者肝组织病理学表现和评分的差异。结果 在240例NAFLD患者中,合并2型糖尿病者80例（33.3%）,未合并T2DM 者160例（66.7%）;在NAFLD合并T2DM患者中非酒精性脂肪性肝炎（NASH）60例、肝纤维化20例,未合并T2DM患者中分别为68例和92例;在NAFLD合并T2DM患者中检出肝纤维化评分≥2者30例（37.5%）、肝细胞气球样变评分≥2者23例（28.8%）和马洛里小体22例（27.5%）,均显著高于未合并T2DM患者的【20例（12.5%）、22例（13.8%）和30例（18.8%）,P<0.05】;T2DM为发生NASH（OR=3.27,95%CI：1.42~7.55）和肝纤维化（OR=3.35,95%CI：1.55~7.63）的独立危险因素。结论 合并T2DM的NAFLD患者肝组织病理学损伤更趋严重,应注意防治。