网络抗氧化剂对非酒精性脂肪性肝炎大鼠氧化应激作用的影响

目的探讨网络抗氧化剂对非酒精性脂肪性肝炎（NASH）大鼠氧化应激作用的影响。方法雄性SD大鼠30只,随机分为3组,正常对照组、模型组、网络抗氧化剂组。正常对照组普通饲料喂养,模型组喂高脂饮食,网络抗氧化剂组在高脂饮食12周后给予维生素E（100mg／kg）、维生素C（100mg／kg）、硫辛酸（40mg／kg）、辅酶Q10（100mg／kg）、还原性谷胱甘肽（100mg／kg）混合灌胃治疗。16周末处死各组大鼠,测定血清转氨酶（ALT、AST）及硒-谷胱甘肽过氧化物酶（Se-GSH-PX）活性,光镜下观察肝脏组织病理形态学改变,测定肝组织丙二醛（MDA）含量及超氧化物歧化酶（SOD）活性。结果与正常对照组比较,模型组大鼠血清ALT、AST显著升高（P〈0．05）;肝组织MDA含量增高（P〈0．05）,SOD及Se-GSH-PX活性下降（P〈0．05）;肝脏脂肪变性程度和炎症活动度均有显著增高（P〈0．05）,与模型组比较,网络抗氧化剂组可促进上述指标恢复（P〈0．05）。结论网络抗氧化剂对高脂饮食诱导的大鼠NASH有一定治疗效果,网络抗氧化剂之间协同增强的抗氧化能力有效阻遏了自由基引发的氧化应激,保持了氧化／抗氧化平衡,改善NASH大鼠脂肪变性,减轻炎症反应。     

非酒精性脂肪性肝炎的病理学诊断

非酒精性脂肪性肝病（NAFLD）是肝细胞脂肪变、小叶内和汇管区炎症、肝细胞损伤（如肝细胞气球样变和凋亡）以及纤维化等病变的不同组合。儿童NAFLD的肝脏组织学改变与成人有所不同。肝活检组织学检查是诊断NAFLD的金标准，可区分单纯性脂肪肝与非酒精性脂肪性肝炎（NASH）以及判断肝纤维化程度。本文主要介绍NAFLD肝组织活动性分级和纤维化分期的国际通用评分系统。     

多不饱和脂肪酸对非酒精性脂肪性肝炎大鼠肝组织脂肪细胞因子的影响

目的 观察多不饱和脂肪酸对非酒精性脂肪性肝炎(NASH)大鼠肝组织中瘦素、抵抗素和脂联素的影响.方法 将44只大鼠随机分为4组,对照组(10只)给予普通饲料喂养,模型组(10只)、低剂量组(12只)和高剂量组(12只)给予高脂饲料喂养制备NASH模型.低剂量组和高剂量组在喂养8周后加用ω-3多不饱和脂肪酸干预(0.5 ...     

罗格列酮预防非酒精性脂肪性肝炎大鼠肝纤维化的研究

目的观察罗格列酮预防非酒精性脂肪性肝炎（NASH）大鼠肝纤维化的作用。方法建立SD大鼠NAsH伴肝纤维化的模型（HF24w）,同时高脂喂养大鼠12周后予罗格列酮（1．5mg·kg^-1·d^-1）干预12周（HF24W＋RGZ12W组）。观察肝组织病理学改变,测定血清丙二醛（MDA）、肿瘤坏死因-α（TNF—α）、游离脂肪酸（FFA）、Ins、FPG,并计算胰岛素抵抗指数（HOMA—IR）。结果HF24W＋RGZ12W组肝组织炎症、纤维化评分明显低于HF24W组（P〈0．05）,脂肪变性与HF24W组无统计学差异;HF24W＋RGZ12W组血清MDA、TNF—α、FFA、Ins、HOMAIR均明显低于HF24W组（P〈0．05）。结论罗格列酮可以减缓NASH大鼠肝纤维化的发生发展。     

乳果糖对大鼠非酒精性脂肪性肝炎模型形成的影响

目的　探讨肠道环境改变与非酒精性脂肪性肝炎的关系。方法　 4 2只SD大鼠随机分为模型组 (n =2 4 )、治疗组 (n =12 )和正常组 (n =6 )。模型组和治疗组大鼠以高脂饲料喂养。治疗组大鼠高脂饮食 8周后以乳果糖治疗。正常组大鼠以正常饲料喂养。实验 8周处死 12只模型组大鼠 ,16周处死模型组剩余大鼠和治疗组、正常组大鼠。测定血清转氨酶 ,HE染色观察肝脏病理改变。结果　 16周模型组大鼠血清ALT、AST明显升高 ,肝脏表现为脂肪性肝炎 ,治疗组大鼠血清ALT、AST明显下降 ,接近正常组水平 ,肝组织炎症活动计数也明显下降 (5 .83± 2 .0 2比 3.6 3± 0 .6 4 ) ,但仍显著高于 8周模型组大鼠水平 (3.6 3± 0 .6 4比 1.98± 0 .90 )。治疗组肝细胞脂肪变性程度无显著变化。结论　乳果糖可以改善高脂饮食诱发的脂肪性肝炎大鼠肝组织炎症损伤 ,但不能完全阻止炎症的进展 ,提示肠道细菌过度生长等肠道环境的改变是非酒精性脂肪性肝炎发病的重要机制之一     

姜黄素防治大鼠非酒精性脂肪性肝炎的实验研究

非酒精性脂肪性肝炎(NASH)是继发于非酒精性脂肪肝病、合并肝脂肪变性与炎症的一种疾病,随着人民生活水平的提高,NASH的发病逐渐增多,防治本病已成为全球普遍关注的医学和社会问题。多年临床和实验研究表明,姜黄素具有抗肿瘤、抗突变、抗炎、抗氧化、保肝等广泛的药理作用[1]。本课题旨在通过建立大鼠非酒精性脂肪性肝炎模型,进一步明确姜黄素防治NASH的作用。1材料与方法1.1动物清洁级SD雄性大鼠,40只,体重(170~240)g,由湖北中医学院动物中心提供。普通饲料正常喂养一周后,随机分为4组,A组正常对照组、B组空白模型组、C组姜黄素防治…     

非酒精性脂肪性肝炎相关肝纤维化的研究现状

随着人们生活方式及饮食习惯的改变．非酒精性脂肪性肝病（NAFLD）的发病率正在逐年递增,在世界范围内成为慢性肝病的常见病因。美国近1／3年轻人患有NAFLD,而我国上海的发病率约占15％。NAFLD的发病率在肥胖、2型糖尿病（DM）、高血压、高脂血症等代谢综合征人群中更高。NAFLD包括单纯性脂肪肝、非酒精性脂肪性肝炎（NASH）和肝硬化。研究显示,单纯性脂肪肝预后较好,而NASH是肝纤维化的重要致病因子,NASH患者中有20％～40％进展至肝纤维化甚至肝硬化。     

节制饮食对大鼠非酒精性脂肪性肝炎的治疗作用

非酒精性脂肪性肝病 (nonalcoholicfattyliverdiseases ,NAFLD)可发展为肝纤维化和肝硬化 ,且经过非酒精性脂肪性肝炎 (nonalcoholicsteatohepatitis ,NASH )这一病理阶段[1 3 ] ,因而早期干预是必要的。然而至今尚无治疗NAFLD的特效药物 ,因此作为基本治疗的饮食疗法在NAFLD治疗中的作用越发受到重视。本研究将观察节制饮食对NASH的治疗作用。材料与方法一、材料雄性SD大鼠 2 0只 ,购自西普尔 必凯公司 ,体重 14 0～160 g ,正常喂养 1周后 ,通过高脂饮食 12周建立NASH大鼠模型 ,随机分为 2组 :模型组 10只继予高脂饮食喂养 ;…     

N-acetylcysteine attenuates oxidative stress and liver pathology in rats with non-alcoholic steatohepatitis

AIM To evaluate attenuating properties of N-acetylcysteine (NAC) on oxidative stress and liver pathology in rats with non-alcoholic steatohepatitis (NASH).METHODS Male Sprague-Dawley rats were randomly divided into three groups. Group 1 (control, n = 8) was free accessed to regular dry rat chow (RC) for 6 wk.Group 2 (NASH, n = 8) was fed with 100% fat diet for 6 wk. Group 3 (NASH NAC20, n = 9) was fed with 100% fat diet plus 20 mg/kg per day of NAC orally for 6 wk. All rats were sacrificed to collect blood and liver samples at the end of the study.RESULTS The levels of total glutathione (GSH)and hepatic malondialdehyde (MDA) were increased significantly in the NASH group as compared with the control group (GSH; 2066.7 ± 93.2 vs 1337.5 ± 31.5 μmol/L and MDA; 209.9± 43.9 vs 3.8 ±1.7 μmol/g protein, respectively, P ＜ 0.05). Liver histopathology from group 2 showed moderate to severe macrovesicular steatosis, hepatocyte ballooning, and necroinflammation.NAC treatment improved the level of GSH (1394.8 ± 81.2 μmol/L, P ＜ 0.05), it did not affect MDA (150.1 ± 27.0 μmol/g protein), but led to a decrease in fat deposition and necroinflammation.CONCLUSION NAC treatment could attenuate oxidative stress and improve liver histology in rats with NASH.     

茵栀黄口服液对非酒精性脂肪性肝炎大鼠肝脂肪变的保护作用研究*

目的 探讨茵栀黄口服液对蛋氨酸胆碱缺乏（MCD）饮食诱导的非酒精性脂肪性肝炎（NASH）大鼠肝脂肪变的保护作用。方法 将30只大鼠随机均分为对照组、MCD组和茵栀黄灌胃组。给予对照组普通饮食,给予另两组动物MCD饮食,于第4周末开始分别给予生理盐水或茵栀黄口服液灌胃,第8 w末处死大鼠。取肝组织行病理学检查。取血,使用全自动生化分析仪检测大鼠血清谷丙转氨酶（ALT）、谷草转氨酶 （AST）、总胆红素（TBIL）、总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）、空腹血糖（FBG）。结果 对照组和MCD组大鼠体质量分别为【（487.2±6.5）g和（155.8±3.1）g,P<0.05】,肝指数分别为【（2.92±0.06）%和（5.09±0.19）%,P<0.05】;MCD组大鼠肝组织出现明显的肝脏脂肪变、小叶炎症和气球样变,同时伴有轻度纤维化,茵栀黄处理组大鼠肝指数为（4.47±0.18）%,显著低于MCD组（P<0.05）;茵栀黄组和MCD组大鼠肝组织NAFLD活动度积分（NAS）分别为【（5.9±0.2）分和（7.2±0.1）分,P<0.05】,肝纤维化积分为【（0.3±0.2）分和（0.8±0.2）分,P<0.05】;茵栀黄组和MCD组大鼠血清ALT水平分别为【（68.4±6.4） U/L和（111.9±5.5） U/L,P<0.05】,AST分别为【（110.5±7.9） U/L和（170.5±10.8） U/L,P<0.05】,但是茵栀黄口服液灌胃对MCD大鼠血脂和血糖无显著影响。结论 茵栀黄口服液可以改善MCD诱导的NASH大鼠肝脏脂肪变、肝细胞气球样变、小叶炎症和纤维化,降低NASH大鼠血清转氨酶水平,为应用茵栀黄口服液处理NAFLD提供了实验依据。     

鼠尾草酸对肥胖性脂肪性肝炎大鼠血清生化指标和肝组织学变化的影响

目的探讨鼠尾草酸（CA）对肥胖性大鼠脂肪性肝炎的影响。方法 随机将28只SD大鼠分为对照组（n=8）和实验组（n=20）,分别喂以普通饲料和高脂饲料,10周后,将实验组大鼠随机分配到模型组（n=10）和CA组（n=10）,后者以cA200mg．kg^-1．d^-1体重灌胃,共6周。16周后,检测肝功能、血脂、胰岛素、SOD、MDA和脂肪细胞因子水平变化,并观察肝组织学变化。结果在16周末,对照组和模型组大鼠体重分别为449．5±47．4g对531．8±40．4g,内脏脂肪重为4．51±1．63g对6．37±1．66g,胰岛素抵抗指数（HOMA—IR）为0．30±0．15对0．65±0．34,ALT为36±18U／L对144±80U／L,AST为132±29U／L对218±64U／L,MDA为5．93±1．14mmol／ml对18．89±7．04mmol／ml,SOD为24．61±0．43U／ml对22．91±0．93U／ml,脂联素为3．58±0．70μg／ml对4．44±0．49μg／ml,瘦素为475．78±143．76pg／ml对651．86±185．92pg／ml,抵抗素为2．71±0．79ng／ml对5．23±2．67ng／ml（P〈0．01）;肝组织病理学检查显示模型组动物肝内呈重度脂肪变性;与模型组比,CA组大鼠上述各项指标均有不同程度的改善。结论CA对高脂饮食诱导的肥胖及脂肪性肝炎有很好的治疗效果。CA可能是抑制了内脏脂肪积聚,调节脂代谢,改善胰岛素抵抗,对抗氧化应激和脂质过氧化损伤。     

Anti-inflammatory and anti-oxidant effects of aloe vera in rats with non-alcoholic steatohepatitis

BACKGROUND Aloe vera exerts several biological activities, such as, anti-inflammatory, antioxidant, and antimicrobial effects. It was recently shown to reduce insulin resistance and triglyceride level. We hypothesized that aloe vera would have beneficial effects in alleviating non-alcoholic steatohepatitis(NASH) in rats.AIM To examine the therapeutic effects of aloe vera in NASH rats.METHODS All rats were randomly divided into 3 groups(n = 6 in each group). Rats in the control group were fed ad libitum with a standard diet for 8 wk. Rats in the NASH group were fed ad libitum with a high-fat high-fructose diet(HFHFD) for 8 wk. Rats in the aloe vera group were fed ad libitum with a HFHFD and aloe vera in dimethylsulfoxide(50 mg/kg) by gavage daily for 8 wk. Liver samples were collected at the end of the treatment period.RESULTS Hepatic malondialdehyde(MDA) levels increased significantly in the NASH group as compared with the control group(377 ± 77 nmol/mg vs 129 ± 51 nmol/mg protein, respectively, P 0.001). Glutathione(GSH) levels were significantly lower in the NASH group than the control group(9 ± 2 nmol/mg vs 24 ± 8 nmol/mg protein, respectively, P = 0.001). The expression of interleukin-18(IL-18), nuclear factor-kappa β, and caspase-3 increased, while peroxisome proliferator-activated receptor gamma decreased in the NASH group compared with the controls. Following aloe vera administration, MDA levels decreased(199 ± 35 nmol/mg protein) and GSH increased(18 ± 4 nmol/mg protein) markedly. Steatosis, hepatocyte ballooning, lobular inflammation and increased hepatocyte apoptosis were observed in the NASH group. Aloe vera treatment attenuated these changes in liver histology.CONCLUSION Aloe vera attenuated oxidative stress, hepatic inflammation and hepatocyte apoptosis, thus improving liver pathology in rats with NASH.     

水飞蓟素对非酒精性脂肪性肝炎大鼠小肠组织抗氧化作用的实验研究

目的探讨水飞蓟素对NASH大鼠小肠组织氧化应激损伤的影响。方法 50只Wistar大鼠被随机分为对照组、模型组和水飞蓟素干预组;对照组（10只）用普通饲料喂养,模型组（20只）通过高脂饮食建立NASH模型,水飞蓟素组（20只）给予高脂饮食加水飞蓟素灌胃,12周后评估。结果模型组较正常对照组大鼠血清TG、TC、ALT、AST水平明显升高（P〈0.01）,水飞蓟素组TG、TC、ALT、AST水平较模型组降低,差别有统计学意义（F=36.626～64.327,P〈0.01）;模型组大鼠较正常对照组小肠组织匀浆SOD活性明显降低（83.29±10.32U/mgprot对52.34±7.09U/mgprot）,MDA含量明显升高（0.56±0.07 Nmol/mgprot对0.97±0.09 Nmol/mgprot）,水飞蓟素组SOD活性较模型组有所升高,MDA水平下降,差异有统计学意义（F=23.488和10.609,P〈0.05）;内毒素水平为模型组（0.316±0.020EU/ml）〉水飞蓟素组（0.279±0.022EU/ml）〉正常对照组（0.234±0.021EU/ml）s;IgA水平为模型组〈水飞蓟素组〈正常对照组。结论抗氧化剂水飞蓟素不仅能提高肝脏本身的抗氧化能力,亦可以通过提高肠道抗氧化能力进而加强肠道的屏障作用。     

非酒精性脂肪性肝炎相关血清学指标的改变

非酒精性脂肪性肝炎(NASH)是一种慢性肝脏疾病,自上世纪八十年代以来逐渐被认识并引起重视。虽然关于NASH发病机制研究进展颇多,但NASH的血清学诊断指标缺乏特异性。此文从与肝损伤及NASH发病机制相关的四个方面,总结近年文献报道的NASH病变过程中血清学指标的改变,以期找到规律性的变化,为临床血清学诊断NASH提供参考。     

Preserved liver regeneration capacity after partial hepatectomy in rats with non-alcoholic steatohepatitis

AIM To evaluate the liver regeneration capacity(LRC) after partial hepatectomy(PH) in experimental non-alcoholic steatohepatitis(NASH).METHODS Fifty-four female rats were fed a high-fat, high-cholesterol diet(HFCD, 65% fat, 1% cholesterol) or standard diet(STD) for 16 wk. A 70% PH was performed and the animals were euthanised before PH or 2 or 5 d postPH. LRC was evaluated using: The total number of Ki-67 positive hepatocytes in the caudate lobe, N(Ki-67, lobe) evaluated in a stereology-based design, the regenerated protein ratio(RPR), prothrombin-proconvertin ratio(PP), and m RNA expression of genes related to regeneration.RESULTS The HFCD NASH model showed significant steatosis with ballooning and inflammation, while no fibrosis was present. Mortality was similar in HFCD and STD animals following PH. HFCD groups were compared to respective STD groups and HFCD animals had a significantly elevated alanine transaminase at baseline(P 0.001), as well as a significantly elevated bilirubin at day 2 after PH(P 0.05). HFCD animals had a higher N(Ki-67, lobe) at baseline,(P 0.0001), day 2 after PH(P = 0.06) and day 5 after PH(P 0.025). We found no significant difference in RPR or PP neither 2 or 5 d post-PH. Expression of liver regeneration genes(e.g., hepatic growth factor) was higher at both day 2 and 5 post-PH in HFCD groups(P 0.05).CONCLUSION NASH rats had a preserved LRC after hepatectomy when compared to STD rats. The methods and models of NASH are essential in understanding and evaluating LRC.     

Longitudinal correlations between MRE,MRI-PDFF,and liver histology in patients with non-alcoholic steatohepatitis: Analysis of data from a phase II trial of selonsertib

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CEUS and Fibroscan in non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

AIM: To determine intra-hepatic blood flow and liver stiffness in patients with non-alcoholic fatty liver disease(NAFLD) and non-alcoholic steatohepatitis (NASH) using contrast-enhanced ultrasound and fibroscan.METHODS: This prospective study included 15 patients with NAFLD, 17 patients with NASH and 16 healthy controls.In each patient, real-time ultrasound was used to locate the portal vein (PV) and the right liver lobe, and 5 mL of SonoVue? was then injected intravenous in a peripheral vein of the left arm over a 4-s span. Digital recording was performed for 3 min thereafter. The recording was subsequently retrieved to identify an area of interest in the PV area and in the right liver parenchyma(LP) to assess the blood flow by processing the data using dedicated software (Qontrast?, Bracco, Italy).The following parameters were evaluated: percentage of maximal contrast activity (Peak%), time to peak (TTP, s), regional blood volume (RBV, cm3), regional blood flow (RBF, cm3/s) and mean transit time (MTT, s).At 24-48 h post-injection, liver stiffness was evaluated using Fibroscan and measured in kPa. The statistical evaluation was performed using Student’s t test.RESULTS: In the PV, the Peak%, RBV and RBF were significantly reduced in the NAFLD and NASH patientscompared with the controls (Peak%: NAFLD 26.3 ± 6.6,NASH 28.1 ± 7.3 vs controls 55.8 ± 9.9, P 0.001;RBV: NAFLD 4202.3 ± 3519.7, NASH 3929.8 ± 1941.3vs controls 7473 ± 3281, P 0.01; RBF: NAFLD 32.5± 10.8, NASH 32.7 ± 12.1 vs controls 73.1 ± 13.9, P 0.001). The TTP in the PV was longer in both patient groups but reached statistical significance only in the NASH patients compared with the controls (NASH 79.5± 37.8 vs controls 43.2 ± 30, P 0.01). In the LP,the Peak%, RBV and RBF were significantly reduced in the NAFLD and NASH patients compared with the controls (Peak%: NAFLD 43.2 ± 7.3, NASH 41.7 ± 7.7 vs controls 56.6 ± 6.3, P 0.001; RBV: NAFLD 4851.5± 2009, NASH 5069.4 ± 2292.5 vs controls 6922.9 ±2461.5, P 0.05; RBF: NAFLD 55.7 ± 10.1, NASH 54.5 ± 12.1 vs controls 75.9 ± 10.5, P 0.001). The TTP was longer in both patient groups but did not reach statistical significance. The MTT in both the PV and LP in the NAFLD and NASH patients was not different from that in the controls. Liver stiffness was significantly increased relative to the controls only in the NASH patients(NASH: 6.4 ± 2.2 vs controls 4.6 ± 1.5, P 0.05).CONCLUSION: Blood flow derangement within the liver present not only in NASH but also in NAFLD suggests that a vascular flow alteration precedes liver fibrosis development.     

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.