Interaction of BW755C,a potent inhibitor of lipoxygenase and cyclo-oxygenase,with mitochondrial cytochrome oxidase

Summary The interaction between BW755C (3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline), a potent inhibitor of both lipoxygenase and cyclo-oxygenase, and respiratory chain in mitochondria and electron transport particles (ETP) from rat livers was examined. BW755C accelerated the oxygen uptake by mitochondria without the addition of substrate for the respiratory chain. Spectrophotometric study revealed that BW755C was quickly oxidized by cytochrome oxidase in mitochondria to a compound possessing an absorption maximum at 524 nm. p-Phenylenediamine (p-diaminobenzene, PPDA), which, like BW755C, serves as an electron donor to cytoschrome oxidase, was shown to inhibit the generation of active oxygen in macrophages; the inhibition was stronger than that of BW755C. These results strongly suggest that the oxidative conversion of BW755C by mitochondrial cytochrome oxidase is associated with its potentially inhibitory action on the active oxygen-generating system in phagocytes.The authors are indebted to Dr M. Hori, Gifu College of Pharmacy and to Dr Y. Orii, Kyoto University for their kind supplies of BW755C and pure cytochrome oxidase, respectively.     

软骨细胞发生和分化基因与大鼠肝再生的相关性

肝脏由多种细胞构成,肝再生与细胞分化密切相关,细胞分化受基因转录水平调控.为在基因转录水平了解软骨细胞的发生和分化相关基因在大鼠肝再生中作用,通过搜集网站资料和查阅相关论文等方法获得参与软骨细胞发生和分化的基因,用Rat Genome 230 2.0芯片检测它们在大鼠肝再生(liver regeneration,LR)中表达情况,用比较真、假手术中基因表达差异确定肝再生相关基因.初步证实上述基因中23个基因与肝再生相关.肝再生启动(PH后0.5～4 h)、G0/G1过渡(PH后4～6 h)、细胞增殖(PH后6～66 h)、细胞分化和组织结构功能重建(PH后72～168 h)等四个阶段起始表达的基因数为15、4、8和0;基因的总表达次数为15、10、22和17.表明相关基因主要在肝再生启动阶段起始表达,在不同阶段发挥作用.它们共表达上调100次、下调77次,分为17种表达方式,表明肝再生中软骨细胞发生和分化相关基因活动多样和复杂.根据本文研究结果推测,上述基因不仅调节软骨细胞发生和分化,而且参与肝再生的生理生化活动.     

肾草酸钙结石大鼠肾组织中Claudin-14的表达变化及意义

为构建大鼠肾草酸钙结石模型,从基因和蛋白水平初步探讨紧密连接蛋白-14(Claudin-14)在肾草酸钙结石大鼠肾组织中的表达变化及意义。采用30只雄性S-D大鼠随机分为对照组(n=15)和结石组(n=15),采用乙二醇和氯化铵灌胃诱导制作大鼠肾草酸钙结石模型。分别采用RT-PCR检测Claudin-14 mRNA表达;Western-Blotting检测Claudin-14蛋白表达;全自动生化分析仪检测各组大鼠24 h尿钙排泄。结果显示:光镜下结石组有大量结石结晶形成,且24h尿钙较对照组显著升高(P0.01),Claudin-14 mRNA表达较对照组显著升高(P0.01);Claudin-14蛋白在结石组高表达,在对照组未见表达;相关性分析发现结石组Claudin-14蛋白表达与24 h尿钙排泄呈显著正相关。由此可知,Claudin-14在肾草酸钙结石大鼠肾组织中高表达,可能是肾小管内尿钙增高,结石形成的机制之一。     

极化液对大鼠不同血糖浓度下心肌缺血再灌注的影响

目的:探讨不同血糖浓度下大鼠心肌缺血再灌注(MI/R)心肌损伤的程度及明确极化液(GIK)对高血糖心肌MI/R的保护作用.方法:将12只健康SD大鼠,随机分为4组,每组3只,即对照组、GIK组、高血糖组、GIK+高血糖组.每组大鼠结扎左冠状动脉前降支30 min,再灌注120 min.采用氯化三苯基四氮唑(TTC)染色法检测大鼠缺血再灌注心肌的心肌梗死面积.动态观察Ⅱ导联心电图QRS波、T波、ST段和心率变化.结果:TTC染色显示每组大鼠心肌都有梗死,心肌梗死面积高血糖组>GIK+高血糖组>对照组>GIK组;心电图显示高血糖大鼠心肌缺血期ST段明显抬高,再灌注后实验动物出现心律失常.GIK对正常血糖大鼠MI/R具有明显保护作用.结论:GIK对高血糖大鼠心肌缺血再灌注损伤保护作用有限,而对正常血糖大鼠MI/R损伤有较好的保护作用.