柴苓调肝颗粒对非酒精性脂肪性肝病大鼠肝组织肿瘤坏死因子-α及瘦素基因表达的影响

目的:通过实验研究观察柴苓调肝颗粒对非酒精性脂肪性肝病(NAFLD)大鼠肝组织肿瘤坏死因子(TNF)-α、瘦素(LP)基因表达的影响,探讨其治疗作用机制。方法:以喂高脂饲料的方法制备大鼠NAFLD模型,造模成功后,随机分为8组,柴苓调肝颗粒高、中、低剂量组,甘乐对照组、三七脂肝丸对照组、模型对照组、饮食控制组和正常对照组。观察实验大鼠治疗前后一般状态及病理改变;采用免疫组化二步法检测肝组织中的TNF-α,CYP2E1蛋白的表达;实时荧光定量聚合酶链反应(Real Time-PCR,RT-PCR)法检测肝组织中的TNF-αmRNA和LPmRNA表达水平。结果:柴苓调肝颗粒高剂量组大鼠各项指标与模型对照组和饮食控制组比较差异均有显著性意义(P<0.05或P<0.01),与正常对照组比较差异无统计学意义(P﹥0.05)。结论:柴苓调肝颗粒可以减轻大鼠体重,降低肝组织中TNF-α、CYP2E1含量及蛋白表达量,降低肝组织中的TNF-α和LP mRNA表达水平,使肝组织病理学改变减轻并且趋于正常。其作用机制可能与柴苓调肝颗粒能够调节脂代谢相关的TNF-α和LP有关。     

壳聚糖治疗大鼠非酒精性脂肪性肝病的初步实验研究

目的探索不同剂量壳聚糖治疗非酒精性脂肪性肝病的效果。方法60只大鼠随机分为空白对照组（10只）、脂肪肝模型组（20只）和3个不同剂量壳聚糖治疗组（各10只）。脂肪肝模型组和治疗组先用高脂饲料（含88％普通饲料＋10％猪油＋2％胆固醇）喂养12周。壳聚糖治疗组在13～20周每日经灌胃给予相对分子质量为127100壳聚糖溶液1次。三组的剂量分别为每公斤体质量0．094g、0．188g和0．375g。20周时处死动物,分别取肝组织切片观察脂肪变、炎症和纤维化情况,血清行生化指标检测。结果模型组动物均形成F4级脂肪变、G1～G2炎症和S1～S2纤维化。模型组动物ALT、AST、ALP、TC和LDL均较空白对照组显著升高。TG增高和HDL降低差异无统计学意义。与模型组相比,壳聚糖治疗各组大鼠肝脂肪变和炎症差异无统计学意义;但治疗组肝纤维化有明显好转。大剂量壳聚糖治疗组中60％大鼠肝纤维化减轻到S0期,无S2期。壳聚糖治疗组的生化指标也有一定程度的好转,但未恢复到空白对照组水平。结论大剂量壳聚糖（每日0．375g／kg）对改善大鼠肝组织的脂肪肝和纤维化有明显效果,对生化指标改善也有一定效果。     

调脂药物在非酒精性脂肪性肝病中的应用

非酒精性脂肪性肝病（NAFLD）是指除外酒精和其他明确的损肝因素所致的、以弥漫性肝细胞大泡性脂肪变为主要特征的临床病理综合征,包括单纯性非酒精性脂肪肝（NAFL）以及由其演变的脂肪性肝炎（NASH）和肝硬化.研究表明非酒精性脂肪肝是不明原因转氨酶升高的主要原因之一。欧洲和日本普通成人脂肪肝患病率在14％～21％。     

柴苓调肝颗粒对非酒精性脂肪性肝病胰岛素抵抗机制的探讨

[目的]探讨柴苓调肝颗粒治疗非酒精性脂肪肝病(NAFLD)的作用机制.[方法]将造模成功的63只雄性Wistar大鼠随机分成7组,每组9只,分别为模型组,饮食控制组,甘乐对照组,三七脂肝丸对照组,柴苓调肝颗粒高、中、低剂量组,未造模的9只大鼠为正常对照组;检测各组的血糖、血胰岛素、肝脏SOCS-3mRNA和SREBP-1c mRNA表达.[结果]与正常对照组相比,模型组血糖、血胰岛素、肝组织S)CS-3mRNA、SREBP-1c mRNA表达显著上调;柴苓调肝颗粒高、中、低剂量组SOCS-3mRNA、SREBP-1cmRNA表达较模型组下调,且血糖、血胰岛素水平下降;用药各组间比较,差异无统计学意义.SOC-3mRNA表达水平与胰岛素抵抗指数、SREBP-1c mRNA表达水平呈显著正相关.[结论]SO)C-3可能通过胰岛素抵抗及上调肝组织SREBP-1c mRNA表达参与NAFLD发病,柴苓调肝颗粒能抑制肝脏SO)C-3 mRNA及的SREBP-1c mRNA表达,对NAFLD有一定治疗作用.     

非酒精性脂肪性肝病治疗进展

非酒精性脂肪性肝病(non-alcoholic fatty liver disease, NAFLD)已成为目前全球最主要的慢性肝病病因,是当前研究的热点问题,其预防和治疗也成了研究的重点和难点,目前尚无批准上市的特异性药物及明确的治疗方案,本文针对NAFLD的相关治疗及新兴靶向药物作一概述,给临床医师提供参考。     

非酒精性脂肪性肝病治疗进展

非酒精性脂肪性肝病无特效治疗方法,目前以生活方式调节为基础,必要时辅以药物治疗。本文从生活方式调节和药物治疗两方面回顾近年来的治疗研究进展。     

非酒精性脂肪性肝病治疗策略

非酒精性脂肪性肝病（NAFLD）是指除外酒精和其他明确的损肝因素所致的,以弥漫性肝细胞大泡性脂肪变为主要特征的临床病理综合征,包括单纯性脂肪肝以及由其演变的非酒精性脂肪性肝炎（NASH）和肝硬化。在欧美等发达国家,NAFLD发病率可达到20％～30％,在亚太地区成人NAFLD患病率亦达到12％～24％,而且目前仍呈上升趋势。     

非酒精性脂肪性肝病研究新进展

非酒精性脂肪性肝病( non- alcoholic fatty liver disease,NAFLD)是指除外酒精和其他明确的肝损害因素所致的,以弥漫性肝细胞大泡性脂肪变为主要特征的临床病理综合征,包括单纯性脂肪性肝病以及由其演变的脂肪性肝炎和肝硬化.NAFLD是21世纪全球重要的公共健康问题之一,也是常见的慢性肝病.     

非酒精性脂肪性肝病肝纤维化诊治研究进展

非酒精性脂肪肝（NAFLD）是指除外长期大量饮酒和其他损伤肝脏因素所引起的以肝脏脂肪沉积为主要表现的临床综合征,患者肝脏脂肪代谢功能出现明显障碍,使得大量脂肪类物质蓄积于肝细胞,导致肝细胞发生脂肪变性,从单纯性非酒精性脂肪肝（NAFL）发展到非酒精性脂肪性肝炎（NASH）,最终发展为肝纤维化、肝硬化和终末期肝病,甚至肝癌。近年来由于发病率逐渐升高引起人们的重视。     

药物治疗非酒精性脂肪性肝病进展

非酒精性脂肪性肝病(NAFLD)是发达国家引起肝功能异常最常见的原因,治疗的重点在于阻止疾病的进展,去除引起代谢综合征的危险因素,如肥胖、胰岛素抵抗及血脂紊乱等.随着NAFLD的发病机制逐渐揭示,可选择的治疗方法除减肥外,药物治疗有抗氧化剂、胰岛素增敏剂、降脂药和肝脏保护剂.本文重点对药物治疗的进展做一综述.     

复方甘枣宁预防大鼠非酒精性脂肪肝的实验研究

[目的]研究复方甘枣宁对高脂饮食诱发的大鼠脂肪肝的预防作用.[方法]采用高脂饲料喂饲制作大鼠非酒精性脂肪肝模型,同时以复方甘枣宁灌胃,12周后检测血清中总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、丙氨酸氨基转移酶(ALT)、天冬氨酸转氨酶(AST)水平,并作病理组织学观察,同时称体重、肝脏重,计算肝指数.[结果]复方甘枣宁明显减轻肝组织内脂肪变性,降低血清TC与AST水平.[结论]复方甘枣宁对高脂饮食诱发的大鼠非酒精性脂肪肝具有一定的预防作用.     

非酒精性脂肪性肝病的诊断和治疗进展

随着非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)流行率的上升以及对其危害的全面认识,其诊断和治疗发展迅速。本文介绍了新的NAFLD病理学评分系统和病理学检查指征;在无创性诊断方面概述了肝脏脂肪变性、肝脏炎症和纤维化无创性诊断的现有方法及最新进展,以及疾病进展风险因素;在治疗方面,描述了饮食控制要点,并介绍了抗阻运动联合有氧运动和避免静坐的三联运动方式;在药物治疗方面,介绍了维生素E和吡格列酮2个重点药物的优缺点。最后,简述了以疾病分级为基础的检测和治疗策略。     

活血化痰方对非酒精性脂肪肝大鼠炎性因子的影响

[目的]观察活血化痰方对非酒精性脂肪肝（NAFLD）大鼠炎性因子的影响。[方法]将30只大鼠随机分为正常对照组、模型组和活血化痰方组。检测各组大鼠血清中白细胞介素（IL）-6、IL-10及肿瘤坏死因子-α（TNF-α）的水平。[结果]与正常对照组比较,模型组血清中IL-6、TNF-α水平增高,血清中IL-10含量降低;与模型组相比,活血化痰方组血清中IL-6、TNF-α水平显著降低,血清中IL-10含量显著升高。[结论]活血化痰方可能通过降低血清中IL-6、TNF-α水平,提高血清中IL-10含量,调节体内炎性因子的变化,从而使NAFLD渐愈。     

非酒精性脂肪性肝病的研究进展

非酒精性脂肪性肝病经历由非酒精性单纯性脂肪肝发展至非酒精性脂肪性肝炎和肝硬化或原发性肝癌的缓慢过程,并与心血管病的发生关系密切.本文针对非酒精性脂肪性肝病的流行病学、发病机制、诊断和治疗等的研究进展进行综述.     

姜黄素对大鼠非酒精性脂肪肝的干预作用

[目的]研究姜黄素对大鼠非酒精性脂肪肝的保护作用。[方法]30只Wismr大鼠随机分为对照组、非酒精性脂肪肝模型组和姜黄素干预组。对照组以普通饲料饲养,模型组和干预组给予高脂饲料饲养,干预组每日予50mg／kg姜黄素灌胃,共计12周。实验结束处死大鼠,收集血清和肝组织。检测血清丙氨酸氨基转移酶活性、天冬氨酸氨基转移酶活性和血清总胆固醇含量,以及肝组织γ-谷氨酰转肽酶活性、三酰甘油含量、超氧化物歧化酶活性和谷胱甘肽活性。肝组织行苏木精-伊红染色和油红O染色检测肝脏病理改变。[结果]与模型组比较,干预组能显著降低丙氨酸氨基转移酶、天冬氨酸氨基转移酶和肝组织γ-谷氨酰转肽酶活性,减少血清总胆固醇和肝组织三酰甘油含量;显著升高肝组织超氧化物歧化酶和谷胱甘肽活性;明显减轻大鼠肝内脂肪沉积,改善肝细胞的脂肪性病理改变。[结论]姜黄素通过抗氧化作用,对大鼠非酒精性脂肪肝具有良好的干预作用。     

Current treatment of non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in Western World and frequently associated with insulin resistance and overweight and occurs often with type 2 diabetes. Interestingly, NAFLD is not only regarded as a hepatic component of the metabolic syndrome but also as an independent risk factor and a marker for increase in cardiovascular disease (CVD). Significantly, NAFLD is associated with an increased risk of all-cause mortality and predicts future CVD events independent of age, sex, LDL-cholesterol and features of metabolic syndrome. Although there was initial concern about drug toxicity with NAFLD, increasing evidence suggests that commonly used drugs such as metformin and statins do not cause harm and the thiazolidinediones (TZDs) may even confer a therapeutic benefit in NAFLD. Interestingly, medical and surgical treatments of obesity show potential benefit in treating NAFLD. In this review, we have focused on the safety and therapeutic impact of TZDs, statins, metformins and obesity medications in NAFLD. The potential benefit of bariatric surgery and the role of weight loss per se in treating NAFLD are also discussed.     

An update on non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in Asia

Introduction: Non-alcoholic fatty liver disease (NAFLD) has become the most overwhelming liver disease in Asia. In consideration of its increasing medical and economic impact on Asian people, it is time for us to review the update data in Asian countries and formulate strategies to cope with this emerging health problem in Asia. Moreover, growing data indicates that NAFLD may be a systemic disease, not just confined to liver-specific morbidity and mortality, but also associated with several extra-hepatic manifestations, such as cardiovascular diseases, chronic renal diseases, and malignancy. As the co-occurrence of NAFLD and viral hepatitis is common in Asia, issues related to the impact of NAFLD on the clinical outcomes and management of viral hepatitis remain to be elucidated.

Areas covered: In this article, a narrative review was conducted, searching for literature from PubMed, Ovid MEDLINE, and the Cochrane Library database till August 2016. Studies relevant to the emerging data of NAFLD in Asia, including the diagnosis, risk factors, the assessment and management of Asian NAFLD patients were examined and discussed.

Expert commentary: Collaboration in Asian countries to develop an effective and practical measurement to assess the severity of NAFLD is urgently required.     

Gut microbiota dysbiosis in patients with non-alcoholic fatty liver disease

BACKGROUND: Gut microbiota plays a significant role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). This study aimed to assess the contribution of gut microbiota dysbiosis to the pathogenesis of NAFLD. METHODS: Forty-seven human feces samples (25 NAFLD patients and 22 healthy subjects) were collected and 16S rDNA amplicon sequencing was conducted on Hiseq 2000 platform. Discrepancy of species composition between controls and NAFLD group was defined by Metastats analysis under P value<0.01. RESULTS: NAFLD patients harbored lower gut microbiota diversity than healthy subjects did. In comparison to the control group, the Proteobacteria (13.50%) and Fusobacteria (2.76%) phyla were more abundant in NAFLD patients. Ad-ditionally, the Lachnospiraceae (21.90%), Enterobacteriaceae (12.02%), Erysipelotrichaceae (3.83%), and Streptococcaceae (1.39%) families, as well as the Escherichia_Shigella (10.84%), Lachnospiraceae_Incertae_Sedis (7.79%), and Blautia (4.95%) genera were enriched in the NAFLD group. However, there was a lower abundance of Prevotella in the NAFLD group than that in the control group (5.83% vs 27.56%, P<0.01). The phylum Bacteroidetes (44.63%) also tended to be more abundant in healthy subjects, and the families Prevotellaceae (28.66%) and Ruminococcaceae (26.44%) followed the same trend. Compared to those without non-alcoholic steatohepa-titis (NASH), patients with NASH had higher abundance of genus Blautia (5.82% vs 2.25%; P=0.01) and the correspond-ing Lachnospiraceae family (24.33% vs 14.21%; P<0.01). Patients with significant fibrosis had a higher abundance of genus Escherichia_Shigella (12.53% vs 1.97%; P<0.01) and the corresponding Enterobacteriaceae family (13.92% vs 2.07%;P<0.01) compared to those with F0/F1 fibrosis. CONCLUSIONS: NAFLD patients and healthy subjects harbor varying gut microbiota. In contrast to the results of previous research on children, decreased levels of Prevotella might be detrimental for adults with NAFLD. The increased level of the genus Blautia, the family Lachnospiraceae, the genus Escherichia_Shigella, and the family Enterobacteriaceae may be a primary contributor to NAFLD progression.