硫酸软骨素对大鼠酒精性脂肪肝模型的影响

目的 观察硫酸软骨素对酒精性脂肪肝的治疗作用。方法 用连续灌服酒精的方法建立大鼠酒精性脂肪肝模型。在造模成功后给予硫酸软骨素治疗4周，观察一般情况及测定血清肝功能指标和血脂参数，并对大鼠肝脏行病理学检查。结果 连续灌服酒精8周后大鼠形成酒精性脂肪肝，给药4周后，硫酸软骨素（25mg/kg）组成显著降低血中丙氨酸氨基转移酶（ALT）和天门冬氨酸氨基转移酶（AST）活性与血中和肝脏中丙二醛（MDA），甘油三酯（TG），总胆固醇（TC）含量，改善肝脏炎症活动度与脂肪性变。结论 硫酸软骨素能改善酒精性脂肪肝大鼠体内脂质代谢，对酒精性脂肪肝具有一定的治疗作用。     

大鼠非酒精性脂肪肝造模方法的改进

目的:快速建立一种非酒精性脂肪肝大鼠模型.方法:24只♂SD大鼠随机平均分为正常组、常规组和改良组,分别喂普通基础饲料、常规用高脂饲料及常规高脂饲料 蔗糖 丙基硫氧嘧啶 胆酸钠.5 wk内动态观察三组大鼠的一般情况、体质量变化,均5 wk处死,观察大鼠肝脏病理形态变化,苏丹Ⅳ染色和电镜检测了解大鼠肝细胞胞质内脂滴存在情况,并比较三组大鼠血清甘油三酯(TG)、胆固醇(TC)、谷丙转氨酶(ALT)、谷草转氨酶(AST)水平、丙二醛(MDA)含量和超氧化物歧化酶(SOD)活力及肝组织甘油三酯(TG)、胆固醇(TC)含量的变化.结果:第4周开始正常组和改良组两组大鼠与常规组体质量之间有显著性差异(249.63±34.25,241.88±20.75 vs 275.38±6.59,P<0.05),改良组与正常组之间体质量无显著性差异(P>0.05).第5周在光镜下见改良组大鼠肝细胞内弥漫大量的脂肪空泡,电镜和苏丹Ⅳ染色证实肝细胞内有大量脂滴.肝脂肪变性程度为 ～ (H=13.36,P=0.0003),正常组和常规组大鼠肝细胞内未见明显脂肪变性.改良组大鼠血清TG,TC,ALT水平和MDA含量均高于正常组和常规组(TG:1.28±0.61 mmol/L vs 0.72±0.12,0.76±0.04 mmol/L;TC:12.78±1.47 mmol/L vs 1.71±0.03,2.31±0.49 mmol/ L;ALT:1518.64±186.04 nkat/L vs 1181.57±37.84,1262.92±159.20 nkat/L;MDA:13.40±4.24μmol/L vs 5.89±1.05,7.23±1.15μmol/L;均P<0.05),常规组与正常组比无显著差异(P>0.05);而改良组血清SOD活力显著低于正常组和常规组(5.21±0.81 nkat/mL vs 11.91±2.69,11.19±0.78 nkat/mL,P<0.05).肝组织TG,TC含量常规组和模型组均比正常组有增高(TG:2.14±0.26,5.83±1.42 mmol/L vs 1.20±0.16 mmol/L,P<0.05;TC:3.19±0.23,9.63±1.12 mmol/L vs 2.13±0.16 mmol/L,P<0.05),常规组与改良组也有显著差异(P<0.05).结论:通过与利用常规高脂饲料建模的方法比较,该改良方法5 wk成功地构建了非酒精性脂肪肝大鼠模型,缩短了建模时间,降低了实验成本且模型基本符合人类发病的自然状态,是一种理想的建模方式.     

甜菜碱对酒精性肝损伤大鼠凋亡基因caspase-12表达的影响

目的:研究甜菜碱对凋亡基因caspase-12表达的影响,探讨其抗酒精性肝损伤(ALD)大鼠肝细胞凋亡的机制.方法:采用酒精加鱼油灌胃配合高脂饮食建立酒精性肝损伤模型,应用半定量逆转录聚合酶链反应(RT-PCR)法和免疫组化法检测大鼠肝组织凋亡基因caspase-12mRNA和蛋白水平.结果:与正常组比较,模型组大鼠肝组织caspase-12表达明显增强(mRNA:1.00vs0.18,P<0.01;蛋白:0.2969±0.0451vs0.0526±0.0234,P<0.01),但高、低剂量甜菜碱能抑制其表达(mRNA:0.10,0.12vs1.00,P<0.01;蛋白:0.1215±0.0130,0.1850±0.0085vs0.2969±0.0451,P<0.01).甜菜碱高、低剂量组之间有显著差异(mRNA:0.10vs0.12,P<0.05;蛋白:0.1215±0.0130vs0.1850±0.0085,P<0.05).结论:甜菜碱能抑制凋亡基因caspase-12mRNA和蛋白的表达,可能是其减少凋亡的机制之一.     

郁芝胶囊对大鼠酒精性脂肪肝组织形态的影响

目的探讨郁芝胶囊对大鼠酒精性脂肪肝组织形态的影响。方法 60只大鼠随机分为6组,每组10只,即对照组、模型组、阳性药硫普罗宁组(40 mg/kg)、郁芝胶囊低、中、高剂量组(100、200、400 mg/kg)。模型组每天给予45%酒精、0.5 ml/100 g灌胃,对照组给予等量的生理盐水灌胃。造模第9周灌胃给予郁芝胶囊和硫普罗宁片进行治疗,连续4 w,末次给药12 h后去肝脏,称重后固定,行HE染色。结果与模型组相比,郁芝胶囊低、中、高剂量组大鼠在活动性和毛色方面均有改善;肝重比显著降低;光学显微镜下观察郁芝胶囊低、中、高剂量组大鼠肝组织内脂滴明显减少,肝细胞结构及排列明显改善。结论郁芝胶囊对酒精性脂肪肝有一定的治疗作用。     

甜菜碱对非酒精性脂肪性肝炎大鼠胰岛素抵抗的影响

目的:观察甜菜碱对非酒精性脂肪性肝炎(NASH)大鼠胰岛素抵抗的影响,探讨其可能的机制。方法:32只雄性Wistar大鼠随机分为正常对照组、模型组、甜菜碱低剂量和高剂量组。除正常对照组外,所有大鼠均饲以高脂肪饲料(加入脂肪肝诱导剂丙基硫氧嘧啶),构建NASH模型,甜菜碱低剂量和高剂量组大鼠分别以200mg/kg和400mg/kg剂量甜菜碱溶液灌胃。第12周末处死全部大鼠。测定血清糖(Glucose),应用ELISA检测血清胰岛素(In-sulin),计算胰岛素抵抗指数(IRI)。结果:甜菜碱显著降低血清Insulin(P0.01)、Glucose和IRI(P0.05),且低、高剂量组间与模型组比较差异均有显著性意义(P0.05)。结论:甜菜碱可防治大鼠NASH,机制之一可能为改善NASH大鼠胰岛素抵抗。     

甜菜碱对鹌鹑高脂饮食性脂肪肝的影响

背景：甜菜碱可改善酒精性肝病和非酒精性脂肪性肝病患者的血清生化指标和肝组织学变化，但其机制尚不明确。目的：研究甜菜碱对鹌鹁高脂饮食性脂肪肝的影响。方法：制备鹌鹁高脂饮食性脂肪肝动物模型，以甜菜碱干预后，观察其血清、肝脂质、肝功能生化指标和脂质过氧化指标的变化，并观察肝组织学改变。结果：予高脂饮食性脂肪肝鹌鹁甜菜碱0．2—0．8g／kg治疗6周后，其血清总胆固醇、三酰甘油、低密度脂蛋白．胆固醇、游离脂肪酸水平、肝重指数、肝组织总胆固醇均显著降低（P〈0．05或P〈0．01）；肝组织超氧化物歧化酶活性升高（P〈0．01）；0．8g/kg甜菜碱组可升高血清高密度脂蛋白．胆固醇水平（P〈0．05），降低肝组织三酰甘油和丙二醛含量（P〈0．01）。组织病理学检查结果显示，甜菜碱可使肝细胞脂肪变性程度明显减轻（P〈O．05或P〈0.01），0．8g／kg组的肝细胞结构趋于正常。结论：甜菜碱对鹌鹁高脂饮食性脂肪肝有较好的治疗作用，其部分机制可能是通过抗脂质过氧化和增加脂质代谢实现的。     

非酒精性脂肪肝动物模型造模方法的研究

脂肪肝是由多种疾病和多种病因引起的以肝脏脂肪蓄积过多为病理表现的一种常见肝病,部分病例可发展为肝纤维化,甚至导致肝硬化。近年来由于生活水平的提高、饮食结构的变化及预防保健措施的相对滞后,我国由高脂血症、肥胖、糖尿病、药物损害等引起的非酒精性脂肪肝发病率呈上升趋势。     

纳洛酮对酒精性脂肪肝大鼠作用探讨

目的　探讨纳洛酮对酒精性脂肪肝的作用及其可能机制。方法　将 48只Wistar雄性大鼠,随机分为 4组:酒精性脂肪肝模型组、纳洛酮低剂量处理组、纳洛酮高剂量处理组,正常对照组。4周末,处死所有大鼠,检测血液中天门冬氨酸氨基转移酶 (AST)、丙氨酸氨基转移酶(ALT)、谷光甘肽-S转移酶(GST)和β 内啡肽(β EP)含量。同时行肝脏病理组织学检查。结果　纳洛酮处理组血浆AST、ALT、GST和β EP含量明显低于模型组(P<0 05 ),但又高于正常对照组 (P<0 05 ),且处理组内部相比,差异也有显著性 (P<0 05)。病理检查发现处理组肝脏脂肪变程度明显轻于模型组。结论　纳洛酮可以通过降低血浆中β EP水平而具有防治酒精性脂肪肝的作用。     

郁芝胶囊对大鼠酒精性脂肪肝的治疗作用

目的探讨郁芝胶囊对酒精性脂肪肝模型大鼠的治疗作用。方法 60只大鼠随机分为6组,每组10只,即对照组、模型组、阳性药硫普罗宁组(40 mg/kg)、郁芝胶囊低、中、高剂量组(100 mg/kg、200 mg/kg、400 mg/kg)。模型组每天给予45%酒精,0.5 ml/100 g灌胃,对照组给予等量的生理盐水灌胃。造模第9周灌胃给予郁芝胶囊和硫普罗宁片进行治疗,连续4 w,末次给药12 h后腹主动脉取血,检测血清谷丙转氨酶(GPT)、谷草转氨酶(GOT)、总胆固醇(TC)、甘油三酯(TG)、超氧化物歧化酶(SOD)、丙二醛(MDA)水平。结果与模型组相比,郁芝胶囊低、中、高剂量组大鼠血清GPT、GOT、TC、TG和MDA均有不同程度降低(P<0.05或P<0.01),血清SOD含量显著升高(P<0.01)。结论郁芝胶囊对酒精性脂肪肝有一定的治疗作用。     

酒精性脂肪肝的治疗进展

酒精性脂肪肝（AFLD）是指长期饮酒导致的脂肪肝，是现在临床上最为常见的肝病之一。目前认为，酒精性脂肪肝治疗上主要有戒酒、营养及药物治疗等方法。近年来，有关这方面的研究很多，本文对此作以下阐述。     

非诺贝特治疗酒精性与药物性脂肪肝的实验研究

目的 研究非诺贝特对酒精性脂肪肝以及药物性脂肪肝的作用,并探讨两种脂肪肝的发病机制。方法 建立酒精性脂肪肝和药物性脂肪肝大鼠模型并分为治疗组(80 mg/kg)和对照组。4周后处死,分别测定肝功能,血清甘油三酯(TG)、胆固醇(TC)、高密度脂酯(HDL),血清及肝组织丙二醛(MDA)、肝脂酯(HL),脂蛋白脂酶(LPL)及肝脏病理变化。 结果 酒精性脂肪肝非诺贝特组与对照组比较,血清TG治疗组为(1.07±0.06)mmol/L,对照组为(1.56±0.29)mmol/L,血清MDA分别为(1.10±0.22)nmol/L和(1.26±0.21)nmol/L,肝组织内MDA分别为(5.92±1.24)nmol/g和(7.42±1.22)nmol/g,血清内HL分别为(0.053±0.006)μEq·ml-1·h-1和(0.037±0.006)μEq·ml-1·h-1,LPL水平明显升高分别为(0.018±0.004)μEq·ml-1·h-1和(0.014±0.004)μEq·ml-1·h-1;肝组织HL分别为(0.075±0.010)μEq·ml-1·h-1和(0.065±0.007)μEq·ml-1·h-1,LPL分别为(0.022±0.014)μEq·ml-1·h-1和(0.008±0.002)μEq·ml-1·h-1,TC的水平无明显变化,肝内脂质含量分别为(26.01±1.69)mg/g和(71.45±2.66)mg/g,同时肝脏病理明显改善。药物性脂肪肝非诺贝特组与对照组比较肝脏病理改变差异无显著意义。 结论 非诺贝特治疗酒精性脂肪肝可以明显减少肝内脂质的含量,改     

普罗布考类药物在治疗酒精性脂肪肝中的作用

目的探究普罗布考类药物在治疗酒精性脂肪性肝病中的作用,为临床应用普罗布考类药物治疗酒精性脂肪性肝病提供理论依据。方法构建酒精性脂肪性肝病大鼠模型。Wister大鼠普通饲料喂养1周后,随机分为空白对照组(12只)、实验组(24只)。空白对照组喂养普通饲料,实验组喂养普通饲料的同时加入酒精,5周后将实验组再随机分为药物组(12只,普罗布考,剂量1 mg/kg),非药物组(12只),共治疗5周。实验结束后,比较各组大鼠肝肿大程度、血清ALT、肝组织病理学评分。结果普罗布考明显减轻肝肿大(P<0.05),降低血清ALT(P<0.01),肝组织病理改善明显(减轻脂肪变性程度,P<0.01;减少小叶炎症数,P<0.001;减轻肝细胞气球样变性,P<0.05)。结论普罗布考在治疗大鼠酒精性脂肪肝中有效。     

Experimental models of metabolic and alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a multi-systemic disease that is considered the hepatic manifestation of metabolic syndrome (MetS). Because alcohol consumption in NAFLD patients is common, there is a significant overlap in the pathogenesis of NAFLD and alcoholic liver disease (ALD). Indeed, MetS also significantly contributes to liver injury in ALD patients. This “syndrome of metabolic and alcoholic steatohepatitis” (SMASH) is thus expected to be a more prevalent presentation in liver patients, as the obesity epidemic continues. Several pre-clinical experimental models that couple alcohol consumption with NAFLD-inducing diet or genetic obesity have been developed to better understand the pathogenic mechanisms of SMASH. These models indicate that concomitant MetS and alcohol contribute to lipid dysregulation, oxidative stress, and the induction of innate immune response. There are significant limitations in the applicability of these models to human disease, such as the ability to induce advanced liver injury or replicate patterns in human food/alcohol consumption. Thus, there remains a need to develop models that accurately replicate patterns of obesogenic diet and alcohol consumption in SMASH patients.     

Experimental study of osthole on treatment of hyperlipidemic and alcoholic fatty liver in animals

AIM: To evaluate the effects of osthole on fatty liver, and investigate the possible mechanism. METHODS: A quail model with hyperlipidemic fatty liver and rat model with alcoholic fatty liver were set up by feeding high fat diet and alcohol, respectively. These experimental animals were then treated with osthole 5-20 mg/kg for 6 wk, respectively. Whereafter, the lipid in serum and hepatic tissue, and coefficient of hepatic weight were measured. RESULTS: After treatment with osthole the levels of serum total cholesterol (TC), triglyceride (TG), lower density lipoprotein-cholesterol (LDL-C), coefficient of hepatic weight, and the hepatic tissue contents of TC and TG were significantly decreased. The activity of superoxide dismutase (SOD) in liver was improved. In alcohol-induced fatty liver rats, the level of malondialdehyde (MDA) in liver was decreased. In high fat-induced fatty liver quails, glutathione peroxidase (GSH-PX) in liver was significantly improved. The histological evaluation of liver specimens demonstrated that the osthole dramatically decreased lipid accumulation. CONCLUSION: These results suggested that osthole had therapeutic effects on both alcohol and high fat-induced fatty liver. The mechanism might be associated with its antioxidation.     

酒精性脂肪肝研究现状与进展

酒精性脂肪肝（AFLD）是指长期饮酒导致的脂肪肝，是目前临床上最为常见的肝脏疾病之一。本文主要目的是对AFLD的临床病理特点、发病机制以及可能的分子学机制进行综述，同时介绍目前治疗AFLD的策略。     

Significance of gut microbiota in alcoholic and non-alcoholic fatty liver diseases

Liver-gut communication is vital in fatty liver diseases, and gut microbes are the key regulators in maintaining liver homeostasis. Chronic alcohol abuse and persistent overnutrition create dysbiosis in gut ecology, which can contribute to fatty liver disease. In this review, we discuss the gut microbial compositional changes that occur in alcoholic and nonalcoholic fatty liver diseases and how this gut microbial dysbiosis and its metabolic products are involved in fatty liver disease pathophysiology. We also summarize the new approaches related to gut microbes that might help in the diagnosis and treatment of fatty liver disease.     

Comparative redox status in alcoholic liver disease and nonalcoholic fatty liver disease

Purpose Altered redox status has been implicated in pathogenesis of alcoholic liver disease (ALD) as well as in nonalcoholic fatty liver disease (NAFLD). This study was planned to find the relative role of redox status in these two diseases. Methods A total of 44 patients with ALD and 32 patients with NAFLD and 25 apparently healthy controls were included in the study. Redox status was estimated by measuring oxidative stress (superoxide dismutase (SOD) and lipid peroxidation products as thiobarbituric acid reactive substances (TBARS)) and antioxidant status (ferric reducing ability of plasma (FRAP) and vitamin C). Results TBARS level was raised significantly in both ALD (3.5 (2.3–9.4) vs. 1.8 (0.5–4.1) nmol/ml; P = 0.0001) and NAFLD (5.1 (1–10.2) vs. 1.82 (0.51–4.1) nmol/ml; P = 0.0001) as compared with controls, but was not different between ALD and NAFLD. SOD was significantly higher in ALD as compared to NAFLD (2.4 (1.3–7.8) vs. 0.68 (0.05–19.1) U/ml; P = 0.0001) and controls (1.12 (0.01–3.5) U/ml; P = 0.001). FRAP was lower in ALD as compared with NAFLD (345.4 (56–615.9) vs. 434.1 (197.6–733.3) μmol of Fe⁺² liberated; P = 0.001) but similar to that of controls (340.9 (141.5–697.5) μmol of Fe⁺² liberated). Conclusions ALD patients have a higher degree of redox imbalance as compared with NAFLD patients     

多烯磷脂酰胆碱联合水飞蓟素治疗酒精性脂肪肝的疗效观察

目的观察多烯磷脂酰胆碱联合水飞蓟素治疗酒精性脂肪肝的临床疗效。方法 72例酒精性脂肪肝患者随机分为治疗组(36例)和对照组(36例),治疗组给予多烯磷脂酰胆碱和水飞蓟素联合治疗;对照组仅给予甘草酸二铵治疗,疗程均为4周。治疗结束后比较两组治疗总有效率、肝功能指标、肝纤维化指标及药物不良反应。结果治疗组总有效率(86.1%)明显优于对照组(66.7%)(P<0.05);治疗结束后治疗组ALT、AST为(40.47±11.14)U/L和(54.14±10.71)U/L,较对照组显著降低(P<0.05);治疗结束后治疗组肝纤维化指标表达水平明显低于对照组(P<0.05);治疗期间两组均未见明显不良反应。结论多烯磷脂酰胆碱联合水飞蓟素治疗酒精性脂肪肝疗效显著,无明显副作用,值得临床推广应用。     

Clinical differences between alcoholic liver disease and nonalcoholic fatty liver disease

Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are serious health problems worldwide. These two diseases have similar pathological spectra, ranging from simple hepatic steatosis to steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. Although most subjects with excessive alcohol or food intake experience simple hepatic steatosis, a small percentage of individuals will develop progressive liver disease. Notably, both ALD and NAFLD are frequently accompanied by extrahepatic complications, including cardiovascular disease and malignancy. The survival of patients with ALD and NAFLD depends on various disease-associated conditions. This review delineates the clinical characteristics and outcomes of patients with ALD and NAFLD by comparing their epidemiology, the factors associated with disease susceptibility and progression, and the predictors and characteristics of outcomes. A comprehensive understanding of the characteristics and outcomes of ALD and NAFLD is imperative in the management of these chronic liver diseases.     

细胞因子在脂肪性肝病中的作用

无论是酒精性脂肪肝还是非酒精性脂肪肝,其发病机制都与细胞因子息息相关.此文综述了多种细胞因子在脂肪肝发生发展过程中的作用,以及其介导的细胞凋亡在脂肪肝发病机制中的作用,阐述了某些细胞因子对脂肪肝的治疗应用.