三种大鼠脂肪肝模型的比较

目的比较胃造瘘法、酒精灌胃法制作酒精性肝病及高脂营养饮食复制非酒精性肝病的三种动物模型制作方法和优缺点,为酒精性肝病的研究奠定更有效的模型基础。方法分别从胃造瘘管内注入56%白酒,至每次18m1/kg·d,和经胃灌入同样白酒16～18ml/kg·d,早、晚各1次,制作胃造瘘和酒精灌胃大鼠模型;又给刚断乳SD雄性大鼠喂养自制营养高脂饲料,复制肥胖性脂肪肝模型。实验开始后4、8、12、24周,在各实验组中随机取8只大鼠,心包腔穿刺取血,测肝功及血糖、血脂:并取小块肝组织分作光镜和电镜观察。结果酒精灌胃组大鼠总体死亡率较高,达37.9%。胃造瘘组仅16.0%,两组相比差异非常显著,P<0.01。营养性肥胖模型组大鼠体重增长迅速,至12周时已达434.6±30.4g,24周时达502.16±16.4g,分别明显高于对照组的356.9±31.4g和433.1±36.9g,T=4.31,P<0.01。也明显高于另两组大鼠体重332.5±24.8g,412.5±34.4g和345.6±25.6g,430.6±26.9g,P<0.01。各模型组肝指数与相应之对照组比较,8周时始有显著差异,P<0.05;24周时差异更加显著,P<0.01。模型组血清肝功转氨酶较对照组显著升高,P<0.01;24周各模型组白蛋白明显下降,分别为28.04±2.42g/L,29.15±3.21g/L;28.56±193g/L,与对照组相比有显著差异,P均<0.05。肥胖模型组TCH、TG显著?

化痰方、肝脾方抗大鼠脂肪肝模型作用机制的比较研究

目的 :探讨和比较化痰方、肝脾方抗大鼠脂肪肝模型作用机制。方法 :用高脂饮食联合四环素腹腔注射致大鼠脂肪肝模型 ,观察肝组织病理变化 ,检测肝功能 (ALT、AST)、血甘油三酯 (TG)、肝匀浆TG、游离脂肪酸 (FFA)、丙二醛 (MDA)的含量。并与正常组、东宝肝泰组对照。结果 :三个用药组的血清ALT、AST及肝匀浆FFA、TG、MDA均显著低于模型组 (P <0 .0 1 ) ,并显示抗脂肪肝的作用强弱依次为 :肝脾组优于化痰组优于东宝组 (P <0 .0 5或P <0 .0 1 )。结论 :促进脂质代谢、抗脂质过氧化可能是化痰祛浊。

大鼠脂肪肝实验模型的建立

目的建立一个简便易行的脂肪肝动物模型。方法采用高脂饲料和CCl4皮下注射相结合,并以15%酒精水作为唯一饮料的方法复制大鼠脂肪肝模型。在光镜下观察形态学改变。结果3～5周后,模型组大鼠出现了程度不等的肝脂肪变性,肝细胞病理学总计分显著高于对照组(F=29.72,P<0.0001)。结论成功地建立了适用于防治人类脂肪肝研究的动物模型。

不同茶叶及茶多酚对高脂饲料致大鼠脂肪肝的影响

目的考察不同产地绿茶、红茶以及绿茶多酚对高脂饲料致大鼠脂肪肝的影响。方法大鼠喂饲高脂饲料制备大鼠脂肪肝模型,喂饲含不同茶叶或茶多酚的高脂饲料,观察体重变化、睾丸脂肪垫重量、血清TG和TC、肝脏脂肪性变、肝匀浆甘油三酯和胆固醇含量。结果各受试物组睾丸脂肪垫重量均较模型对照组减轻,云南绿茶组和四川绿茶组肝匀浆甘油三酯和胆固醇均明显低于模型对照;茶多酚组肝匀浆甘油三酯也明显低于模型对照组,但高于云南绿茶组和四川绿茶,茶多酚组肝匀浆胆固醇低于模型对照组,但明显高于云南绿茶组和四川绿茶组;云南红茶组肝匀浆甘油三酯和胆固醇与模型对照组相当。结论云南绿茶和四川绿茶均对高脂饲料致大鼠脂肪肝的形成有明显抑制作用;茶多酚也有一定作用;但云南红茶作用不明显。

调脂积颗粒对脂肪肝大鼠血脂及血液流变指标的影响

目的:探讨调脂积颗粒对脂肪肝大鼠血脂和血液流变性的影响。方法:采用复合方式建立大鼠脂肪肝模型,wastar大鼠48只随机分为四组,每组12只,即调脂积颗粒治疗组(调脂积组)、阳性对照组(易善复组)、正常组和模型组,测定四组生化指标及组织病理,同时检测全血高、中、低切黏度、血浆黏度。结果:调脂积颗粒可显著降低肝组织损伤和脂肪变性程度,降低肝组织及血清中甘油三酯、胆固醇含量,显著降低全血黏度及血浆黏度。结论:调脂积颗粒具有显著的抗肝组织损伤和脂肪变性作用,可明显降低脂肪肝大鼠血脂及改善血液流变性,对脂肪肝有治疗作用。

肝脂片对非酒精性脂肪肝肝细胞色素P4502E1表达及与氧化抗氧化关系的影响

目的 研究肝脂片对非酒精性脂肪肝肝细胞色素P4502E1表达及与氧化抗氧化关系的影响。方法 将50只雄性Wistar大鼠随机分为5组，即正常对照组、高脂模型组、东宝肝泰组（0．7g／kg）、肝脂片高、低剂量组（2g、1g生药／kg）。除正常对照组外，其余4组均喂食高脂饲料复制大鼠脂肪肝模型，于此同时，各给药组按实验设计给予药物，正常对照组和模型组以等量蒸馏水灌胃。12周后，观察肝组织病理形态的变化和肝细胞色素P4502E1的表达；

Signal transduction mechanism of TRB3 in rats with non-alcoholic fatty liver disease

AIM： To evaluate the possible role of Tribble 3 （TRB3） in a rat model of non-alcoholic fatty liver disease （NAFLD） and its signal transduction mechanism.METHODS： Thirty Sprague-Dawley rats were randomized into three groups： normal control group, non-alcoholic fatty liver group A （fed on a high-fat diet for 8 wk） and group B （fed on a high-fat diet for 16 wk）. To determine the degree of hepatic steatosis in rats of each group, livers were stained with hematoxylin and eosin, and evaluated; real-time fluorescent quantitative reverse transcriptase-polymerase chain reaction was performed to measure the expression levels of TRI33 mRNA, and Western blotting analysis was done to determine the expression levels of protein kinase B （Akt） and phosphorylated protein kinase B （p-Akt-Thr308, p-Akt-Ser473）.RESULTS： Hepatic steatosis was evident in both NAFLD groups： mild to moderate hepatic steatosis occurred in group A, mainly as mild steatosis.Moderate to severe hepatic steatosis occurred in group B, mainly as severe steatosis. The expression level of TRB3 mRNA in group B was significantly higher than in the control group （122.28 ± 95.37 vs 3.06 ± 2.33,P = 0.002） and group A （122.28 ± 95.37 vs 5.77 ± 4.20,P = 0.001）. There was no significant difference in the expression levels of Akt （1.03 ± 0.53 vs 1.12 ± 0.77,P = 0.729） and p-Akt-Thr308 （0.82 ± 0.45 vs 0.92 ± 0.38, P = 0.592） between group A and the control group. The expression level of Akt and p-Akt-Thr308 in group B was significantly lower than in group A （Akt 0.41 ± 0.16 vs 1.12 ± 0.77, P = 0.008; p-Akt-Thr308 0.47 ± 0.19 vs 0.82 ± 0.45, P = 0.036） and the control group （Akt 0.41 ± 0.16 vs 1.03 ± 0.53, P = 0.018;p-Akt-Thr308 0.47 ± 0.19 vs 0.92 ± 0.38, P = 0.010）.The expression level of p-Akt-Ser473 in group A was significantly higher than in group B （1.48 ± 0.50 vs 0.81± 0.39, P = 0.041） as well as the control group （1.48 ± 0.50 vs 0.45 ± 0.26, P = 0.003）.CONCLUSION： TRB3 blocks insulin signaling by inhibiting Akt activation, which contributes to insulin resistance. It may be an important factor in the occurrence and development of NAFLD.

Effects of Yinchenhao Decoction(茵陈蒿汤) for Non-alcoholic Steatohepatitis in Rats and Study of the Mechanism

Objective:To observe the effects of Yinchenhao Decoction(茵陈蒿汤) for non-alcoholic steatohepatitis(NASH) in rats and study the mechanism.Methods:Total 18 male SD rats were randomly divided into a normal control group,a model group and a treatment group,6 rats in each group.Rats in the model and treatment groups were fed with high-fat forage for 10 weeks to prepare the NASH model,and the rats in the treatment group were administrated with Yinchenhao Decoction from the 6th week for 5 weeks.All rats were sacrificed at the end of the10th week and the samples were collected.Serum alanine aminotransferase(ALT) activity,tumor necrosis factor-α(TNF-α) level,and hepatic triglyceride(TG) and free fatty acid(FFA) contents were determined.Hepatic pathological changes were detected by HE staining.Results:Serum ALT activity,TNF-α level,hepatic TG and FFA contents,and the fatty deposition in hepatocytes were significantly reduced in the rats of the treatment group.Conclusion:Yinchenhao Decoction has good therapeutic effects for NASH,protecting the liver function and reducing the fatty deposition in liver,which are possibly related with reduction of FFA content and inhibition of TNF-α expression.

Study on effects of Zhi Zi(Fructus gardeniae) on non-alcoholic fatty liver disease in the rat

OBJECTIVE:To investigate the effects of Zhi Zi(Fructus Gardeniae) on non-alcoholic fatty liver disease(NAFLD) induced by a high-fat diet in the rat.METHODS:A rat model of NAFLD was established using a high-fat diet.Twenty one rats were randomly divided into a normal group,a model group and a Zhi Zi treatment group,7 rats per group.Drinking water and the drug were intragastrically administrated for 5 weeks.Samples were then taken to observe pathological changes of the liver tissue(HE staining);changes in the fat metabolism pathway e.g.triglyceride(TG) and free fatty acid(FFA) content;alterations in liver function,i.e.serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) activity;and differences in tumor necrosis factor α(TNF-α) and P-IkB protein expression in the liver tissue.RESULTS:Fatty degeneration and vacuole-like changes of different degrees occurred in hepatic cells of the model group.Markers for fat metabolism,serum ALT and AST activities,and expressionof TNF-α and P-IkB proteins in liver tissue significantly increased.Fat metabolism in the Zhi Zi group significantly reduced,as shown by a drop in marker levels.Serum ALT and AST activities,and expression of TNF-α,P-IkB proteins in liver tissue were also significantly decreased in this group.CONCLUSION:Zhi Zi has a very strong inhibitory action on lipidosis and inflammatory injury in the rat model of NAFLD.This mechanism may possibly be related to the inhibition of the free fatty acid metabolism pathway.