全脑缺血/再灌注大鼠海马PPARα表达变化

目的观察全脑缺血/再灌注损伤大鼠海马组织中PPARα mRNA和蛋白表达的动态变化.方法采用夹闭两侧颈总动脉,颈静脉抽血再回输建立大鼠全脑缺血/再灌注模型(I/R).RT-PCR和Western Blot分别检测PPARα mRNA和蛋白在缺血再灌注不同时间的表达.结果大鼠海马PPARα mRNA表达在缺血/再灌注30 min后升高,24 h时达峰,而后降低,再灌注30 d仍略高于正常水平.PPARα蛋白表达变化与PPARα mRNA表达相似.结论全脑缺血/再灌注损伤可诱导PPARα mRNA及蛋白表达,升高时限为30 d.     

大鼠肢体缺血预处理对肝缺血/再灌注损伤的保护作用

目的：研究肢体缺血预处理对大鼠肝缺血/再灌注损伤是否具有保护作用。方法：雄性SD大鼠32只,随机分为对照组（S组）;缺血/再灌注组（I/R组）;经典缺血预处理组（IPC组）;肢体缺血预处理组（远端缺血预处理组,RPC组）。S组仅行开腹,不作其他处理;IPC组以肝缺血5min作预处理;RPC组以双后肢缺血5min,反复3次作预处理,2个预处理组及I/R组均行肝缺血1h再灌注3h。取血用于血清谷丙转氨酶（ALT）与血清谷草转氨酶（AST）检测。切取肝组织用于测定湿干比（W/D）、中性粒细胞（PMN）计数及观察显微、超微结构的变化。结果：与I/R组比较,IPC组,RPC组ALT,AST,W/D值,及PMN计数均明显降低（P〈0.01）,肝脏的显微及超微结构损伤减轻。结论：肢体缺血预处理对大鼠肝脏I/R损伤有明显的保护作用,强度与经典缺血预处理相当,其机制可能与抑制肝脏炎症反应、减轻肝脏水肿、改善肝组织微循环有关。     

有氧运动对非酒精性脂肪肝大鼠肝细胞PPAR琢mRNA 表达的影响*

目的：研究有氧运动对非酒精性脂肪肝大鼠肝细胞PPARα表达的影响,探讨运动对非酒精性脂肪肝的保护防治作用.方法：36只雄性SD大鼠随机分为对照组,高脂组和高脂运动组.后两组喂食普通饲料的同时在实验前三周给予脂肪乳剂灌胃,以诱发脂肪肝.七周有氧运动后测大鼠体重、肝湿重、测血浆TC、TG、ALT、SOD及MDA水平;采用荧光定量PCR法测肝细胞PPARα mRNA的表达水平.结果：1）与对照组相比,高脂组TC、TG显著升高（P＜0.05,P＜0.01）,高脂运动组均无显著性差异.高脂组TC、TG显著高于高脂运动组（P＜0.01,P＜0.01）.2）高脂组PPARα mRNA表达显著低于对照组（P＜0.05）和高脂运动组（P＜0.01）;高脂运动组显著高于对照组.3）高脂组肝小叶结构模糊,肝窦界限不清,汇管区结构模糊,肝细胞肿胀,有空泡样改变,肝脂肪变性.高脂运动组肝脏仍有脂肪积聚,但肝细胞空泡消失,呈好转趋势.4）高脂运动组MDA显著低于高脂组（P＜0.01）;高脂运动组SOD显著高于高脂组（P＜0.01）.结论：运动可以通过上调PPARαmRNA来促进脂肪酸氧化、降低血脂,从而有效预防肝细胞脂肪变性.     

大鼠酒精性肝损伤模型及蛋白表达指纹图谱的建立

目的:建立大鼠酒精性肝损伤模型,以蛋白质芯片技术为实验手段对损伤过程中的大鼠血清及肝脏蛋白质变化进行观察,以期获得损伤过程中的蛋白标志物,建立损伤过程蛋白表达指纹图谱;观察有机硒对大鼠肝脏损伤的防护作用。方法:用食用酒精辅以橄榄油对大鼠进行肝损伤,动态检测大鼠肝重比、血清生化指标,并进行肝组织病理切片观察;应用表面加强激光电离解吸飞行时间质谱技术对大鼠肝损伤过程进行跟踪检测,获得蛋白标志物,同时证实有机硒对肝损伤具有一定的防护作用。结果:肝重比、生化指标及病理切片均表明损伤模型已基本建立,同时验证了有机硒的肝损伤保护作用。在12周的损伤过程中,发现大鼠血清中有4个具有统计学意义的蛋白标志物,其相对分子质量(Mr)分别为7010、8307、11624和14041;在肝组织中发现了2个有统计意义的蛋白标志物,其Mr分别为5931.2和7104.6。结论:建立了大鼠酒精性肝损伤模型,获得了血清及肝脏蛋白标志物,为后期进行临床实验提供了可行的研究方法;同时为有机硒应用于临床进行肝损伤防护奠定了良好的实验基础。     

青藤碱抗大鼠肝脏缺血/再灌注损伤作用的机制探讨

目的:观察青藤碱时大鼠肝脏缺血再灌注损伤的影响,探讨其保护大鼠肝脏缺血再灌注损伤作用的机制.方法:通过建立大鼠全肝缺血再灌注损伤模型,应用硝酸酶还原法测定肝脏缺血再灌注后60min血清NO水平变化;测定再灌注60 min后肝组织内MDA和SOD含量变化;再灌注60min取肝组织完成肝组织显微结构的观察.结果:肝脏缺血再灌注损伤后血清NO水平降低;青藤碱能提高再灌注后血清NO水平,且能改善肝脏缺血再灌注损伤的微循环,减轻肝细胞内超微结构的损害程度.结论:青藤碱对大鼠肝脏缺血再灌注损伤有保护作用,其主要作用机制是清除氧自由基和改善微循环.     

黑果枸杞汁对大鼠酒精性肝损伤的保护作用*

目的: 研究黑果枸杞汁对大鼠酒精性肝损伤的保护作用,探讨其中Toll样受体4(TLR4)/p38 丝裂原活化蛋白激酶(p38 MAPK)信号通路的调节机制。方法: 60只雄性SD大鼠随机分为空白对照组(C)、模型组(M)、低剂量黑果枸杞汁组(LLM)、中剂量黑果枸杞汁组(MLM)、高剂量黑果枸杞汁组(HLM),每组12只。M、LLM、MLM和HLM组每天以20 ml/kg(8 g/(kg·d))剂量分2次灌胃400 g/L酒精,C组于相同时间点灌胃等体积蒸馏水。每日首次酒精灌胃前4 h,黑果枸杞汁各剂量组分别以2.4、4.8、9.6 ml/(kg·d)进行灌胃,其他组于相同时间点灌胃等体积蒸馏水。实验周期4周,末次实验结束后24 h处死大鼠,取血液和肝脏,计算肝脏指数,HE染色观察肝脏组织形态,比色法检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)活性,免疫组化法检测肝脏TLR4、p38 MAPK及磷酸化p38 MAPK(p-p38 MAPK)蛋白质表达,酶联免疫吸附试验检测肝脏肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-10(IL-10)、白细胞介素-18(IL-18)水平。结果: 与C组比较,M组成功建立酒精性肝损伤模型。与M组比较,黑果枸杞汁各剂量组的相关指标出现改善,其中HLM组肝脏组织形态改善最为显著,其肝脏系数、血清ALT和AST、肝脏TLR4蛋白质表达、p-p38 MAPK/p38 MAPK比值、TNF-α、IL-1β和IL-18水平均显著降低(P＜0.05或P＜0.01),肝脏IL-10水平显著升高(P＜0.01)。黑果枸杞汁各剂量组组间比较,肝脏系数、血清AST、肝脏TLR4蛋白质表达、p-p38 MAPK/p38 MAPK比值、TNF-α和IL-18水平,HLM组较LLM组均显著降低(P＜0.05或P＜0.01);肝脏IL-10水平,HLM组较LLM和MLM组均显著升高(P＜0.05或P＜0.01);其余主要指标组间比较均无统计学差异(P＞0.05)。结论: 黑果枸杞汁可以通过调控TLR4/p38 MAPK信号通路,改善炎症应激,缓解大鼠酒精性肝损伤,高剂量组效果优于其他剂量组。     

原代培养大鼠脂肪前体细胞分化过程中PPARγ和C/EBPαmRNA的表达(简报)

脂肪前体细胞是一类具有增殖分化能力的单能干细胞,在体内多种因素的影响下,脂肪前体细胞聚脂分化为成熟脂肪细胞。研究表明,脂肪前体细胞的聚脂分化过程受到一系列基因的调控,其中.过氧化物酶体增殖体激活受体(peroxisome prolifera- tors-activated receptor gamma,PPARγ)与CCAAT增强子结合蛋白α(CCAAT/enhancer binding protein al-     

牛磺酸对肢体缺血／再灌注后肝损伤大鼠TNF-α、NF-κB表达的影响

目的：探讨给予牛磺酸预处理对肢体缺血／再灌注（limb ischemia-reperfusion,H／R）后大鼠肝脏损伤及,INn、NF—KB表达的影响及意义。方法：采用Wistar大鼠建立LI/R损伤模型,随机分为4组（n=10）：对照（C）组,缺血／再灌注（I／R）组,牛磺酸（T）组和牛磺酸＋缺血／再灌注（TR）组。比色法测定动物血浆ALT、AST、MDA,肝组织MDA、MPO、DNA裂解率和钙含量,放免法检测血浆及肝组织TNF-α水平;HE染色观察肝脏组织形态改变;免疫组化法观察NF-κB蛋白表达。结果：与C组比较,I／R和TR组各损伤性指标、TNF-α水平均升高,NF-κB蛋白表达增高（P〈0．01）;但TR组上述各项指标较I／R组显著降低。结论：牛磺酸预处理可减轻大鼠LI／R所致肝脏损伤,降低TNF-α、NF-κB表达。     

茶多酚对慢性酒精中毒大鼠肝损伤的保护作用

目的：建立慢性酒精诱导的成年大鼠肝损伤动物模型,并进行茶多酚的干预,观察茶多酚的干预对慢性酒精诱导的肝损伤大鼠的防护作用及其可能的机制。方法：将36只SD大鼠适应性喂养一周后,随机分为对照组、酒精损伤组和茶多酚干预组（每组12只）。对照组大鼠用0.9%生理盐水按7 g/kg灌胃,酒精组用体积分数56%的红星牌白酒同剂量灌胃,茶多酚干预组在酒精灌胃同时给予0.25 g/kg剂量的茶多酚。每天定时灌胃一次,连续8周。8周后处死大鼠,取内脏脂肪和肝脏组织,以脂体比衡量内脏脂肪含量,以肝体比和油红O染色结果衡量肝脂质沉积,测定超氧化物歧化酶（SOD）活力、丙二醛（MDA）含量、总抗氧化能力（T-AOC）和谷胱甘肽过氧化物酶（GSH-Px）活力等氧化应激指标,测定肝脏组织中脂肪酸转位酶（FAT/CD36）蛋白水平。结果：与对照组相比,酒精损伤组大鼠内脏脂肪含量、SOD/MDA比值、T-AOC和GSH-Px活力显著下降（（P<0.05或P<0.01）,肝体比、FAT/CD36蛋白水平显著提高（P<0.01）,肝细胞中脂滴增加;与酒精损伤组相比,茶多酚干预组大鼠内脏脂肪含量、SOD/MDA比值、T-AOC和GSH-Px活力显著增加（（P<0.05或P<0.01）,肝体比、FAT/CD36蛋白水平显著下降（P<0.01）,肝细胞中脂滴减少。结论：茶多酚干预能改善慢性酒精中毒大鼠肝脏的脂质沉积和氧化应激状态,并伴有肝细胞膜上FAT/CD36表达的减少。     

Snail1基因表达在妊娠期糖尿病大鼠氧化应激及肝脏损伤的作用机制

摘要 目的：探讨Snail1基因表达在妊娠期糖尿病大鼠氧化应激及肝脏损伤的作用机制。方法：健康成年C57BL/6雌性大鼠32只作为研究对象。采用高脂喂养联合小剂量链脲佐菌素注射的方式构建妊娠期糖尿病大鼠模型。将所有大鼠分为正常妊娠组,正常妊娠+Snail1过表达组,妊娠期糖尿病组,妊娠期糖尿病+Snail1过表达组。采用qRT-PCR检测大鼠Snail1的mRNA表达水平,并检测大鼠妊娠期体重、氧化应激指标、炎症指标和肝功能指标。结果：与正常妊娠组相比,正常妊娠+Snail1过表达组、妊娠期糖尿病组、妊娠期糖尿病+Snail1过表达组的孕鼠体重、胎鼠体重、胎盘重量、Snail1 mRNA,明显更高（P＜0.05）,且妊娠期糖尿病+Snail1过表达组孕鼠体重、胎鼠体重、胎盘重量、Snail1 mRNA均显著高于正常妊娠+Snail1过表达组和妊娠期糖尿病组（P＜0.05）;与正常妊娠组相比,正常妊娠+Snail1过表达组、妊娠期糖尿病组、妊娠期糖尿病+Snail1过表达组的FBG、FINS、HOMA-IR明显更高（P＜0.05）,且妊娠期糖尿病+Snail1过表达组FBG、FINS、HOMA-IR均显著高于正常妊娠+Snail1过表达组和妊娠期糖尿病组（P＜0.05）;与正常妊娠组相比,正常妊娠+Snail1过表达组、妊娠期糖尿病组、妊娠期糖尿病+Snail1过表达组的ROS、GSH-Px、MDA明显更高（P＜0.05）,且妊娠期糖尿病+Snail1过表达组ROS、GSH-Px、MDA均显著高于正常妊娠+Snail1过表达组和妊娠期糖尿病组（P＜0.05）;与正常妊娠组相比,正常妊娠+Snail1过表达组、妊娠期糖尿病组、妊娠期糖尿病+Snail1过表达组的TNF-α、IL-1β、IL-18明显更高（P＜0.05）,且妊娠期糖尿病+Snail1过表达组TNF-α、IL-1β、IL-18均显著高于正常妊娠+Snail1过表达组和妊娠期糖尿病组（P＜0.05）;与正常妊娠组相比,正常妊娠+Snail1过表达组、妊娠期糖尿病组、妊娠期糖尿病+Snail1过表达组的GPT、GOT、ALP明显更高（P＜0.05）,且妊娠期糖尿病+Snail1过表达组GPT、GOT、ALP均显著高于正常妊娠+Snail1过表达组和妊娠期糖尿病组（P＜0.05）。结论：妊娠期糖尿病大鼠Snail1基因的表达上调可加重糖脂代谢紊乱,并激活下游氧化应激和炎症反应,进而加重大鼠肝脏损伤。     

酒精性肝病与肠道菌群关系的研究进展

肠道菌群被认为是人体的"第二大脑",肝脏被称为人体内的"生化工厂",由于肠道与肝脏均起源于内胚层,且通过门静脉紧密相连,所以肝脏的各项机能都与肠道菌群息息相关。酒精性肝病是由于摄入酒精导致的慢性肝病之一,在全球范围内普遍存在。近年来的研究结果表明,酒精性肝病(alcoholic liver disease,ALD)的发生与发展与肠道菌群密切相关。本文就肠道菌群与ALD的关系作一综述,并对靶向肠道菌群治疗ALD的方法简要总结,以期对ALD的治疗提供新策略。     

腺苷蛋氨酸预防酒精性肝病及其作用机制探讨

目的探讨腺苷蛋氨酸(SAM)防治大鼠酒精性肝病的作用机制。方法健康雄性wistar大鼠30只,随机分为对照组、模型组和SAM干预组。模型组大鼠采用逐渐增加浓度(30%-60%)和剂量(5-9g·kg-1·d-1)的方法酒精灌胃16周,干预组增加SAM(100mg/kg)灌胃,其它同模型组。16周末随机处死动物,检测血清总同型半胱氨酸(tHcy)的浓度和肝组织胱硫醚β合成酶(CBS)的活性;分别采用免疫组化方法和RT-PCR法检测肝组织中GRP-78、calpain 2及其caspase-12的表达;采用TUNEL染色法检测肝细胞凋亡。结果模型组大鼠16周末出现肝细胞弥漫小泡性脂肪变性,窦周纤维化,汇管区纤维组织增生并有纤维间隔形成。SAM组病理改变较模型组明显减轻。SAM组血清tHcy的浓度(7.00±0.79)较模型组(9.85±0.12)明显降低,而CBS的活性(511.60±57.44)较模型组(390.45±31.17)升高,F值分别为147.28和41.14,P值均<0.01;免疫组化和RT-PCR结果显示SAM组GRP-78、Calpain 2、caspase-12的表达较模型组减弱;SAM组的肝细胞凋亡指数(31.24±2.65)较模型组(65.71±9.78)降低,F值为301.79,P<0.01。结论在大鼠酒精性肝病中,腺苷蛋氨酸通过提高胱硫醚β合成酶活性,改善内质网应激,减少肝细胞凋亡,减轻肝脏损伤。     

MicroRNA-200a induces apoptosis by targeting ZEB2 in alcoholic liver disease

Alcoholic liver disease (ALD) and its complication continued to be a major health problem throughout the world. Increasing evidence suggests that microRNA (miRNA) that regulate apoptosis, inflammation and lipid metabolism are affected by alcohol in ALD. MiR-200a has emerged as a major regulator in several liver diseases, but its role in ALD has not been elucidated. The aim of this study is to figure out the biological function of miR-200a in ALD and to explore its underlying mechanism. The expression pattern of miR-200a were analyzed in vitro and in vivo, we showed that miR-200a was up-regulated in ALD in AML-12 and primary hepatocyte. We then examined it's effect on cell apoptosis and identified zinc finger E-box binding homeobox 2 (ZEB2; also known as SIP1) as a direct target gene of miR-200a. Furthermore, reintroduction of ZEB2 could reverse the pro-apoptosis of miR-200a on AML-12. Taken together, our study demonstrated that miR-200a regulates the apoptosis of hepatocyte in ALD by directly target ZEB2, both of which could serve as new therapeutic targets for ALD.     

补锌对酒精性肝病的影响及其分子机制

目的:本研究是为了观察饮食补充锌减轻酒精性肝病损伤的作用及与HNF-4α的关系。方法:选用成年C57BL/6小鼠40只,按随机数字表分为4组(n=10):正常对照组、酒精中毒组、正常补锌组及酒精补锌组,用不同饮食喂养6个月处死,在正常补锌组和酒精补锌组小鼠饮用水中加入硫酸锌,使锌的含量达到75 mg/L。取各组小鼠肝组织进行病理切片及增殖细胞核抗原(PCNA)免疫组织化学染色,RT-PCR检测肝细胞核因子-4α(HNF-4α)含量,Western blot检测肝组织HNF-4α蛋白表达,检测"肝组织超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量"。结果:酒精中毒组小鼠HNF-4α转录及表达均明显低于正常对照组,差异具有统计学意义(P<0.05),该组小鼠MDA含量增高,SOD活性下降与正常对照组相比差异有统计学意义(P<0.05);而酒精补锌组小鼠PCNA阳性肝细胞数目及HNF-4α蛋白表达水平明显高于酒精中毒组,差异有统计学意义(P<0.05),该组小鼠SOD活性增加,MDA下降,与酒精中毒组相比差异有统计学意义(P<0.05)。结论:长期酒精喂养导致小鼠氧化还原失衡,而补锌可逆转该状态。我们推测饮食补锌可能是通过增加HNF-4α的转录及表达而增强酒精喂养小鼠的肝再生,因此,饮食补锌可能对酒精性肝病有较好的影响。     

超声在评价大鼠酒精性脂肪肝模型中的应用

目的利用超声技术来评价大鼠酒精性脂肪肝动物模型。方法选取40只SD大鼠随机分为两组（n=20只）。模型组按每周测定的体重早晚各1次乙醇灌胃（10 g/kg）,第1周浓度为40%,第2、3周分别为45%和50%,第4周为55%灌胃直至12周;对照组给予等体积的生理盐水灌胃。造模于第4、8和12周时对两组大鼠进行超声监测,并从两组中各随机抽取3只大鼠进行肝脏病理学分析,与超声监测结果进行对比分析。结果超声与病理检查结果均提示酒精性脂肪肝造模成功,超声可以监测模型组大鼠肝脏脂肪病变从轻到重的渐变过程以及对照组大鼠无脂肪病变过程。这与肝组织的病理学诊断结果具有一致性。结论超声检测技术可以较好地进行活体评价大鼠酒精性脂肪肝动物模型。     

Oxidative stress-mediated aldehyde adduction of GRP78 in a mouse model of alcoholic liver disease: functional independence of ATPase activity and chaperone function

Pathogenesis in alcoholic liver disease (ALD) is complicated and multifactorial but clearly involves oxidative stress and inflammation. Currently, conflicting reports exist regarding the role of endoplasmic reticulum (ER) stress in the etiology of ALD. The glucose-regulated protein 78 (GRP78) is the ER homolog of HSP70 and plays a critical role in the cellular response to ER stress by serving as a chaperone assisting protein folding and by regulating the signaling of the unfolded protein response (UPR). Comprising three functional domains, an ATPase, a peptide-binding, and a lid domain, GRP78 folds nascent polypeptides via the substrate-binding domain. Earlier work has indicated that the ATPase function of GRP78 is intrinsically linked and essential to its chaperone activity. Previous work in our laboratory has indicated that GRP78 and the UPR are not induced in a mouse model of ALD but that GRP78 is adducted by the lipid electrophiles 4-hydroxynonenal (4-HNE) and 4-oxononenal (4-ONE) in vivo. As impairment of GRP78 has the potential to contribute to pathogenesis in ALD, we investigated the functional consequences of aldehyde adduction on GRP78 function. Identification of 4-HNE and 4-ONE target residues in purified human GRP78 revealed a marked propensity for Lys and His adduction within the ATPase domain and a relative paucity of adduct formation within the peptide-binding domain. Consistent with these findings, we observed a concomitant dose-dependent decrease in ATP-binding and ATPase activity without any discernible impairment of chaperone function. Collectively, our data indicate that ATPase activity is not essential for GRP78-mediated chaperone activity and is consistent with the hypothesis that ER stress does not play a primary initiating role in the early stages of ALD.     

Ameliorative effects of autophagy inducer,simvastatin on alcohol-induced liver disease in a rat model

Alcoholic liver disease (ALD) encompasses a variety of liver injuries with various underlying mechanisms but still no effective treatment. So we aimed to monitor the influence of simvastatin on alcohol-induced liver injury and elucidate the underlying mechanisms of its cytoprotective effect. Thirty male albino rats were randomly divided into five equal groups. Group 1 (control): received a standard diet; group 2: received simvastatin (10 mg kg⁻¹ day ⁻¹) once a day orally for 8 weeks; group 3: received 20% ethanol (7.9 g kg ⁻¹ day ⁻¹) daily orally for 8 weeks; group 4: received 20% ethanol along with same simvastatin dose daily for 8 weeks; group 5: received 20% ethanol orally for 8 weeks then received the same simvastatin dose for the next 8 weeks. Serum alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol were measured. Liver tissue malondialdehyde, reduced glutathione levels, and superoxide dismutase activity were estimated. B-cell lymphoma 2 and C/EBP homologous protein levels were evaluated by enzyme linked immunosorbent assay (ELISA). Light chain 3-II and peroxisome proliferation-activated receptor gamma messenger RNA expression was assessed by real-time polymerase chain reaction. Immunohistochemical staining was performed using anti-rat tumor necrosis factor-alpha antibody. Our results revealed that simvastatin treatment was able to ameliorate alcohol-induced liver damage; the improved biochemical data were confirmed by histopathological evaluation. Simvastatin being an autophagy inducer was able to prevent and reverse alcohol-induced liver changes via induction of autophagy, attenuation of oxidative stress, inflammation, and endoplasmic reticulum stress-induced apoptosis. Therefore, our findings suggest that treatment with simvastatin may be a useful approach in the management strategy of ALD.     

Noncoding RNAs in alcoholic liver disease

Alcoholic liver disease (ALD) is a complex process with high morbitity and can cause liver dysfunction, which contains a wide spectrum of hepatic lesions, including steatohepatitis, fibrosis, cirrhosis, and eventually hepatocellular carcinoma. To date, the molecular mechanisms for ALD have not been fully explored and an effective therapy is still missing. Overwhelming evidence shows dysregulation of noncoding RNAs (ncRNAs), particularly microRNAs (miRNAs), is correlated with etiopathogenesis and progress of ALD including hepatocyte damage, disrupted lipid metabolism, aggressive inflammatory responses, oxidative stress, programmed cell death, fibrosis, and epigenetic changes induced by alcohol. For example, circulating miRNA-122 is a marker of hepatocyte damage, and miRNA-155 is a potential marker of inflammation, indicating their diagnosis therapeutic potential in ALD. In addition, roles for long noncoding RNAs (lncRNAs) and circular RNAs in ALD are being uncovered. Further, circulating ncRNAs and exosome-derived ncRNAs have attracted more attention lately, suggesting a role in the prevention and treatment of ALD. This review covers the roles of ncRNAs in ALD, and the potential uses as markers for diagnosis and therapeutic options.     

MicroRNAs in alcoholic liver disease: Recent advances and future applications

Alcoholic liver disease (ALD) is characterized by hepatocyte damage, inflammatory cell activation, and increased intestinal permeability leading to the clinical manifestations of alcoholic hepatitis. Selected members of the family of microRNAs (miRNAs) are affected by alcohol, resulting in an abnormal miRNA profile in the liver and circulation in ALD. Increasing evidence suggests that miRNAs that regulate inflammation, lipid metabolism and promote cancer are affected by excessive alcohol administration in mouse models of ALD. This communication highlights recent findings in miRNA expression and functions as they relate to the pathogenesis of ALD. The cell-specific distribution of miRNAs, as well as the significance of circulating extracellular miRNAs, is discussed as potential biomarkers. Finally, the prospects of miRNA-based therapies are evaluated in ALD.