甘草类黄酮对四氯化碳致小鼠急性肝损伤的影响

甘草类黄酮(GF)是从甘草根中提得。本文结果表明,预先ig GF 200,400,600mg·kg^-1·d^-1×2d能显著降低CCl₄所致血清谷丙转氨酶,乳酸脱氢酶活性的升高以及肝内丙二醛含量的增加,其作用呈剂量依赖性。GF可减轻CCl₄所致的肝脏坏死,但对血清内酶的活性没有抑制作用,也不减少正常小鼠血清中酶的活性。GF的肝保护作用可能与其抗脂质过氧化作用有关。     

阿魏酸钠对甘油致小鼠肾脏氧化性损伤的拮抗效应阿魏酸钠对甘油致小鼠肾脏氧化性损伤的拮抗效应

目的从氧化应激角度,探讨阿魏酸钠对实验动物中毒性肾损害的防治作用。方法建立甘油所致小鼠急性肾小管损伤模型,观察不同剂量的阿魏酸钠对肾损伤小鼠肾功能指标、抗氧化指标和组织学的影响。结果在甘油注射后6和72 h,阿魏酸钠100～200 mg·kg^-1 ip能剂量依赖性的降低甘油所致血清尿素氮、肌酐和N-乙酰-β-葡糖苷酶的升高。阿魏酸钠200 mg·kg^-1减少肾组织丙二醛生成,提高肾脏谷胱甘肽含量及谷胱甘肽过氧化物酶、谷胱甘肽S-转移酶、过氧化氢酶和超氧化物歧化酶活性,且可明显减轻肾组织病理改变。结论阿魏酸钠对甘油致肾损伤有防治作用,其机制与增强肾脏抗氧化功能有关。     

黄芪多糖对内毒素致小鼠毒性损伤的作用

本文结果表明,预先给予黄芪多糖(APS)ip30,60,100mg·kg^-1·d^-1×7d能明显提高内毒素(25mg·kg^-1·ip)中毒小鼠的存活率,APSip 100mg·kg^-1·d^-1×7d,能完全解除内毒素的致死作用,对内毒素中毒鼠肝脏内ATP含量及EC值下降具有拮抗作用。上述作用均呈剂量依赖性。APSip 60,100mg·kg^-1·d^-1×7d能明显拮抗内毒素处理小鼠肝匀浆中MDA升高及GSH降低。电镜显示APS对内毒素处理小鼠肝脏线粒体结构的损伤具有保护作用。     

解酒饮对小鼠急性肝损伤的保护作用

目的 探讨解酒饮对小鼠急性四氯化碳（CCl₄）肝损伤的保护作用。方法 将60只小鼠分为正常组、联苯双酯组、模型组（0.3% CCl₄腹腔注射）和解酒饮组（按剂量分为25,12.5,6.25 g·kg^-1组,灌胃25 ml·kg^-1,连续灌胃8 d）,每组各10只。造模12 h后,用全自动生化仪测定血清丙氨酸转移酶（ALT）、天门冬氨酸转移酶（AST）、白蛋白（ALB）、球蛋白（GLB）、总蛋白（TP）的活性。肝组织匀浆测定丙二醛（MDA）含量、超氧化物歧化酶（SOD）和谷胱甘肽（GSH）活性。并对肝组织进行组织形态学检查。免疫组化方法检测肝脏MnSOD、bcl-2、caspase-3的表达情况。结果 解酒饮能降低CCl₄诱导的急性肝损伤小鼠升高的血清ALT、AST水平。解酒饮25 g·kg^-1降低肝匀浆升高的MDA水平,同时升高肝匀浆中的SOD和GSH酶活性,改善肝组织的病理形态。免疫组化结果显示,解酒饮25 g·kg^-1可以上调MnSOD、bcl-2表达水平,下调caspase-3表达水平。结论 解酒饮可能通过提高肝脏抗氧化能力,抑制肝细胞凋亡,对小鼠急性CCl₄肝损伤有一定的保护作用。     

双环醇对四环素诱发小鼠急性脂肪肝的保护作用

研究双环醇对四环素诱发小鼠急性脂肪肝的影响。小鼠一次腹腔注射四环素(180 mg·kg^-1) 24 h后，收集血样和肝组织，采用生化法测定肝脏甘油三酯(triglyceride，TG)、胆固醇(cholesterol，CHO)、谷胱甘肽(glutathione，GSH)含量，以及血清脂质和转氨酶水平；光谱法测定小鼠线粒体脂肪酸β-氧化速率以及肝脏极低密度脂蛋白(very low density lipoprotein，VLDL，TG)分泌速率。结果表明，双环醇(150及300 mg·kg^-1)连续灌胃给药3次可以不同程度地保护四环素引起的小鼠肝脏TG和CHO升高以及血清谷丙转氨酶(alanine aminotransferase，ALT)、谷草转氨酶(aspartate aminotransferase，AST)升高和脂质异常。双环醇(300 mg·kg^-1)还可减轻四环素诱发小鼠肝脏丙二醛(malondialdehyde，MDA)生成增加和GSH水平降低，并能抑制肝线粒体脂肪酸β-氧化速率下降。双环醇(300 mg·kg^-1)可部分逆转四环素所致小鼠肝脏VLDL(TG)分泌速率的减少。由此可见，双环醇对四环素诱发小鼠急性脂肪肝具有明显的保护作用，其作用机制与保护肝线粒体β-氧化功能、改善肝脂蛋白分泌及转运以及抑制肝脏脂质过氧化密切相关。     

苦参及苦参碱对小鼠肝脏和神经行为学的影响

目的 观察苦参及苦参碱对小鼠肝脏毒性及神经行为学功能的影响。方法 50只ICR小鼠随机分为空白组、苦参1.5,15 g·kg^-1剂量组,苦参碱10,40 mg·kg^-1剂量组,每天给药1次,连续灌胃60 d;首次给药前和末次给药后测定小鼠自主活动及爬竿法平衡协调能力,末次给药后,测定小鼠体质量、血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(AKP)水平及肝组织SOD活性和MDA含量。结果 与空白组相比,给药组小鼠体质量降低、自主活动数减少,平衡协调能力下降;各给药组AST、ALT、AKP活性均有差异,其中苦参1.5 g·kg^-1,苦参碱10,40 mg·kg^-1组AST、ALT、AKP活性有显著性差异(P<0.05或P<0.01);肝组织SOD活性无明显变化,MDA含量显著上升。结论 小鼠连续灌胃苦参及苦参碱可引起肝脏毒性和神经行为学的改变。     

阿魏酸钠部分减轻氢化泼尼松引起的小鼠肝脏毒性

氢化泼尼松(Pred)20mg·kg^-1可明显增高小鼠sGPT与sGST水平,增加肝匀浆MDA含量及肝微粒体与线粒体膜流动性。表明Pred致sGPT及sGST水平增高与肝脂质过氧化作用增强及膜流动性改变有关。经1g阿魏酸钠(SF)100mg·kg^-1使sGPT与sGST水平降低,肝脏MDA含量减少,但sGPT与MDA仍高于正常对照组水平。肝微粒体膜流动性恢复,线粒体膜流动性进一步增高。电镜观察亦见线粒体仍有损害,提示SF不能完全对抗Pred所致肝损害。     

Kappa-晒化卡拉胶对实验动物的抗心律失常作用

Kappa-硒化卡拉胶是一含硒有机化合物。ip 9 mg·kg^-1·d^-1×5d或单次ig 35,70,140mg·kg^-1能显著提高乌头碱致大鼠HA的阈剂量,此作用可与Na₂SeO₃ 1 mg·kg^-1·d^-1×5d ip比拟.随着Kappa-硒化卡拉胶ig剂量增加,尚可提高乌头碱所致VE,VT和VF的阈剂量。ip 9mg·kg^-1·d^-1×5 d或ig 70mg·kg^-1能提高BaCl₂致大鼠或哇巴因致豚鼠HA的阈剂量。对BaCl₂致大鼠VF或哇巴因致豚鼠VE的阈剂量,分别在ig70mg·kg^-1与140mg·kg^-1时有提高,而ipNa₂SeO₃ 1 mg·kg^-1·d^-1×5d无此明显影响。     

化合物ALI-57对小鼠急性药物性肝损伤活性的初步评价

目的 初步评价化合物ALI-57对对乙酰氨基酚诱导的急性药物性肝损伤活性。方法 48只C57/BL6小鼠随机分为6组，即正常组、模型组、阳性对照组(乙酰半胱氨酸300 mg·kg^–1)和化合物ALI-57低、中、高剂量组(75，150，300 mg·kg^–1)，每组8只。连续灌胃给药3 d，末次给药1 h后，除正常组外其余各组小鼠按350 mg·kg^–1的剂量腹腔注射对乙酰氨基酚进行造模，禁食不禁水，8 h后腹腔静脉取血，进行血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)，肝组织中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)以及谷氨酸脱氢酶(GDH)的检测；提取肝组织用于病理HE染色检查。结果 与正常组比较，模型组血清中ALT、AST水平显著升高，肝组织中MDA和GDH含量升高，而SOD和GSH活性水平下降，组织HE病理染色结果显示肝组织损伤明显增加。与模型组比较，化合物ALI-57中、高剂量组血清中ALT、AST水平显著降低(P<0.05)，肝组织中MDA和GDH含量明显下降(P<0.05)，而肝组织中SOD和GSH活性水平显著升高(P<0.05)，低剂量组与模型组比较无显著性差异。结论 化合物ALI-57能够通过降低氧化应激和提高抗氧化能力对对乙酰氨基酚诱导的急性药物性肝损伤发挥明显的保护作用。     

联苯双酯对大鼠黄曲霉毒素B1代谢及肝毒性的影响

目的研究抗肝炎药联苯双酯对大鼠黄曲霉毒素B₁代谢和肝毒性的影响。方法大鼠po联苯双酯300 mg·kg^-1·d^-1, 连服3 d后ip黄曲霉毒素B₁1.5 mg·kg^-1。给黄曲霉毒素B₁16 h后测定血清ALT和AST水平,观察联苯双酯对黄曲霉毒素B₁引起肝损伤的保护作用以及对体外代谢的影响。结果联苯双酯(300 mg·kg^-1·d^-1,连服3 d)可明显降低黄曲霉毒素B₁引起的大鼠血清转氨酶升高，增加低毒代谢产物AFM₁的生成。联苯双酯还可增加大鼠肝脏细胞色素P450总量和胞浆GSH含量，诱导P450 2B1介导的PROD和GST的活性。此外，联苯双酯对P450 3A介导的红霉素脱甲基酶和P450 1A介导的EROD也有一定的诱导作用。结论联苯双酯可通过增加大鼠肝脏对AFB₁代谢的解毒功能起到肝保护作用。     

d-α-生育酚对乙醇引发的肝脏氧化应激的影响

目的观察d-α-生育酚对乙醇诱发的小鼠肝脏氧化应激的影响并探讨其机制。方法昆明种小鼠每天给予2.4g.kg-1bw乙醇后,再给予3个不同剂量的d-α-生育酚(25、50、100mg·kg-1bw.d-1),同时设正常对照组和乙醇对照组(乙醇2.4g·kg-1bw.d-1),连续灌胃60d后,测定肝脏超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、Na+,K+-ATP酶(Na+,K+-ATPase)、Ca2+,Mg2+-ATP酶(Ca2+,Mg2+-ATPase)、谷胱甘肽-S转移酶(GST)活力及丙二醛(MDA)的含量。结果小鼠摄入乙醇60d后,肝脏氧化应激水平明显增高。除Ca2+,Mg2+-ATPase以外,其余各项指标与正常对照组相比,差异均有显著性(P<0.05)。50mg·kg-1bw.d-1d-α-生育酚干预后,与乙醇对照组相比,GSH-Px、SOD、GST、Na+,K+-ATPase活力明显升高,MDA含量显著下降。其中,GSH-Px、Na+,K+-ATPase、MDA等3个指标在25mg·kg-1bw.d-1d-α-生育酚干预时亦出现同样的变化。结论适宜剂量的d-α-生育酚可以通过直接抑制脂质过氧化对乙醇诱发的肝脏氧化应激起保护作用。     

cAMP在LPS及BCG +LPS诱导的免疫性肝损伤中的作用比较(英文)

目的　比较LPS、BCG +LPS诱导的免疫性肝损伤模型的特点及肝中cAMP的变化 ,以建立合适的动物模型 ,并为药物作用及肝损伤机制探讨提供参考。方法　昆明种小鼠 ,分为 5组 :①对照组 ;②BCG组 (ip 1mg·kg- 1 BCG ,7d后处理动物 ) ;③LPS 0 2mg ;④LPS 0 4mg组 (分别ip 0 2 ,0 4mg·kg- 1 ,6h后处理动物 ) ;⑤BCG +LPS组 (ip 1mg·kg- 1 BCG 7d后ip 0 2mg·kg- 1 LPS 6h后处理动物 )。取血清 ,测定ALT、GST活性 ;HE染色 ,光镜观察组织损伤情况 ;制备肝匀浆 ,放射免疫法测定cAMP含量。结果　组织学检查表明 ,给予BCG或LPS均能引起中性粒细胞浸润。单独给予BCG或 0 2mg·kg- 1 LPS未见明显的肝组织损害 ,但经BCG预处理后 ,0 2mg·kg- 1 LPS可使血清ALT、GST水平显著增高。单独给予 0 4mg·kg- 1 LPS也能引起明显的肝组织损伤。经BCG预处理后的小鼠肝组织内cAMP含量明显下降 ,而单独LPS刺激 ,则使肝内cAMP含量呈剂量依赖性增高。结论　LPS、BCG +LPS均能引起典型的免疫性肝损伤 ,经BCG预处理 ,能增强内毒素刺激诱导的肝脏毒性。不同的免疫性肝损伤模型所致肝内cAMP含量的变化不同 ,在进行机制研究及药物药理作用研究时应予以考虑     

复方枳椇子制剂对乙醇所致小鼠肝损伤的保护作用

目的研究复方枳椇子制剂(CPH)对乙醇所致小鼠肝损伤的保护作用。方法采用56%乙醇灌胃的方法来诱导小鼠急性肝损伤模型。将小鼠随机分为空白组,模型组,CPH(1,2,4 g.kg-1)组和阳性(XJGGK)组。测定小鼠血清中谷丙转氨酶(ALT),谷草转氨酶(AST),甲胎蛋白(AFP),以及肝组织中丙二醛(MDA),超氧化物歧化酶(SOD),谷胱甘肽过氧化物酶(GSH-Px)的含量或活性,并进行小鼠肝病理组织学检查。结果 CPH可显著降低饮酒小鼠血清中ALT、AST含量的升高,降低MDA含量,增加SOD活性和GSH-Px含量,并能改善乙醇损伤小鼠肝病理组织结构,但CPH提取物对饮酒小鼠AFP水平没有明显影响。结论 CPH对乙醇所致小鼠肝损伤具有保护作用,其机制可能与清除氧自由基和抗脂质过氧化有关,为将CPH开发成安全、有效的功能食品提供依据。     

Deletion of circadian gene Per1 alleviates acute ethanol-induced hepatotoxicity in mice

The severity of ethanol-induced liver injury is associated with oxidative stress and lipid accumulation in the liver. Core circadian clock is known to mediate antioxidative enzyme activity and lipid metabolism. However, the link between circadian clock and ethanol-induced hepatotoxicity remains unclear. Here we showed that extents of acute ethanol-induced liver injury and steatosis in mice exhibit circadian variations consistent with hepatic expression of Period (Per) genes. Mice lacking clock gene Per1 displayed less susceptible to ethanol-induced liver injury, as evidenced by lower serum transaminase activity and less severe histopathological changes. Ethanol-induced lipid peroxidation was alleviated in Per1?/? mice. However, Per1 deletion had no effect on antioxidants depletion caused by ethanol administration. Ethanol-induced triglycerides (TG) accumulation in the serum and liver was significantly decreased in Per1?/? mice compared with that in wild-type (WT) mice. Analysis of gene expression in the liver revealed peroxisome proliferators activated receptor-gamma (PPARγ) and its target genes related to TG synthesis are remarkably down-regulated in Per1?/? mice. HepG2 cells were treated with ethanol at 150 mM for 3 days. Per1 overexpression augmented lipid accumulation after treatment with ethanol in HepG2 cells, but had no effect on ethanol-induced oxidative stress. Expression of genes related to lipogenesis, including PPARγ and its target genes, was up-regulated in cells overexpressing Per1. In conclusion, these results indicated that circadian rhythms of ethanol-induced hepatotoxicity are controlled by clock gene Per1, and deletion of Per1 protected mice from ethanol-induced liver injury by decreasing hepatic lipid accumulation.     

Protective effects of 3′-daidzein sulfonate sodium on chronic hepatic injury by regulating the T lymphocyte subsets in mice

OBJECTIVE To explore the protective effects of 3′-daidzein sulfonate sodium on chronic hepatic injury induced by carbon tetrachloride(CCl4)in mice and investigate the mechanism about regulating the T lymphocyte subsets.METHODS Healthy Kunming male mice were randomly divided in 5groups:control group,model group,bifendate positive control group(2.5mg·kg-1),low and high dose 3′-daidzein sulfonate sodium groups(0.1and 0.3mg·kg-1).The chronic hepatic injury mice were made by intraperitoneal injection of 10% CCl4 plant oil solution twice a week,and sustained for six weeks.At the same time,the mice were treated with normal saline,bifendate(2.5mg·kg-1)and 3′-daidzein sulfonate sodium(0.1and 0.3mg·kg-1),respectively by ig administration once a day and continued for six weeks.After the last administration,the mice blood and liver were taken.Using automatic biochemical analyzer survey the activity of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)in serum.Flow cytometry was used to detect T lymphocyte subsets,enzymes analysis technique was used to observe the liver function(CD3+,CD4+and CD8+),HemateinEosin stain was used to explore the changes in liver morphology.RESULTS The level of ALT and AST in the serum in model group mice increased significantly.While the level of ALT and AST in the serum in 3′-daidzein sulfonate sodium(0.1 or 0.3mg·kg-1,ig)groups mice decreased compared with the model group(P<0.05).And compared with the model group,the ratios of CD3+,CD4-CD8-and CD4+/CD8+ decreased,and the ratios of CD8+ increased in 3′-daidzein sulfonate sodium groups(0.1 and 0.3mg·kg-1,ig;P<0.05).CONCLUSION 3′-daidzein sulfonate sodium have a protective effect on CCl4-induced liver injury mice,and it can result in the changes of T lymphocyte subsets,which may be one of the factors leading to hepatic injury by CCl4.     

阿魏酸钠对异烟肼和利福平肝损害小鼠的保护作用

目的：观察阿魏酸钠对异烟肼(INH)和利福平(RFP)肝毒性的保护作用。方法：分别测定血清谷丙转氨酶(ALT)的活性，肝匀浆中谷胱甘肽(GSH)及脂质过氧化物丙二醛(MDA)的含量，肝微粒体中细胞色素P450及其亚型2E1的活性。结果：阿魏酸钠可对抗INH和RFP合用引起的肝指数、血清ALT水平、肝匀浆中的MDA含量，以及细胞色素P450与亚型P450 2E1活性的升高，增加肝匀浆中GSH含量。病理学检查，阿魏酸钠明显减轻肝细胞的变性和坏死。结论：阿魏酸钠时INH和RFP肝毒性的保护作用与保护肝细胞膜、抑制脂质过氧化反应、清除自由基、降低RFP诱导的细胞色素P450酶系统有关。     

Modulatory influence of noscapine on the ethanol-altered hepatic biotransformation system enzymes, glutathione content and lipid peroxidation in vivo in rats.

The modulatory potential of noscapine, an opium alkaloid was assessed on the ethanol-induced changes in hepatic drug metabolizing enzyme systems, glutathione content and microsomal lipid peroxidation. Noscapine was administered orally to male Wistar rats at a dose level of 200 mg/kg bw alone as well as in combination with 50% ethanol (v/v) for 5 days. Noscapine administration was associated with a approximately 91% decrease in hepatic microsomal cytochrome P-450 content. A decline of approximately 36% was observed in the NADPH-cytochrome c reductase activity on noscapine administration. The lowering of cytochrome P-450 levels on noscapine administration was accompanied by a concomitant increase in heme oxygenase activity as well as serum bilirubin levels. Our results indicate that the combination dosage of noscapine and ethanol antagonised the ethanol-induced elevation of cytochrome P-450 levels. Noscapine fed rats had decreased glutathione (GSH) content and enhanced lipid peroxidation compared to control rats as indexed by MDA method. Further, noscapine and ethanol coexposure produced a more pronounced elevation in lipid peroxidation and the glutathione levels also decreased significantly. We speculate on the basis of our results that the significant enhancement of lipid peroxidation on combination dosage of noscapine and ethanol is a consequence of depletion of glutathione to certain critical levels. The inhibition of glutathione-S-transferase (GST) as well as lowering of cytochrome P-450 suggests that the biotransformation of noscapine and ethanol is significantly altered following acute coexposures.     

水黄皮根乙酸乙酯萃取物对大鼠乙醇型胃黏膜损伤的保护作用(英文)

目的研究水黄皮根乙酸乙酯萃取物(PREA)对乙醇致胃黏膜损伤的治疗作用。方法建立乙醇致大鼠胃黏膜损伤模型,通过观察胃组织病理学改变、计算胃黏膜损伤指数、检测胃黏膜组织一氧化氮(NO)、丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性评价PREA对乙醇型胃黏膜损伤的保护作用。采用幽门结扎模型,观察PREA对大鼠胃液分泌和胃黏液分泌的影响。结果与模型组比较,PREA可剂量依赖性地降低乙醇所致胃黏膜损伤指数,明显改善胃黏膜损伤的病理变化,抑制乙醇引起的胃黏膜MDA含量升高及NO水平和SOD活性降低,并显著减少胃酸分泌、抑制游离胃酸酸度和总酸度,对胃蛋白酶活性没有明显影响。另外,可显著抑制幽门结扎模型大鼠胃腔游离黏液以及胃壁结合黏液的分泌。结论PREA对乙醇型胃黏膜损伤具有明显的保护作用,提示PREA可能成为预防或治疗乙醇所致胃损伤的药物。     

Combined effects of vitamin C, vitamin E, and sodium selenate supplementation on absolute ethanol-induced injury in various organs of rats

In this study, the effect of combination of vitamin C (ascorbic acid), vitamin E (alpha -tocopherol), and selenium (sodium selenate) on ethanol-induced liver and intestine injury in rats was investigated. The ethanol-induced injury was produced by the administration of 1 ml of absolute ethanol to each rats. Animals received vitamin C (250 mg/kg), vitamin E (250 mg/kg), and sodium selenate (Se) (0.5 mg/kg) for 3 days; 1 h after the final antioxidant administration, they were sacrificed. Lipid peroxidation and glutathione levels, catalase (CAT), lactate dehydrogenase (LDH), superoxide dismutase (SOD), and glutathione peroxidase (GP(x)) activities were determined in liver and intestine tissues. Myeloperoxidase (MPO), aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT) were determined in liver tissue. Also, CAT activity, urea, creatinine, uric acid, and total lipid levels were determined in serum samples. In the ethanol group, serum urea, creatinine, uric acid, and total lipid levels; liver and intestine LDH; liver MPO, AST, ALP, ALT, and GGT activities; and liver and intestine LPO levels increased, whereas serum CAT activity, liver and intestine GSH levels, and CAT, SOD, and GP(x) activities decreased. On the other hand, treatment with vitamin C, vitamin E, and Se reversed these effects. As a result of these findings, we can say that the combination of vitamin C, vitamin E, and selenium has a protective effect on ethanol-induced changes in lipid peroxidation, glutathione levels, and antioxidant enzyme activities in liver and intestine tissues, and in some serum parameters of rats.