六味五灵片对四氯化碳致大鼠肝纤维化的保护作用

目的研究六味五灵片对四氯化碳(CCl4)所致大鼠肝纤维化的保护作用。方法用CCl4-植物油溶液腹腔注射造模,将造模成功的大鼠随机分为5组,每组12只,分别为模型组、复方鳖甲软肝片组、六味五灵片低剂量组(4 g.kg-1)、六味五灵片中剂量组(8 g.kg-1)、六味五灵片高剂量组(16 g.kg-1)。以血清中谷草转氨酶(AST)、谷丙转氨酶(ALT)、透明质酸(HA)、层粘连蛋白(LN)及羟脯氨酸(HyP)和肝组织中还原型谷胱甘肽(GSH)、超氧化物歧化酶(SOD)及丙二醛(MDA)为评价指标,以肝组织Masson染色追踪其肝纤维化程度。结果六味五灵片能明显降低CCl4所致的大鼠血清中ALT、AST、HA、LN和HyP的含量(P<0.05),降低肝组织中的MDA含量(P<0.05),明显升高肝组织中的GSH和SOD含量(P<0.05),肝组织纤维化变性明显减轻,肝组织结构比较完好。结论六味五灵片对四氯化碳所致大鼠肝纤维化具有保护作用。     

Effect of 'Arogyavardhini' against carbon tetrachloride induced hepatic damage in albino rats

'Arogyavardhini'-an indigenous formulation was evaluated for its hepatoprotective activity in rats, using two models of carbon tetrachloride (CCl4) hepatic damage, one simulating vital hepatitis and the other simulating fatty change. The protective effect was assessed from serum aspartate transaminase (AST) and alkaline phosphatase levels and from histopathological changes in liver. The results revealed that 'Arogyavardhini' (5 mg/100g, PO daily) was effective in minimizing the changes in serum levels of AST and alkaline phosphatase induced by CCI. The protective effect was also evident on histopathological examination.     

海补乐宝软胶囊对CCl4致大鼠实验性慢性肝损伤的保护作用

目的 观察海补乐宝软胶囊对大鼠实验性慢性肝损伤的保护作用.方法 设实验样品组、阴性对照组、模型组和阳性对照组.各组大鼠分别于第1、3、6、8周ip四氯化碳或玉米油,并在每周作相应的ig给药,于第8周处死所有大鼠,查血常规和相关酶活性,并取组织作病理切片,光镜下检查、评分.结果 样品组动物血清中ALT和AST活性较模型组显著降低,肝组织病变亦明显减轻.结论 海补乐宝软胶囊对大鼠化学性慢性肝损伤具有辅助保护作用.     

褪黑素对大鼠肝纤维化的影响及部分机制研究

目的探讨褪黑素(melatonin,MEL)对大鼠肝纤维化的影响及部分机制。方法 111只雄性SD大鼠随机分为6组:正常对照组、模型对照组、N-乙酰-L-半胱氨酸组(N-ac-etyl-L-cysteine,NAC)组、褪黑素低、中、高剂量组(剂量分别为2.5、5、10 mg.kg-1)。采用四氯化碳(carbon tetrachloride,CCl4)制备大鼠肝纤维化模型,同时腹腔注射褪黑素,HE染色和VG胶原纤维染色观察肝脏病理改变;生化法测定肝脏丙二醛(malondialdehyde,MDA)含量和谷胱甘肽过氧化物酶(glutathione peroxidase,GPx)、超氧化物歧化酶(superox-ide dismutase,SOD)活性;RT-PCR法测定肝组织中α1(I)前胶原(α1(I)procollagen)mRNA表达;原位灌注加密度梯度离心法分离正常SD大鼠肝脏星状细胞,在培养的肝星状细胞中加入脂多糖(lipopolysaccharide,LPS)进行刺激,用MTT法测定不同浓度的MEL对肝星状细胞增殖的抑制作用。结果和模型组比较,MEL(10 mg.kg-1)组肝纤维化评分较低(P<0.05),MEL能明显降低肝匀浆MDA含量,升高SOD、GPx活性,MEL(10 mg.kg-1)组、NAC组大鼠肝组织α1(I)型前胶原mRNA表达明显减少(P<0.05);培养的肝星状细胞经LPS刺激后A值增大,与LPS组相比,LPS+NAC组和LPS+MEL(0.1 mmol·L-1)组A值明显减小(P<0.05)。结论 MEL对大鼠肝纤维化具有改善作用,其机理可能与抗氧化、抑制前胶原基因转录和抑制肝星状细胞增殖有关。     

Antioxidative effect of chitosan on chronic carbon tetrachloride induced hepatic injury in rats

Carbon tetrachloride (CCl(4)) is a toxic material known to induce lipid peroxidation and liver damage. To determine if chitosan has antioxidative effects on CCl(4)-induced liver injury, we administered 1 ml/kg of CCl(4) resolved in a 50% corn oil solution to rats every week by intraperitoneal injection. Chitosan (200 mg/kg body weight per day, MW 380,000 Da) was administered to the CCl(4) + chitosan treated rats by oral gavage during the experimental period. Chitosan significantly decreased liver thiobarbituric acid reactive substances (TBARS) and increased antioxidant enzyme activities (catalase and superoxide dismutase (SOD)). Fatty acid composition was not remarkably changed by chitosan; only arachidonic acid (20:4n-6) levels were significantly altered by CCl(4). Chitosan administration in the present experiment did not restore the decreased delta5-desaturase activity. In addition, chitosan supplementation did not prevent the CCl(4) induced degradation of CYP2E1. In conclusion, our results suggest that chitosan has antioxidative but not detoxifying effects on chronic CCl(4) induced hepatic injury in rats.     

大黄酸抑制四氯化碳诱导的大鼠肝纤维化形成

目的:观察大黄酸对实验性肝纤维化的影响.方法:采用60％的四氯化碳(CCl_4)及5％的乙醇制备肝纤维化动物模型,分别用小剂量、大剂量大黄酸(25 mg/kg,100 mg/kg体重)干预,测定血清丙氨酸氨基转移酶(ALT)、透明质酸(HA)、Ⅲ型前胶(PC-Ⅲ)及肝组织丙二醛(MDA)含量,免疫组化方法观察转化生长因子 β1(TGF-β1)、α平滑肌肌动蛋白(α-SMA)的表达情况,并观察肝组织胶原面积及病理变化.结果:大黄酸组较模型组:(1)血清ALT、HA、PC-Ⅲ水平及肝组织中MDA含量显著降低(P<0.01);(2)肝组织中TGF-β1,α-SMA的表达显著减少(P<0.05或P<0.01);③肝组织胶原面积明显减少,纤维化程度明显改善(P<0.05或P<0.01).结论:大黄酸具有保肝作用和抑制肝纤维化作用,其作用机制可能与其抗炎、抗氧化作用及抑制HSC活化、抑制TGF-β1作用有关.     

珍珠梅水提取物对四氯化碳所致大鼠急性肝损伤的保护作用

目的研究珍珠梅水提取物大鼠急性肝损伤的保护作用。方法大鼠皮下注射CCh制备急性肝损伤模型，用自动生化分析仪测定血清ALT、AST活性；比色分析法测定血清SOD、GSH-Px活性和MDA含量。结果CCh肝损伤大鼠血清ALT、AST活性和MDA含量升高，SOD、GSH-Px活性降低；珍珠梅水提物和联苯双酯灌胃给药能显著降低CCh肝损伤大鼠血清ALT、AST活性和MDA含量，升高SOD、GSH-Px活性。结论珍珠梅水提物对CCl4大鼠急性肝损伤有保护作用。     

Ketoprofen glucuronidation and bile excretion in carbon tetrachloride and alpha-naphthylisothiocyanate induced hepatic injury rats

A pharmacokinetic study was carried out in rats to investigate the effects of experimental hepatic injury on the liver glucuronidation and bile excretion of ketoprofen (KP) and its glucuronides (KPGs). In vivo, KP (20 mg/kg b.w.) was intravenously administered to carbon tetrachloride (CCl₄) or alpha-naphthylisothiocyanate (ANIT) induced hepatic injury male rats. Concentrations of KP and its glucuronides (S-KPG and R-KPG) in plasma and bile were determined by RP-HPLC. It was observed that there was significant difference in the accumulative bile excretion of KPGs between the CCl₄ intoxicated rats and the normal rats (54 ± 18.3% versus 90 ± 6.9%), while it was extremely inhibited in ANIT intoxicated rats (2.0 ± 3.1% versus 90 ± 6.9%). As the result of reduction of KPGs excreted in bile, the area under the curve (AUC_(0–∞)) of KP and KPGs were higher in blood in CCl₄ and ANIT hepatic injury rats than those of the normal rats. Specifically, ANIT caused approximately 10-fold elevation of AUC_(0–∞) of plasma S-KPG. In microsomal incubations experiment, the glucuronyltransferase activity was impaired in CCl₄ and ANIT intoxicated rats. It suggested that the glucuronyltransferase activity was impaired in CCl₄ and ANIT intoxicated rats, while the bile excretion function was suppressed extremely in ANIT intoxicated rats.     

汉防已甲素对四氧化碳损伤大鼠肝的保护作用

本研究发现,汉防已甲素一次性预处理能使大鼠肝脏对毒性物质的损伤产生保护作用。用四氯化碳造成大鼠急性肝损伤模型,若预先2小时腹腔注射汉防已甲素(50mg/kg),则血清谷丙转氨酶、胆红素及死亡率都显著降低,肝组织学检查也显示损伤程度明显减轻。     

Blood coagulation variations induced by carbon tetrachloride inhalation in Wistar rats

Research into the development of chronic hepatic failure induced by CCl4 inhalation and the effect of this damage on blood coagulation was performed on Wistar rats. Exposure to CCl4 (325 ppm) consisted of the administration of 22, 26, 29, 31, 34, 39, 40, 45, and 49 doses, respectively. To determine and evaluate the nature and degree of CCl4-induced lesions at different stages of the treatment, histological alterations in liver samples were evaluated. Fatty infiltration in the centrilobular parenchymal cells observed after administration of the first doses was seen to spread toward mid- and peripheral zones of the lobules at the highest doses, accompanied by necrosis and nonelastic fibrosis. A causal relationship between liver failure and decrease in plasma fibrinogen levels was not observed, even though CCl4 does reduce protein synthesis. A lack of correlation between changes in reptilase time and quantitative variations in fibrinogen was seen. This finding was confirmed by observations of qualitative modifications in the fibrinogen caused by CCl4 inhalation, such as an increase in sialic acid content, which has been previously described. Activated partial thromboplastin time seems to be a good marker for benign liver damage in carbon tetrachloride intoxication. Nevertheless, prothrombin time does reliably reflect the degree of hepatic degeneration. These results suggest that prothrombin time may be considered a valuable prognostic index.     

Protective effects of various methanol extracts of crude drugs on experimental hepatic injury induced by carbon tetrachloride in rats

The protective effects of 67 methanol extracts of crude drugs on rat hepatic injury by carbon tetrachloride (CC14) were examined. In terms of the release of intrahepatic enzymes and bilirubin into the blood, 11 methanol extracts decreased these factors significantly. Among them methanol extracts of Caryophylli Flos, Angelicae Dahuricae Radix, Polygoni Avicularis Herba, Myricae Cortex and Forsythiae Fructus were newly found to have protective effects against acute hepatic injury induced by CCl4. And then these 11 extracts which protected hepatic injury by CCl4 were investigated for their membrane stabilizing and inhibitory effects of lipid peroxidation. The extract of Bupleuri Radix only decreased the hemolysis induced by hypotonic pressure. Nine kinds of extracts without those of Desmodii Herba and Bupleuri Radix suppressed the lipid peroxidation induced by CCl4 in rat hepatic microsomes. In addition, Scutellariae Radix, Caryophylli Flos and Myricae Cortex were shown to have inhibitory effects of non-enzymatic lipid peroxidation in rat hepatic mitochondria. This study reports that the methanol extracts of Caryophylli Flos, Angelicae Dahuricae Radix, Polygoni Avicularis Herba, Myricae Cortex and Forsythiae Fructus protect the hepatic injury by CC14 and these protective effects are connected with the inhibitory effects of the lipid peroxidation in hepatic microsomes.     

Hepatoprotective effects of phloridzin on hepatic fibrosis induced by carbon tetrachloride against oxidative stress-triggered damage and fibrosis in rats

The present study was to study the hepatoprotective effects of phloridzin (PHL) on hepatic fibrosis induced by carbon tetrachloride (CCl?) in rats, on the basis of this investigation, the possible mechanism of PHL was elucidated. Male Sprague Dawley (SD) rats were randomly divided into six groups: control, model, PHL-L, PHL-M, PHL-H and colchine. All rats except control group were intraperitoneally injected with CCl?, and control rats were injected with olive oil, twice a week for eight weeks. At the same time, the rats were orally given homologue drugs once a day, respectively. Hepatoprotective effects of PHL were evaluated by liver weight indexes, biochemical values, total antioxidant capacity and total-superoxide dismutase, histopathological observations, hepatic fibrosis, and the hepatic fibrosis relative gene and protein expressions. PHL significantly improved hepatic function; remarkably decreased serum hyaluronic acid (HA), transforming growth factor-β1 (TGF-β1), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and liver tissues hydroxyproline, malondialdehyde (MDA) levels, increased glutathione peroxidase (GSH-Px), total-antioxygen capacity (T-AOC) and total-superoxide dismutase (T-SOD) contents of liver tissues; Real-time polymerase chain reaction (PCR) and immunohisto-chemical results showed PHL might markedly reverse the up-regulated mRNA and protein expressions of the α-smooth muscle actin (SMA), TGF-β1 and tissue inhibitor of metalloproteinase-1 (TIMP1), up-regulate the matrix metalloproteinase-1 (MMP1) mRNA and protein expressions. Histopathological observations provided supportive evidence for biochemical analyses and the hepatic fibrosis relative gene and protein expressions, and with the dose of PHL increasing, the aforesaid improvement became more and more strong. The studies demonstrated that PHL exerted beneficially hepatoprotective effects on hepatic fibrosis induced by CCl?, mainly enhancing antioxidant capacity of liver organizations, reduce the level of lipid peroxidation induced by CCl?, and protect hepatocyte membranes from damage, and alleviate hepatic fibrosis.     

麦胚黄酮对四氯化碳急性肝损伤的保护作用

麦胚黄酮是从小麦胚芽中提取的黄酮类化合物（flavonoids），现代医学和分子生物学研究显示，黄酮类化合物具有抗氧化和消除自由基等生物学作用，其降血脂、抗氧化、抗肿瘤和保肝等保健功能受到广泛关注。小麦是我国北方地区的主产粮作物，深入研究麦胚黄酮的保健作用，可为麦胚在保健食品中的开发和利用提供理论依据。本研究探讨麦胚黄酮对四氯化碳（CCl4）急性肝损伤的保护作用。     

四氯化碳诱导大鼠肝纤维化进展期和恢复期模型的建立

目的确定肝纤维化进展期和恢复期。方法采用50%四氯化碳(carbon tetrachloride,CCl4)皮下注射建立大鼠肝纤维化和自然恢复模型。检测血清中丙氨酸氨基转氨酶(alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(as-partate aminotransferase,AST)、透明质酸(hyaluronic acid,HA)、层粘连蛋白(laminin,LN)、Ⅳ-C型胶原(collagenⅣ,Ⅳ-C)和Ⅲ型前胶原(procollagenⅢ,PCⅢ)含量及肝组织羟脯氨酸(hydroxyproline,Hyp)水平;HE染色和Masson胶原染色观察肝脏病理组织学改变。结果 CCl4注射8周,大鼠肝组织己出现慢性肝炎的病理变化,注射12～16周出现了典型的从肝纤维化—肝硬化的病理改变,同时大鼠血清中ALT、AST、HA、LN、Ⅳ-C和PCⅢ含量及肝组织Hyp水平逐渐上升。而随着恢复期的延长,血清中ALT、AST、HA、LN、Ⅳ-C和PCⅢ含量及肝组织Hyp水平逐渐下降。结论成功建立CCl4诱导的大鼠自愈性肝纤维化模型,并确定进展期和恢复期。     

Oral administration of diphenyl diselenide potentiates hepatotoxicity induced by carbon tetrachloride in rats

Carbon tetrachloride (CCl4) is a model for studying free radical-induced liver injury and screening hepato-protective drugs. Numerous studies have reported the involvement of oxidative stress in CCl4-induced liver damage and the hepato-protective effects mediated by different antioxidants. The present study examined the effects of diphenyl diselenide, (PhSe)2, on hepatotoxicity induced by CCl4 in rats. To this end, male Wistar rats received (PhSe)2 by oral route at the dosage of 31.2 mg/kg for one or two days. After the second day of treatment, rats received CCl4 orally in a single dose. The liver and kidney were utilized for determination of histopathology, biochemical [aspartate (ALT) and alanine (AST) aminotransferases, alkaline phosphatase (ALP), total bilirrubin (TB) and gamaglutamyl transferase (GGT)] and toxicological parameters [thiobarbituric reactive species (TBARS) levels, catalase activity, ascorbic acid, nonprotein thiols (NPSH) and aminolevulinate dehydratase (-ALA-D) activity]. Repeated administration of (PhSe)2 caused a marked potentiation of hepatotoxicity induced by CCl4 exposure, as manifested by an increase in biochemical parameters (AST, ALT, ALP, GGT and BT) and severe alteration in histopathology. This study also demonstrated a potentiation of TBARS levels and a consequent depletion of important antioxidant defenses including catalase and ascorbic acid. Pre-treatment with a single dose of (PhSe)2 prevented the effect of strychnine, a substrate for CYPs, abolishing lethality in mice. This result indicates that (PhSe)2 prevented animal death, suggesting an activator action of (PhSe)2 in CYPs. This study clearly indicates that (PhSe)2 potentiated acute hepatic damage induced by CCl4.