Oxidative stress and inflammation: liver responses and adaptations to acute and regular exercise

The liver is remarkably important during exercise outcomes due to its contribution to detoxification, synthesis, and release of biomolecules, and energy supply to the exercising muscles. Recently, liver has been also shown to play an important role in redox status and inflammatory modulation during exercise. However, while several studies have described the adaptations of skeletal muscles to acute and chronic exercise, hepatic changes are still scarcely investigated. Indeed, acute intense exercise challenges the liver with increased reactive oxygen species (ROS) and inflammation onset, whereas regular training induces hepatic antioxidant and anti-inflammatory improvements. Acute and regular exercise protocols in combination with antioxidant and anti-inflammatory supplementation have been also tested to verify hepatic adaptations to exercise. Although positive results have been reported in some acute models, several studies have shown an increased exercise-related stress upon liver. A similar trend has been observed during training: while synergistic effects of training and antioxidant/anti-inflammatory supplementations have been occasionally found, others reported a blunting of relevant adaptations to exercise, following the patterns described in skeletal muscles. This review discusses current data regarding liver responses and adaptation to acute and regular exercise protocols alone or combined with antioxidant and anti-inflammatory supplementation. The understanding of the mechanisms behind these modulations is of interest for both exercise-related health and performance outcomes.     

多氯联苯对鸡胚的毒性作用

The toxic effects of polychlorinated biphenlys (PCB) on embryonic chickens, especially on liver morphology, were studied. PCB (Aroclor 1 254) was injected into yolk of Hyline fertilized eggs, with doses of 0, 1, 10 and 100 μg/egg, respectively. The survival rate of chicken embryos in each PCB treatment group was significantly lower than that of the control group. The hatching rate of 1 μg/egg group was only 40%. Subcutaneous edema and hydrocephally were found in dead embryos and newly hatched chicks of all treatment groups. Livers of newly hatched chickens were removed for examination of histological structures. After PCB treatment, severe liver injury was apparent. The hepatic structures were damaged and steatosis was observed, together with necrosis and cell vacuolation and pyknosis. There were more Kupffers cells in the hepatic sinusoid. No PAS positive staining was found in the hepatic cytoplasm, indicating that glycogen was exhausted in the hepatic cells. The higher death rate in PCB treated groups may be related to glycogen exhaustion. These findings indicate that PCBs reduced the hatching rate by causing severe subcutaneous edema and liver injury in chicken embryos.     

啤酒对肝影响的组织化学及酶组织化学研究

啤酒为营养丰富的低度酒精饮料。目的　探讨啤酒对肝功能的影响。方法　以小白鼠作为实验对象 ,用 2 0只刚断乳昆明种 (清洁级 )小鼠随机分为两组 ,A组 (10只 )饲以标准饲料 ,强制以啤酒为饮料。B组 (10只 )饲以标准饲料 ,自由饮清水。经 2周喂养后处死 ,取小鼠肝右叶作AcP、LDH、ChE、ATPase、SDH、PAS组织化学及酶组织化学检测。结果　 (1)A、B两组未见肝细胞变性。 (2 )A、B两组AcP为阳性 (+) ,LDH为阳性 (+)。 (3)A、B两组ChE为中等阳性 ( ) ,ATPase为阳性 (+)。 (4)A组SDH为阳性 (+) ,PAS为中等阳性 ( )。B组SDH为中等阳性( ) ,PAS为强阳性 ( )。将A、B两组PAS、SDH标本各随机抽五张 ,经IBAS图像分析系统作定量测定 (P <0 0 5 ,即抽样误差小于 5 % ,有统计学意义 )。A、B组小鼠肝均无明显组织学损害。A、B组小鼠肝蛋白质及糖原合成、胆汁分泌功能未受影响。结论　长期饮用啤酒对小鼠肝的组织结构、肝合成、分泌及代谢功能未产生明显的损害及影响。     

天然配比油对家兔肝组织中脂肪酸的影响

目的　研究天然配比油对家兔肝组织中脂肪酸的影响。方法　用GC法测定 5 0只家兔喂天然配比油 90d肝组织脂肪酸组分和含量的变化。结果　猪油对照组中 14∶0、18∶1和MUFA明显增高 ;三个配比油组α18∶3水平明显增高 ,14∶0明显降低 ,配 1组的α18∶3含量最高 ,配 2和配 3组的γ18∶3和 18∶2含量明显增高、18∶1和MU FA无明显变化。结论　补充三种配比油均可提高体内n3系多烯脂酸水平 ;配比 2和配比 3油还可提高n6 系多烯脂酸质量、抑制 18∶1升高 ,治疗高脂血症效果较好     

苯并（a）芘对大弹涂鱼肝细胞超微结构的影响

在实验生态条件下,研究不同浓度苯并(a)芘(BaP)暴露下大弹涂鱼肝脏细胞超微结构的变化。结果表明,暴露于低浓度(0．5mg·L^-1)BaP 7d,大弹涂鱼肝脏细胞内的细胞器受到不同程度的损伤,其中线粒体和内质网是受BaP暴露影响最明显的细胞器,细胞核也受到不同程度的影响,细胞质中脂滴也增加;而暴露于高浓度(5mg·L^-1)BaP 2h,不仅是线粒体和内质网,几乎所有细胞器都受到严重影响,细胞器严重退化,细胞结构遭到严重破坏。研究结果证实,BaP可对大弹涂鱼肝细胞内多种细胞器造成损伤,并且BaP浓度越高,损伤程度越严重。     

大鼠短间隔连续部分肝切除上调表达基因的克隆与分析 *

以短间隔连续部分肝切除112h为试验方,以0h对照为驱动方,应用抑制性消减杂交技术构建了高效率的正向消减cDNA文库,从中随机挑取的50个克隆中有45个包含了100～350bp插入片段,对这些片段进行测序后经GenBank blast同源性检索,表明8个片段均为未知新序列。大鼠短间隔连续部分肝切除后肝再生cDNA正向消减文库的建立和未知的上调表达基因片段的克隆为研究肝再生的分子机理奠定了基础。     

人肝癌细胞基因组中HBV DNA的整合与c-fos、p53基因表达之间的关系

为了探讨HBVDNA、c-fos和p53在肝癌发生中的作用及其关系。利用PCR技术和免疫组化ABC法,检测了肝癌基因组中HBVDNA的整合、c-fos和突变p53的表达。HBVDNA整合率为67%,C-FOS蛋白阳性率为67%,突变P53蛋白阳性率为58%。HBVDNA整合与c-fos激活、p53突变有显著的一致性(P＞0.05;P＞0.05),c-fos激活与p53突变之间呈负相关,但无显著意义(r=-0.2816,P＞0.05)。HBVDNA的整合可能引起c-fos的激活和/或p53的突变,从而导致肝癌的发生。     

不同发育阶段尖头斜齿鲨肝油脂酸组成的变化

采用气相色谱仪分析测定了不同发育阶段尖头斜齿鲨肝油的脂肪酸组成与含量。在尖头斜齿鲨肝油总脂肪酸组成中 ,饱和脂肪酸占 15 3%～ 34 6 % ,单不饱和脂肪酸占 13 8%～ 2 5 6 % ,多不饱和脂肪酸 (PUFA)占 38 8%～ 6 8 1%。其中 ,最主要的脂肪酸为 16 :0 ,18:0 ,18:1ω9,2 0 :4ω6和 2 2 :6ω3。尖头斜齿鲨肝油脂肪酸组成与个体的发育状况关系密切。雄性尖头斜齿鲨 ,胚胎阶段肝油的脂肪酸主要由16 :0、 16 :1和 18:1(ω9+ω7)组成 ,2 2 :6ω3的含量很低 (3 8± 1 34 ,n =3) ;雄性幼鱼肝油 2 2 :6ω3的含量较胚胎阶段有了显著的提高 (2 7 1± 2 47,n =3) (P <0 0 5 ) ;性成熟个体肝油 2 2 :6ω3的含量达到最高值 (5 1 0± 7 42 ,n =5 ) ,退化期 2 2 :6ω3的含量明显降低 (34 4± 2 40 ,n =3)。雌性尖头斜齿鲨肝油 2 2 :6ω3的含量随着性腺的发育而逐渐增加 ,妊娠早期达到最高值 (49 7± 4 0 4,n =5 ) ,显著高于未成熟期个体 (2 5 7± 0 6 4,n =3)和卵巢发育期个体 (33 3± 3 46 ,n =4) ,妊娠结束期肝油 2 2 :6ω3的含量显著下降 (2 5 6± 8 0 8,n =3) ,提示 2 2 :6ω3在尖头斜齿鲨胚胎的生长发育中可能起了重要作用。     

Molecular therapy and prevention of liver diseases

Molecular analyses have become an integral part of biomedical research as well as clinical medicine. The definition of the genetic basis of many human diseases has led to a better understanding of their pathogenesis and has in addition offered new perspectives for their diagnosis, therapy and prevention. Genetically, human diseases can be classified as hereditary monogenic, acquired monogenic and polygenic diseases. Based on this classification, gene therapy is based on six concepts: (1) gene repair, (2) gene substitution, (3) cell therapy, (4) block of gene expression or function, (5) DNA vaccination and (6) gene augmentation. While major advances have been made in all areas of gene therapy during the last years, various delivery, targeting and safety issues need to be addressed before these strategies will enter clinical practice. Nevertheless, gene therapy will eventually become part of the management of patients with various liver diseases, complementing or replacing existing therapeutic and preventive strategies.     

肝靶向动物模型研究与展望

肝癌动物模型是抗肝癌药物实验及肝靶向给药系统验证的重要方法和手段。本文对用于研究肝靶向制剂的动物模型的种类、特征、不足及应用进行了研究论述,提出了目前较适于应用的模型,应用肝癌动物模型可以提供与肝癌病人相似的肝癌生物学特性,也为肝靶向给药制剂药代动力学指标的可靠性提供了保障。