海狗油ω-3多不饱和脂肪酸对大鼠脂肪肝的治疗作用

目的观察海狗油ω 3多不饱和脂肪酸 (海狗油 )对大鼠脂肪肝的治疗作用。方法小剂量四氯化碳合并高脂饲料复制大鼠脂肪肝模型 7周后 ,模型组ig等体积橄榄油 ,阳性药组ig辛伐他汀 4mg/kg ,海狗油低、中、高剂量组分别ig海狗油 0 .5、1.6、4 .8g/kg ,1次 /d ,连续 8周 ,正常大鼠作为空白组。以肝脏的重量、肝脂质含量、6 酮 前列腺素F1α与血栓素B2 比值 (6 keto PGF1α/TXB2 )、脂质过氧化作用和病理检查为主要衡量指标 ,观察其防治效果。结果海狗油各组与模型组相比大鼠肝重减轻 ,肝组织中甘油三脂、总胆固醇、丙二醛、游离脂肪酸含量显著降低 ,超氧化物歧化酶活性升高 ,6 keto PGF1α/TXB2 增加 ,病理检查苏丹Ⅲ染色、HE染色和细胞色素P4 5 0 2E1免疫组织化学染色显示肝内脂变减轻 ,表达减弱。结论海狗油对实验性脂肪肝的形成具有治疗作用。

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?

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。

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。

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。

鸡骨草防治大鼠脂肪肝的实验研究

目的:探讨鸡骨草对脂肪肝大鼠血脂代谢及其肝脏病理、肝窦内皮细胞窗孔形态学的影响。方法:将SD大鼠随机分为正常对照组、模型组、辛伐他汀组(7.2 mg/kg)、绞股蓝组(16.2 mg/kg)及鸡骨草高、中、低剂量组(40、20、10 g/kg),高脂饲料喂养3 w建立脂肪肝模型后,各药物组给予药物灌胃3 w并继续给予高脂饲料。第43天采血测转氨酶和血脂四项,并取肝组织作病理切片,光镜下观察肝组织,或在体灌注后取肝组织固定,经处理后在扫描电镜下观察肝窦窗孔变化。结果:鸡骨草高剂量能降低高脂模型大鼠血清中AST、ALT、TC、TG、LDL-C并升高HDL-C含量,在光镜和扫描电镜下亦观察到其肝组织形态以及LSEC窗孔恢复趋向正常,中剂量作用稍弱,低剂量效果不明显。结论:鸡骨草可调节高脂模型大鼠血脂水平,并改善肝脏组织的病理变化,具有降脂、保肝作用,能在一定程度上防治脂肪肝。

健脾活血化痰法对脂肪肝大鼠血脂及肝功能的影响

目的:探讨健脾活血化痰法治疗脂肪肝的意义及药理作用。方法:采用高脂饮食诱导大鼠脂肪肝模型,实验分为4组:空白对照组,模型对照组,标准对照组(易善复胶囊+阿托伐他汀)和中药试验组。结果:表明健脾活血化痰方对血清胆固醇(TC)、低密度脂蛋白(LDL)有明显降低作用,能提高血清高密度脂蛋白(HDL)的含量,对甘油三酯(TC)影响不显著;肝功能方面,健脾活血化痰方对降低血清中谷丙转氨酶(ALT)与对照组结果有相近意义,对降低谷草转氨酶(AST)明显优于对照组。肝组织切片试验组脂滴明显堆积,较各对照组肝组织切片显示,脂滴堆积明显减轻。结论:健脾活血化痰法对于脂肪肝大鼠具有较好降脂及保肝的作用。

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。

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。

羟基红花黄色素A对高脂血症脂肪肝大鼠肝脏功能的干预作用

目的研究羟基红花黄色素A对高脂血症脂肪肝大鼠肝脏功能的干预效果。方法以喂饲法建立高脂血症脂肪肝大鼠模型,实验分为正常对照组、高脂血症脂肪肝组与羟基红花黄色素A高、中、低剂量(2、4、8mg/kg)干预组、阿托伐他汀钙片阳性对照组。正常对照组和高脂血症脂肪肝组给予生理盐水灌胃,每天1次,连续2周后,测定肝脏中谷草转氨酶、谷丙转氨酶、超氧化物歧化酶、丙二醛、过氧化氢酶,并H&E染色及油红O染色观察其肝脏结构变化及脂肪变程度,western blot法测定肝脏功能相关蛋白。结果与正常对照组相比,高脂血症脂肪肝大鼠肝脏中丙氨酸氨基转移酶、天冬氨酸转氨酶生化指标异常升高,同时超氧化物歧化酶、过氧化氢酶水平降低,且肝脏发生脂质沉积异常形态变化。羟基红花黄色素A各剂量组均能显著改善高脂血症脂肪肝大鼠的肝脏异常形态变化,机制与升高高脂血症下异常降低的SREBP-2、LDL-R、HMGCR、FAS蛋白相关。结论羟基红花黄色素A可有效干预高脂血症脂肪肝大鼠肝脏血脂水平,对肝脏脂肪变性程度及相关脂质指标有所改善。

金芪降糖胶囊对高脂血症脂肪肝大鼠降脂保肝作用研究

目的:建立高脂血症脂肪肝大鼠模型,研究金芪降糖胶囊对非酒精性脂肪肝大鼠降脂保肝作用的影响。方法:Wistar大鼠饲腹腔注射维生素D3注射液60万U·kg-1,同时给予高脂饲料喂养,建立高脂血症脂肪肝大鼠模型,连续给药12周,检测血清中甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白(HDL-c)、低密度脂蛋白(LDL-c)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、丙二醛(MDA)、超氧化物歧化酶(SOD)。结果:金芪降糖胶囊各剂量组及阳性对照组大鼠TC、TG和LDL-c与模型组相比均显著性降低(P<0.05,P<0.01),金芪降糖胶囊各剂量组组HDL-c与模型组比较显著升高(P<0.05);金芪降糖胶囊能有效的抑制肝损伤导致的血清酶ALT、AST、MDA水平的升高,同时提高血清酶SOD活力,与模型组比有差异(P<0.05,P<0.01)。结论:金芪降糖胶囊可有效改善高脂血症脂肪肝大鼠糖脂代谢异常,并对肝损伤有明显的抑制作用。

参芪肝康颗粒对非酒精性脂肪肝大鼠丙二醛、超氧化物歧化酶的影响

目的:探讨参芪肝康颗粒对非酒精性脂肪肝大鼠脂质过氧化物(LPO)的降解产物丙二醛(MDA)和超氧化物歧化酶(SOD)的影响。方法:通过高脂饮食来建立大鼠非酒精性脂肪肝模型,在造模成功以后给予"参芪肝康颗粒",干预3周后进行各组大鼠血清和肝匀浆MDA、SOD的含量变化的检测。结果:模型组大鼠血清和肝匀浆中MDA含量明显高于正常组,SOD水平明显低于正常组;在给药治疗以后,参芪肝康颗粒各组与模型组相比,血清及肝匀浆中MDA含量显著降低,SOD水平均明显增高;和阳性对照组相比,大鼠肝匀浆MDA含量降低及SOD含量升高以参芪肝康颗粒预防组和高剂量组最为显著。结论:参芪肝康颗粒提高血清和肝组织的抗氧化能力显著,能够明显抵御肝细胞的过氧化和氧应激,避免损伤肝细胞,以达到预防和治疗非酒精性脂肪肝的目的。

理气化痰祛瘀中药复方对非酒精性脂肪肝大鼠肝组织NF-κB、IκBα表达的影响

目的:观察理气化痰祛瘀中药复方对高脂饮食诱导的非酒精性脂肪肝大鼠肝组织NF-κB、IκB表达的影响。方法:以高脂饲料喂养大鼠造模。造模结束后,分别以不同剂量的理气化痰祛瘀中药和易善复灌胃治疗,模型组和正常组予等容量的蒸馏水灌胃,均连续8周。取肝组织HE染色观察大鼠肝脏脂肪变程度,免疫组化法检测肝组织中NF-κBp65、IκBα的表达。结果:模型组大鼠肝组织脂肪变程度较正常组明显升高(P<0.01);应用大、中、小剂量中药治疗后肝组织脂肪变程度较模型组明显下降(P<0.01)。模型组大鼠肝组织中NF-κBp65、IκBα的阳性表达明显高于正常组(P<0.01);应用大、中、小剂量中药治疗后大鼠肝组织中NF-κBp65表达较模型组明显降低(P<0.05)。结论:理气化痰祛瘀中药能明显改善高脂饮食诱导的大鼠肝组织脂肪变性,抑制大鼠肝组织NF-κBp65表达可能是其作用机制之一。

降脂分散片对大鼠高脂血症性脂肪肝的影响

[目的]观察降脂分散片对大鼠高脂血症性脂肪肝的影响。[方法]将60只wistar大鼠按称重顺序编原始号,查随机数字表随机分为空白对照组、模型对照组、降脂分散片组(低0.22g/kg、中0.66g/kg、高1.32g/kg剂量组),脂必妥阳性药物对照组。每组10只,雌雄各半,分笼饲养,每笼5只。空白对照组、模型对照组灌胃蒸馏水,给药组灌胃相应药物;空白对照组喂饲普通饲料,其余各组喂饲高脂饲料造大鼠脂肪肝模型,给药第8周检测血清总胆固醇(TC)、甘油三酯(TG)、丙氨酸转氨酶(ALT)、谷草转氨酶(AST)以及肝组织中的游离脂肪酸(FFA)、丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)。[结果]降脂分散片呈剂量依赖性:显著降低脂肪肝模型大鼠血清TC、TG、ALT、AST以及肝脏FFA、MDA含量(P<0.01),显著提高脂肪肝模型大鼠肝脏SOD、GSH-Px的活性(P<0.01)。[结论]降脂分散片对大鼠高脂血症性脂肪肝影响呈量效关系,可抑制肝脏脂肪变,减轻肝内脂质代谢紊乱对肝细胞的损伤,提高肝组织抗氧化能力。

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；

补肾化浊方对非酒精性脂肪肝大鼠血清瘦素与胰岛素抵抗的影响

目的:研究补肾化浊方对高脂饲料喂养大鼠肝功、血脂、血糖、胰岛素抵抗、瘦素的影响,探讨补肾化浊方防治非酒精性脂肪肝作用机制。方法:45只Wistar大鼠随机分为空白组、模型组、水林佳(19 g.kg-1)组和补肾化浊方(含生药20 g.kg-1)组。空白组予普通饲料喂养,其余3组予高脂饲料喂养,水林佳组、补肾化浊方组在高脂饲料喂养的同时进行相应的药物干预,12周后,处死大鼠,计算大鼠肝指数、Lee’s指数、胰岛素抵抗指数(IRI)、胰岛素敏感指数(ISI),检查肝功能、血脂、血糖、胰岛素(INS)、瘦素(LEP),并进行肝脏病理检查。结果:与模型组比较,补肾化浊方组、水林佳组均能明显改善大鼠丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、LEP水平(P<0.01);在改善大鼠INS,IRI,ISI方面,补肾化浊方组优于水林佳组(P<0.05或P<0.01),水林佳组对INS,IRI无明显改善作用,水林佳组、补肾化浊方组大鼠脂肪染色、糖原染色改善优于模型组(P<0.05或P<0.01)。结论:补肾化浊方通过保肝、调节血脂、改善瘦素及胰岛素抵抗等方面发挥治疗作用。

Effects of emodin on treating murine nonalcoholic fatty liver induced by high caloric laboratory chaw

AIM: To investigate the effects of emodin on the treatment of non-alcoholic fatty liver in rats induced by high caloric laboratory chaw. METHODS: Non-alcoholic fatty liver model was successfully established by feeding with high caloric laboratory chaw for 12 wk. Then the model rats were randomly divided into 3 groups, namely model control group, emodin group and dietary treatment group. The rats in emodin group were given emodin at dose of 40 mg/(kg·d) while animals in other groups were given distilled water of the same volume. The rats in model control group were fed with high caloric laboratory chaw while animals in other groups were fed with normal diet. Four weeks later, liver index (liver/body weight ratio), serum activities of liver-associated enzymes, blood lipid, fasting blood glucose, fasting plasma insulin, HOMA insulin resistance index (HOMA-IR), hepatic triglyceride content and histology features of all groups were assayed. The expression of hepatic peroxisomal proliferator activated receptor (PPAR) gamma was determined by RT-PCR. RESULTS: The body weight, liver index, serum activities of alanine aminotransferase (ALT), blood lipid, hepatic triglyceride content of model control group were significantly elevated, with moderate to severe hepatocyte steatosis. The expression of hepatic PPAR gamma mRNA was obviously reduced in model control group. Compared with model control group, the body weight, liver index, serum activities of ALT, blood lipids and hepatic triglyceride of emodin group significantly decreased and hepatic histology display was also greatly improved. Meanwhile, the expression of hepatic PPAR gamma mRNA was elevated. However, high serum activities of ALT and hyperlipidemia were persisted in dietary treatment group although liver index was decreased and liver histology was somewhat improved. CONCLUSION: It is suggested that emodin might be effective in the treatment of non-alcoholic fatty liver in rats. Its therapeutic mechanism could be associated with increasing the expression of hepatic PPAR gamma mRNA.

Increased intestinal permeability in pathogenesis and progress of nonalcoholic steatohepatitis in rats

AIM： To investigate whether increased intestinal permeability contributes to the pathogenesis and progress of nonalcoholic steatohepatitis by observing its dynamic change in rat models. METHODS： Rat models of nonalcoholic steatohepatitis were established by giving a fat-rich diet. The rats were sacrificed at wk 8, 12 and 16 during the study. Rats fed with normal diet were taken as control. Plasma D-lactate, plasma diarnine oxidase, serum lipids and liver transarninases were measured in blood of the femoral artery. Hepatic steatosis and inflammation were assessed by haematoxylin-eosin staining. RESULTS： A rat model of nonalcoholic steatohepatitis was established successfully. Plasma D-lactate level in model group at wk 8, 12 and 16 and diarnine oxidase level in model group at wk 12, 16 increased significantly compared with those in control group. There were notable differences of D-lactate and diarnine oxidase level in model group between wk 8 and 12 as well as between wk 12 and 16. Serum lipids, liver transaminases and liver injury also increased with disease development CONCLUSION： Increased intestinal permeability caused by intestinal bacterial overgrowth and endotoxin-induced intestinal destruction exists in rats with nonalcoholic steatohepatitis, which may partially explain the pathogenesis and progress of this disease.

Hepatic steatosis prevents heme oxygenase-1 induction by isoflurane in the rat liver

AIM:To characterize the inductive effects of isoflurane(ISO) on hepatic heme oxygenase-1(HO-1) in an animal model of hepatic steatosis.METHODS:Lean(LEAN) and obese(FAT) Zucker rats were randomized into 4 groups:1:LEAN + pentobarbital sodium(PEN);2:LEAN + ISO;3:FAT + PEN;4:FAT + ISO.The animals were mechanically ventilated for 6 h.In vitro analyses of liver tissue included determination of HO-1 mRNA and protein expression as well as measurement of HO enzyme activity and immunohistochemical analyses.RESULTS:Compared to PEN treatment,ISO administration profoundly induced hepatic HO-1 mRNA and protein expression and significantly increased HO enzyme activity in lean Zucker rats.In contrast,no difference in HO-1 gene expression was observed after ISO or PEN anesthesia in obese Zucker rats.CONCLUSION:The present study demonstrates that ISO is an inducer of hepatic HO-1 gene expression in non-steatotic organs but failed to upregulate HO-1 in steatotic livers.

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.