维生素E和硒对肝星状细胞中金属蛋白酶1组织抑制剂mRNA表达的影响

目的:研究维生素E(Vit E)和不同剂量硒(Se)对肝纤维化大鼠肝星状细胞(HSC)中金属蛋白酶1组织抑制剂(TIMP-1)mRNA表达的影响,从分子水平揭示Vit E和Se对肝纤维化的治疗作用及其机制.方法:用40%CCL4制备大鼠肝纤维化模型,并在饲料中补充Vit E和不同剂量的Se进行营养干预.应用HE常规染色和Masson三色胶原染色对肝组织切片行组织病理学检查;应用逆转录聚合酶链反应(RT-PCR)技术,以β肌动蛋白(actin)作为内对照,检测HSC中TIMP-1 mRNA表达的变化.结果:Vit E补充组(250 mg/kg食物)和低Se补充组(0.2 mg/kg食物)大鼠与病理造模组相比,肝纤维化程度显著减轻,HSC中TIMP-1 mRNA的表达显著降低(P＜0.05);而较高剂量Se(1.0mg/kg食物)则使HSC中TIMP-1 mRNA的表达呈上升趋势(与病理造模组相比,P＞0.05).结论:Vit E和适当剂量的Se能显著减轻大鼠肝纤维化程度,下调HSC中TIMP-1 mRNA的表达;而过高剂量的Se则无上述作用.     

亚硒酸钠对糖尿病小鼠肝生化功能的影响及大蒜素的防护作用

目的：观察亚硒酸钠对糖尿病小鼠肝功能、肝抗氧化功能的影响及大蒜素的防护作用。方法：采用四氧嘧啶复制小鼠糖尿病模型，检测正常组、造模组、亚硒酸钠组、大蒜素组的肝功能和肝脏抗氧化功能的指标。结果：空腹血糖大于２００ｍｇ／ｄｌ的糖尿病小鼠３周内肝脏谷丙转氨酶（ＧＰＴ）、谷草转氨酶（ＧＯＴ）活性无明显改变：肝糖元含量有所下降，肝线粒体脂质过氧化产物ＭＤＡ含量明显升高，超氧化物歧化酶（ＳＯＤ）活性明显降低，     

虎眼万年青对四氯化碳致大鼠急性肝损伤防治作用的实验研究

目的研究虎眼万年青对大鼠急性肝损伤的防治作用。方法将实验大鼠随机分为正常对照组、四氯化碳（CCl4）急性肝损伤组、甘草酸二胺防治组和虎眼万年青防治组。观察各组大鼠肝功能和肝组织的变化。结果造模2周后，急性肝损伤组大鼠血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、前白蛋白（PA）分别为1012．5±443．74U／L、955．10±436．89U／L、14．7±2．58mg／L，虎眼万年青防治组分别为359．70±385．04U／L、451．50±297．84U／L、26．2±4．21mg／L，说明虎眼万年青能显著降低急性肝损伤大鼠血清ALT、AST的活性（P〈0．05），提高大鼠血清PA水平（P〈0．05），并改善肝组织炎性反应，作用与甘草酸二胺防治组无显著性差异（P〉0．05）。结论虎眼万年青对四氯化碳致大鼠急性肝损伤有明显的防治作用。     

黄芪总黄酮对二甲基亚硝胺诱导的大鼠肝硬化的干预作用

[目的]研究黄芪总黄酮（TFA）对二甲基亚硝胺（DMN）诱导的大鼠肝硬化的干预作用.[方法]雄性SD大鼠53只,随机分为正常组（10只）和造模组（43只）,造模组给予DMN腹腔注射造模4周.实验第3周造模组大鼠随机分为模型组（14只）和TFA干预低剂量组（15 mg/kg,14只）、高剂量组（30 mg/kg,15只）,干预组予TFA灌胃共4周.正常组和模型组予等量蒸馏水灌胃.实验结束后处死大鼠,采集血和肝组织,分别检测血清生化学指标、肝组织羟脯氨酸（Hyp）含量和肝组织病理学观察.[结果]与模型组相比,TFA干预组大鼠肝/体比均显著升高（P＜0.01）,脾/体比均显著下降（P＜0.01）,血清丙氨酸氨基转移酶、天冬氨酸转氨酶、总胆红素及γ-谷酰氨转移酶均显著下降（P＜0.05）,白蛋白水平显著升高（P＜0.05）;且高剂量组上述指标改善程度优于低剂量组（P＜0.05）.与模型组相比,TFA低剂量组和高剂量组Hyp均显著降低（P＜0.01）,高剂量组改善程度优于低剂量组（P＜0.05）.苏木精-伊红染色显示TFA干预组肝组织肝窦狭窄、汇管区扩张、假小叶形成以及肝细胞炎症出血、变性坏死的程度均有所减轻,尤以高剂量组改善明显.[结论]TFA对DMN诱导的大鼠肝硬化有良好的干预作用.     

不同硒水平饲料对大鼠抗氧化和肝纤维化的影响

目的　旨在研究不同剂量硒对大鼠抗氧化和肝纤维化的影响。方法　采用ＣＣｌ４ 诱导大鼠肝纤维化模型。同时补充高硒（１．０ｍｇ／ｋｇ ｄｉｅｔ）和低硒（０．２ｍｇ／ｋｇ） 予以防治,观察不同剂量硒对大鼠抗氧化及肝纤维化各项指标的影响。结果　补充低剂量硒（０ ．２ｍｇ／ｋｇ ｄｉｅｔ） 能显著降低大鼠血清谷丙转氨酶（ＡＬＴ） 、Ⅲ型前胶原（ＰＣⅢ） 血清和肝组织中脂质过氧化物丙二醛（ＭＤＡ） ;显著提高谷胱甘肽过氧化物酶（ＧＰＸ） 和超氧化物歧化酶（ＳＯＤ） 活性;并能显著减轻肝脏胶原纤维增生程度。但补充过高硒剂量时（１ｍｇ／ｋｇ ｄｉｅｔ）,则无上述作用。结论　硒对机体有双重影响,适当剂量硒增强机体抗氧化功能和抗肝纤维化作用;过高剂量硒会使机体中毒。     

骨髓干细胞移植治疗急性肝损伤大鼠的实验研究

目的评价骨髓干细胞移植治疗急性肝损伤大鼠的治疗作用。方法采用2-乙酰氨基芴造成急性化学性肝损伤及2/3肝脏切除造成急性物理性肝损伤两种大鼠肝损伤模型,观察门静脉和肝实质内两种移植方式移植骨髓干细胞对以上两种急性肝损伤大鼠的治疗作用。结果在化学性肝损伤大鼠,细胞移植后3周,肝内注射组血清白蛋白明显高于门静脉移植组(P=0.03);在物理性肝损伤大鼠,移植后48h,门静脉移植组和肝内注射组血清谷丙转氨酶均明显升高,且肝内注射组明显高于门静脉移植组(P=0.0009),而谷草转氨酶和血清白蛋白均无明显异常(P0.05);移植后3周,两组各项肝功指标均无明显异常。结论骨髓干细胞移植可以促进化学性肝损伤大鼠血清白蛋白恢复,肝内注射方式较门静脉移植疗效更好,肝实质内移植骨髓干细胞易引起谷丙转氨酶升高。     

亚硝酸钠致大鼠心肌谷胱甘肽过氧化物酶和硒含量的变化及维生素E和硒对其酶活性的影响

大白鼠喂饲低硒富锰基础饲料，并分别向基础饲料中添加维生素E和栖，观察在亚硝酸钠急性中毒情况下各组大鼠心肌谷胱甘肽过氧化物酶（GSH－Px）、心肌硒元素含量及血清中维生素E（VtE）的变化。结果表明，亚硝酸钠可使低硒富锰所致大鼠心肌谷胱甘肽过氧化物酶活性明显下降，VtE和硒则可保护此酶活性防止其下降，提示除低硒富锰外，亚硝酸盐过多可能参与克山病发病环节。     

饮食补充Vit E防止四氯化碳引起的慢性肝损害和肝硬化

以往本实验室研究表明对实验动物应用Vit E可防止其急性CCl_4性肝坏死,本文研究给大鼠饮食补充Vit E后是否影响CCl_4引起的慢性肝损害和肝硬化。材料和方法:将最初体重为40～50 g的雄性幼年Wistar大鼠分两组饲养,Ⅰ组用标准饲料(含Vit E50mg/kg),Ⅱ组在标准饲料中加用Vit E(Vit E总量250mg/kg)。饲养3周后分别从两组中选体重为130～140g大鼠的腹腔内注射CCl_4 0.15ml,每周3次,计5周以上。Ⅰ组为对照组(n=10),Ⅱ组为饮食补充Vit E组(n=10),Ⅲ组为标准饲料加CCl_4组(n=12),Ⅳ组为     

黄芪与三七有效成分配伍对动脉粥样硬化大鼠模型TIMP-1表达的影响

目的利用高脂饲料诱发动脉粥样硬化（AS）大鼠模型，观察益气活血代表中药黄芪、三七有效成分黄芪槲皮素（Que）和三七总皂甙（tPNS）抗AS的作用，探讨二者单独使用及不同比例组方对AS大鼠模型血清基质金属蛋白酶特异性抑制物（TIMP-1）表达的影响。方法将64只雄性健康Wistar大鼠随机分为正常组和造模组，正常组10只喂养普通饲料，造模组54只喂养高脂饲料。造模成功后，造模组大鼠停喂高脂饲料改为普通饲料喂养，剩余48只造模组大鼠再随机分为6组，用不同药物干预灌胃30d后，取各组大鼠血清用酶联免疫吸附试验（ELISA）测血清TIMP-1的表达。结果Que、tPNS单用以及2：1组方、3：1组方皆可增加TIMP-1表达，以3：1组方为最优组。结论Que、tPNS单用及2：1、3：1组方皆可增加TIMP-1表达，联合用药比单独应用抗AS效果好，并在一定范围内随著益气药物剂量增加，抗AS作用增强。这可能是益气活血法抗AS作用机制之一。     

脂欣康胶囊对高脂血症大鼠血脂的影响及其抗氧化作用

目的观察脂欣康胶囊对实验性高脂血症大鼠血脂的影响及其抗氧化作用。方法45只大鼠喂饲高脂饲料造成高脂血症模型后,随机分为脂欣康胶囊治疗组、金甲益心酮对照组和高脂血症造模组各15只,检测3组血脂和抗氧化指标变化。结果高脂饲料饲养6周后,3组血清TC、TG明显升高,HDL-C明显降低,提示造模成功;治疗组、对照组给药6、15周后,血清TC、TG降低,HDL—C升高,治疗组血脂指标改善优于对照组（P均〈0．05）。15周后,治疗组、对照组血清NO和超氧化物歧化酶（SOD）活力升高,血清氧化型低密度脂蛋白（OX-LDL）降低,治疗组抗氧化指标优于对照组（P均〈0．05）。结论脂欣康胶囊有明显降低血脂、抗氧化和调节血管活性物质的作用;其机制可能与调节脂类代谢、清除自由基和抑制脂质过氧化等作用有关。     

Effects of dietary supplementation with vitamin E and selenium on rat hepatic stellate cell apoptosis

AIM: To evaluate the effects of dietary supplementation with vitamin E and selenium on proliferation and apoptosis of hepatic stellate cells (HSCs), in acute liver injury induced by CCl4, and to explore their role in the recovery from hepatic fibrosis phase. METHODS: An acute liver damage model of rats was established by intraperitoneal injection of carbon tetrachloride (0.3 mL/100 g body weight) twice a week, then the rats were killed at 6, 24, 48, and 72 h after the first and third injection, respectively. A liver fibrosis model was established by the same injection for 8 wk. Then three rats were killed at 3, 7,14, and 28 d after the last injection, respectively. The rats from the intervention group were fed with chow supplemented with vitamin E (250 mg/kg) and selenium (0.2 mg/kg), and the rats in the normal control group and pathological group were given standard chow. Livers were harvested and stained with hematoxylin and eosin, Sirius red. Activated HSCs were determined by α-smooth muscle actin immunohistochemistry staining. Apoptotic HSCs were determined by dual staining with the terminal deoxynucleotidyl transferase UTP nick end labeling (TUNEL) and α-smooth muscle actin immunohistochemistry. Serum alanine aminotransferase and aspartate aminotransferase were also analyzed. RESULTS: In the acute liver damage model, the degree of liver injury was more serious in the pathological group than in the intervention group. At each time point, the number of activated HSCs was less in the intervention group than in the pathological group, while the number of apoptotic HSCs was more in the intervention group than in the pathological group. In the liver fibrosis model, the degree of liver fibrosis was more serious in the pathological group than in the intervention group. At each time point, the number of activated HSCs was less in the intervention group than in the pathological group, and the number of apoptotic HSCs was more in the intervention group than in the pathological group. CONCLUSION: Vitamin E and selenium supplementation at the given level can inhibit CCl4-induced activation and proliferation of HSCs and promote the apoptosis of activated HSCs in acute damage phase. Vitamin E and selenium can also effectively decrease the degree of hepatic fibrosis and promote the recovery process.     

褪黑素、维生素C在重症急性胰腺炎脂质过氧化反应中的作用

目的观察褪黑素(MLT)、维生素C(VitC)在实验性急性坏死性胰腺炎(ANP)时对脂质过氧化反应的影响。方法100只Wistar大鼠随机分为正常对照组(正常组)、ANP 生理盐水组(ANP组)、ANP MLT组(MLT组)、ANP VitC组(VitC组)、ANP MLT VitC组(联合组)。采用胰胆管末端穿刺逆行注入3%牛磺胆酸钠(1ml/kg体重)制备ANP模型。MLT组于制模后即刻皮下注射MLT50mg/kg体重,VitC组肌内注射VitC1g/kg体重。联合组则合并应用。术后6h和24h处死大鼠,取血检测血清淀粉酶(AMY)、血清丙二醛(MDA)和超氧化物歧化酶(SOD)活性。胰腺病变程度按病理学评分,电镜观察超微结构。结果MLT组、VitC组和联合组在各时间点的AMY及MDA含量较ANP组显著降低(P<0.01),各时间点的SOD活性较ANP组显著升高(P<0.01)。MLT组、VitC组和联合组各时间点的胰腺炎症、腺泡坏死程度及出血均较ANP组明显减轻,病理分值明显低于ANP组(P<0.01或P<0.05)。结论自由基所引发的脂质过氧化反应损伤是SAP发病过程中的重要因素之一,MLT及VitC可有效地减轻SAP时脂质过氧化反应损伤,明显减轻SAP时胰腺的病理改变,两者联合使用效果更佳。     

抗氧化剂对去卵巢大鼠骨密度和血清生化指标的影响

目的 研究抗氧化剂维生素C、E及还原型谷胱甘肽(GSH)不同配伍用药方法对去卵巢大鼠骨密度及血清生化指标的影响.方法 4月龄雌性SD大鼠70只,随机取50只行双侧卵巢切除术,20只行假手术.3个月后随机从手术组和假手术组各取10只大鼠检测体重、子宫湿重、左侧股骨及腰椎骨密度和血清生化指标Ca2+、肌酐、碱性磷酸酶(ALP)水平,以确定骨质疏松模型建立成功.确定模型建立成功后,其余动物分为A(假手术)、B(去卵巢生理盐水对照组)、C(维生素C+维生素E)、D(GSH)、E(维生素C+维生素E十GSH)5组,每组10只.药物用最维牛素C(750 mg·kg-1·d-1)、GSH(125 mg·kg-1·d-1)腹腔注射,维牛素E(250 mg·kg-1·d-1)灌胃,模型组每天以生理盐水腹腔注射.3个月后,检测各组动物左侧股骨及腰椎骨密度和血清生化指标.结果 抗氧化剂治疗3个月后,与模型组相比,左侧股骨及腰椎骨密度三个治疗组均明显增加,其中D、E组增加最显著;血清ALP各组均显著降低;超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平和血清抑制OH-能力D、E组显著升高;丙二醛水平C、D组显著降低;各组血清Ca2+水平无明显改变.结论 抗氧化剂维生素C、维生素E及GSH显著增加去卵巢骨质疏松模型大鼠骨密度,阻止血清抗氧化成分(SOD、GSH-Px)减少,提高血清抑制OH-能力,降低脂质过氧化物丙二醛.     

肝细胞癌变过程中维生素E水平改变及其作用机制研究

目的 探讨维生素Ｅ（Ｖｉｔ Ｅ）水平在肝细胞癌变过程中的改变与作用机制。方法 用２－ＦＡＡ制备大鼠肝癌动物模型,在肝细胞癌变过程中观察其肝组织学、肝总ＲＮＡ水平及血浃ＶｉｔＥ含量的动态改变,并对不同肝病患者血清中ＶｉｔＥ的浓度进行了分析。结果 在肝细胞癌变过程中,鼠血清中ＶｉｔＥ含量呈逐渐降低,而鼠肝总ＲＮＡ水平逐渐增加趋势;在急性肝炎、慢性肝炎、肝硬变和肝癌患者血清中ＶｉｔＥ含量均显著低于正常对     

Effect of naked eukaryotic expression plasmid encoding rat augmenter of liver regeneration on acute hepatic injury and hepatic failure in rats

AIM: To study the protective effect of eukaryotic expression plasmid encoding augmenter of liver regeneration (ALR) on acute hepatic injury and hepatic failure in rats. METHODS: The PCR-amplified ALR gene was recombined with pcDNA3 plasmid, and used to treat rats with acute hepatic injury. The rats with acute hepatic injury induced by intraperitoneal injection of 2 mL/kg 50% carbon tetrachloride (CCl4) were randomly divided into saline control group and recombinant pcDNA3-ALR plasmid treatment groups. Recombinant pcDNA3-ALR plasmid DNA (50 or 200 μg/kg) was injected into the rats with acute hepatic injury intraven ously, intraperitoneally, or intravenously and intraperitoneally in combination 4 h after CCl4 administration, respectively. The recombinant plasmid was injected once per 12 h into all treatment groups four times, and the rats were decapitated 12 h after the last injection. Hepatic histopathological alterations were observed after HE staining, the expression of proliferating cell nuclear antigen (PCNA) in liver tissue was detected by immunohistochemical staining, and the level of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) was determined by biochemical method. The recombinant plasmid DNA (200 μg/kg) and saline were intraperitoneally injected into the rats with acute hepatic failure induced by intraperitoneal injection of 4 mL/kg 50% CCl4 after 4 h of CCl4 administration, respectively. Rats living over 96 h were considered as survivals. RESULTS: The sequence of ALR cDNA of recombinant pcDNA3-ALR plasmid was accordant with the reported sequence of rat ALR cDNA. After the rats with acute hepatic injury were treated with recombinant pcDNA3-ALR plasmid, the degree of liver histopathological injury markedly decreased. The pathologic liver tissues, in which hepatic degeneration and necrosis of a small amount of hepatocytes and a large amount of infiltrating inflammatory cells were observed, and they became basically normal in the most effective group after four times of injection of recombinant pcDNA3-ALR plasmid. The indexes of PCNA significantly increased in the recombinant pcDNA3-ALR plasmid treatment groups compared to model group. The level of serum AST and ALT remarkably reduced in recombinant pcDNA3-ALR plasmid treatment groups compared to model group. The results showed that the effect of 200 μg/kg recombinant pcDNA3-ALR plasmid in the rats with acute liver injury was stronger than that of 50 μg/kg pcDNA3-ALR DNA. The effect of intravenous injection of recombinant pcDNA3 ALR plasmid was better. After the rats with acute hepatic failure were treated with recombinant pcDNA3-ALR plasmid, the survival rate (40%) significantly increased in treatment groups compared to control group (15%, P<0.01). CONCLUSION: The ALR gene may play an important role in relieving acute hepatic injury and hepatic failure by promoting hepatic cell proliferation and reducing level of AST and ALT in CCl4-intoxicated rats.     

Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin e in nonalcoholic steatohepatitis.

BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) is a frequent liver disease that can progress to cirrhosis and for which there is no recognized therapy. UDCA and vitamin E have been considered separately as therapeutic options and have not been shown to be effective. This study tested their combination. METHODS: Patients with elevated aminotransferase levels and drinking less than 40 g alcohol/week with biopsy-proven NASH were randomly assigned to receive UDCA 12-15 mg.kg-1.day-1 with vitamin E 400 IU twice a day (UDCA/Vit E), UDCA with placebo (UDCA/P), or placebo/placebo (P/P). After 2 years, they underwent a second liver biopsy. Biopsy specimens were collected, blinded, and scored by a single liver pathologist. RESULTS: Forty eight patients were included, 15 in the UDCA/Vit E group, 18 in the UDCA/P group, and 15 in the P/P group; 8 patients dropped out, none because of side effects. Baseline parameters were not significantly different between the 3 groups. Body mass index remained unchanged during the study. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels diminished significantly in the UDCA/Vit E group. Neither the AST nor the ALT levels improved in the P/P group and only the ALT levels in the UDCA/P group. Histologically, the activity index was unchanged at the end of the study in the P/P and UDCA/P groups, but it was significantly better in the UDCA/Vit E group, mostly as a result of regression of steatosis. CONCLUSIONS: Two years of treatment with UDCA in combination with vitamin E improved laboratory values and hepatic steatosis of patients with NASH. Larger trials are warranted.     

Influence of estradiol and testosterone on carbon tetrachloride-induced liver damage in the rat

The aim of the study was to know influences of estrogen and testosterone on carbon tetrachloride-induced liver damage in male Wistar rats. One hundred and two rats were divided into following six groups on the basis of the treatment: olive oil as control (O), carbon tetrachloride (0.1 ml/100 g, C), estradiol benzoate (0.1 mg/100 g, E), testosterone propionate (5 mg/100 g, T), C + E and C + T, in which each drug was intraperitoneally injected twice per week for consecutive 12 weeks. In the C + E group, decreases in serum albumin level at the 4th week and total cholesterol level at the 8th week seemed to be suppressed. And fibrotic change and fatty change were weak on the histological observation. However, hepatocellular hyperplasia was observed in 40% cases after the 8th week. On the flow cytometry analysis of the liver at the 4th week, an enhancement of hepatocellular proliferation was shown. Survival rate of the C + E group rats was lower than C group rats. On the other hand, in the C + T group, liver injury occurred in the same grade as C group, and the survival rate was worst among all six groups. These results suggest that simultaneous administration of estrogen with carbon tetrachloride could reduce hepatic injury, though it might cause hepatocellular hyperplasia.     

藏红花对酒精及酒精加四氯化碳所致大鼠肝损伤的防治作用

目的：探索藏红花对酒精及酒精四氯化碳所致大鼠肝损伤的防治作用。方法：取Wistar雄性大鼠设5组,分别灌胃生理盐水（A）、白酒（B）、白酒加藏红花（C）,白酒加CCl4(D),在D组基础上加用藏红花（E）对5组大鼠血清ALT和肝脏组织学病变进行比较。结果：藏红花能降低白酒和四氯化碳引起的ALT升高（P＜0．05）;B、C组及D、E组互比肝脏组织学改变有明显差异（P＜0．05）。结论：藏红花对酒精及酒精四氯化碳所致肝损伤有一定的防治作用。