血清生物标志物水平在妊娠期肝内胆汁淤积症诊断中的临床意义

目的 探讨生物标志物水平在妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)诊断中的临床意义.方法 测定86例ICP产妇(轻度和重度各43例)和86位正常孕妇的血清总胆汁酸(total bile acid,TBA)、雌三醇(estriol,E3)、肿瘤坏死因子-d(tumor necrosis factor-α,TNF-α)、高敏C-反应蛋白(high sensitive C-reactive protein,hs-CRP)和降钙素原(procalcitonin,PCT)水平,并进行对比性分析和围生期结局比较.对血清TBA与E3、TNF-α、hs-CRP和PCT水平进行Pearson相关性分析.结果 86例ICP产妇的血清TBA、E3、TNF-α、hs-CRP和PCT水平较之86位正常孕妇明显增高(P均＜0.01),并随ICP产妇的严重程度而增高.血清TBA水平与E3、TNF-α、hs-CRP、PCT水平呈正相关(r分别为0.846、0.530、0.863和0.781,P均＜0.05).在围生期结局比较中,86例ICP产妇较之正常孕妇早产、羊水胎粪污染、新生儿窒息和胎儿窘迫的发生率明显增高(P＜0.01).结论 血清E3、TNF-α、hs-CRP、PCT与TBA水平呈正相关,并与妊娠期肝内胆汁淤积症严重程度及不良妊娠结局有关,上述血清学标志可作为疾病诊断、严重程度判断的重要指标,并提示上述指标可能参与ICP的发生和发展.     

Sex-dependent compensated oxidative stress in the mouse liver upon deletion of catechol O-methyltransferase

Catechol-O-methyl transferase (COMT) methylates catechols, such as l-dopa and dopamine, and COMT deficient mice show dramatic shifts in the metabolite levels of catechols. Increase in catechol metabolite levels can, in principle, lead to oxidative stress but no indices of oxidative stress have been reported in COMT-knockout (KO) mice [Forsberg MM, Juvonen RO, Helisalmi P, Leppanen J, Gogos JA, Karayiorgou M, et al. Lack of increased oxidative stress in catechol-O-methyltransferase (COMT)-deficient mice. Naunyn Schmiedebergs Arch Pharmacol 2004;370:279-89.]. Here we perform a proteomic based analysis of the livers of COMT-KO mice in search for potential compensatory mechanisms developed to cope with the effects of disrupted catechol metabolism. We found sex specific changes in proteins connected to stress response. Our results show that alterations in protein levels contribute to the homeostatic regulation in the liver of COMT deficient mice.     

Protective effects of silica hydride against carbon tetrachloride-induced hepatotoxicity in mice

The protective effects of MegaHydrate™ silica hydride against liver damage were evaluated by its attenuation of carbon tetrachloride (CCl₄)-induced hepatotoxicity in mice. Male ICR mice were orally treated with silica hydride (104, 208 and 520 mg/kg) or silymarin (200 mg/kg) daily, with administration of CCl₄ (1 mL/kg, 20% CCl4 in olive oil) twice a week for eight weeks. The results showed that oral administration of silica hydride significantly reduced the elevated serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride (TG), and cholesterol and the level of malondialdehyde (MDA) in the liver that were induced by CCl₄ in mice. Moreover, the silica-hydride treatment was also found to significantly increase the activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-Px), as well as increase the GSH content, in the liver. Liver histopathology also showed that silica hydride reduced the incidence of liver lesions induced by CCl₄. The results suggest that silica hydride exhibits potent hepatoprotective effects on CCl₄-induced liver damage in mice, likely due to both the increase of antioxidant-defense system activity and the inhibition of lipid peroxidation.     

黄药子醇提物致大鼠肝损伤血清总胆汁酸早期变化研究

目的 :探讨血清总胆汁酸(TBA)作为黄药子醇提物致肝损伤早期敏感标志物的可能性。方法:取Wistar大鼠随机分为对照组和黄药子醇提物组(以下简称黄药子组),黄药子组每天灌胃给予醇提物5 g/kg,对照组灌服蒸馏水,于给药后1 d、7 d、16 d分批处理动物。乌拉坦麻醉动物,取血,测定常规血液生化指标-丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TB)、碱性磷酸酶(ALP)、总蛋白(TP)、白蛋白(ALB)和文献报道的血清早期敏感指标-总胆汁酸(TBA)的水平,取肝,称重,计算肝脏指数并进行HE染色观察肝组织病理形态学变化。结果:与同时间点对照组相比,黄药子组常规生化指标AST和TB的变化较为明显,AST于给药1d～7d升高(P<0.01),TB于给药7 d有升高的趋势(P>0.05),16 d升高(P<0.01);肝脏指数于给药7d～16d升高(P<0.05或0.01),肝组织病理形态学检查显示16 d开始出现细胞肿大和单细胞坏死。血清早期敏感指标TBA于给药1d、7d、16d升高(P<0.05或0.01),与AST比较,TBA表现出良好的时效关系,较TB变化更早;与同时间点对照组相比,TBA数值的变化倍数均高于AST和TB。结论:TBA可作为黄药子致肝损伤的早期敏感生物标志物之一。     

血清胆碱酯酶及联合测定对肝硬化患者的临床价值

目的探讨血清胆碱酯酶及联合测定在肝硬化患者child-pugh分级中的临床价值。方法分析67例肝硬化患者和60例健康人员的血清CHE及白蛋白（ALB）γ-谷氨酰转移酶（GGT）、总胆汁酸（TBA）水平及凝血功能等测定结果。结果肝硬化组与对照组相比,CHE、ALB血清含量下降,GGT、TBA血清含量提高;在肝功能分级中各项指标也有意义。结论 CHE是诊断和鉴别诊断肝硬化的敏感特异血清学指标,CHE及联合测定有助于准确评估肝功能的损害程度和预后,对肝硬化的病情变化有一定的临床价值。     

慢性肝炎血清总胆汁酸水平与肝组织炎症程度的关系

目的：探讨血清总胆汁酸（TBA）水平与肝实质病变的关系。方法：对102例慢性肝炎患者作肝活检,观察肝组织病理分级分期及划分慢性肝炎病理程度,并检测血清TBA、白蛋白（ALB）、总胆红素（TBil）、谷丙转氨酶（ALT）。结果：肝组织炎症轻度（G1-2,S0-2）、中度（G3,S1-3）、重度（G4,S4）的TBA水平（x±s）分别为（16.74±13.34）μmol/L、（72.25±68.49）μmol/L和（186.34±96.18）μmol/L,呈重度〉中度〉轻度状态。轻度组和中度组与重度组比较均为P〈0.01。结论：慢性肝炎血清TBA水平与肝组织炎症程度具有良好正比关系,对判断肝实质病变具有重要临床价值。     

In vivo antioxidative activity of a quantified Pueraria lobata root extract

Aim of the study

Oxidative stress has been associated with many pathological disorders such as atherosclerosis, diabetes and cancer. Supplementation with exogenous antioxidants, including phenolic compounds from plant sources, may help to restore the pro-oxidative/antioxidative balance. To take into account effects of absorption, metabolisation, plasma protein binding, distribution, and elimination, antioxidative research should not be limited to in vitro assays but be extended to in vivo models.

Materials and methods

In the present work a quantified 50% EtOH root extract of Pueraria lobata (Willd.) Ohwi (Fabaceae) was selected to determine its in vivo antioxidative activity in a diabetic rat model, where diabetes and the accompanying oxidative stress were induced by intraperitoneal administration of streptozotocin. This root extract was found to contain 10.42 ± 0.15% puerarin as the main constituent and smaller amounts of the related isoflavonoids 3′-hydroxypuerarin, 3′-methoxypuerarin, 6″-xylosylpuerarin, daidzin, genistin, daidzein and genistein, as determined by a validated HPLC method. This extract was administered orally at a daily dose of 500 mg/kg root extract, corresponding to 50 mg/kg puerarin, during 3 weeks. In addition the effect on the plasma concentration of some fat-soluble antioxidants (co-enzyme Q₉, α- and γ-tocopherol) was evaluated.

Results and conclusions

The level of malondialdehyde (MDA) in plasma, used as a marker of oxidative damage to lipids, was reduced to the same level as in healthy control animals, and as in the positive control group treated daily with 50 mg/kg α-tocopherol acetate. No obvious signs of toxicity were observed by administration of 10× the treatment dose.