聚腺苷二磷酸核糖聚合酶在休克和缺血再灌注损伤中的作用

聚腺苷二磷酸核糖聚合酶在失血性休克、内毒素性休克和感染性休克,以及机体主要脏器缺血再灌注后激活,参与休克和缺血再灌注损伤的病理过程。抑制聚腺苷二磷酸核糖聚合酶对休克和缺血再灌注损伤有良好的防治作用。     

丹参素对大鼠心肌缺血／再灌注损伤的保护作用

本实验采用Langendorff灌注模型,对心肌缺血/再灌注损伤中氧自由基清除酶系统超氧化物歧化酶(SOD)、谷胱甘肽过氧化酶(GSH-P_x)和超微结构的变化及丹参素的抗氧化效应进行了观察。随缺血时间的延长,SOD及GSH-P_x的活性逐步下降。当心肌缺血40分钟后富氧再灌注20分钟,SOD的活性仍然继续下降;GSH-P_x的活性明显低于缺血60分钟组,此时超微结构损伤最为严重。预先给丹参素及亚硒酸钠再进行缺血/再灌注,心肌SOD、GSH-P_x活性明显高于单纯缺血/再灌注时,超微结构损伤亦较轻,且丹参素的保护效果优于亚硒酸钠。     

环磷酸腺苷在心肌缺血／再灌注心律失常中的作用

本文应用放免法测定Ｗｉｓｔａｒ大鼠离体心脏缺血／再灌注期间心脏灌流液中环磷酸腺苷含量变化，并探讨其与心肌缺血／再灌注心律失常的关系，结果表明，冠脉结扎５ｍｉｎ时，ｃＡＭＰ无显著增加，同时未见心律失常，结扎１０－１５ｍｉｎ时，ｃＡＭＰ含量显著增加，并出现各类室性心律失常，再灌注１ｍｉｎ时ｃＡＭＰ较灌注前非常显著增加，而这１ｍｉｎ内，所有心脏均出现再灌注心律失常，１０ｍｉｎ后心律失常显著减少，此时ｃＡ     

心肌缺血后处理减轻大鼠缺血/再灌注心肌细胞凋亡及超微结构损伤

缺血预处理(ischemic preconditioning)是减轻缺血/再灌注损伤最有效的方法.Zhao等[1]最近提出的缺血后处理,即心肌缺血后再灌注前反复短暂开通及再闭冠脉,与缺血预处理一样可降低心肌梗死范围及心肌酶释放,但其对心肌细胞凋亡及超微结构的影响国内、外报道较少,尚未见同时从亚细胞水平及细胞凋亡改变评价的报道.     

心肌缺血再灌注损伤的发病因素

心肌缺血再灌注损伤是近年来随着临床治疗心血管疾病新技术如各种冠脉再通术、PTCA、搭桥术等的广泛应用而被重视的一种反常现象。人们观察到遭受一定时间缺血损伤的心肌组织恢复血液灌流后组织损伤反     

肝X受体通过调控GLUT-4减轻心肌缺血/再灌注损伤

 目的：探讨肝X受体（LXRs）是否通过调控葡萄糖转运蛋白4（GLUT-4）减轻大鼠离体心脏缺血/再灌注损伤。方法：应用Langendorff装置建立大鼠离体心脏缺血/再灌注损伤模型;实验分组：LXRs激动剂T0901317（0.1 μmol/L、0.5 μmol/L和10 μmol/L）预处理组、缺血预适应组、对照组和模型组;比较各组乳酸脱氢酶（LDH）和肌酸激酶（CK） 活性、心梗面积、左室舒张末压（LVEDP）、左室发展压（LVDP）、左室内压力变化速率（±dp/dt max）、冠脉流量（CF）、心肌组织GLUT-4 mRNA和细胞膜GLUT-4蛋白量。结果：模型组在缺血/再灌注后LDH、CK活性及心梗面积均增加(P<0.05),并产生血流动力学障碍(P<0.05);T0901317预处理显著降低CK和LDH活性,减小心梗面积(P<0.05),明显改善因I/R损伤引起的血流动力学障碍 (P<0.05 ),进一步增加由I/R损伤诱导的心肌细胞GLUT-4 mRNA表达及细胞膜GLUT-4蛋白表达(P<0.05)。结论：LXRs可能通过调控GLUT-4表达减轻离体灌流心脏的缺血/再灌注损伤。     

左型精氨酸减轻心肌缺血再灌注损伤的实验研究

以往实验证实，心肌缺血再灌注损伤（ｍｙｏｃａｒｄｉａｌｉｓｃｈｅｍｉａ－ｒｅｐｅｒｆｕｓｉｏｎｉｎｊｕｒｙ，ＭＩＲＩ）与内源性一氧化氮（ｎｉｔｒｉｃｏｘｉｄｅ，ＮＯ）水平下降有关。本研究观察左型精氨酸（Ｌ－ａｒｇｉｎｉｎｅ，Ｌ－Ａｒｇ）对ＭＩＲＩ时血...     

肢体缺血后处理对兔急性心肌缺血再灌注损伤的影响

目的:探讨肢体缺血后处理对兔急性心肌缺血再灌注损伤的影响及其可能机制。 方法:健康新西兰大白兔30只，随机分为3组(每组10只)：对照组(Con)、心肌缺血后处理组(MIP)和肢体缺血后处理组(LIP)。缺血前、缺血后及再灌注结束后分别测定血浆磷酸肌酸激酶(CK)活性和丙二醛(MDA)含量；实验结束后，测心肌梗死面积并检测心肌组织髓过氧化物酶(MPO)活性。 结果:MIP和LIP组心肌梗死面积均明显低于Con组(P﹤0.01)；再灌注180 min末血浆CK活性检测证实心肌梗死面积的这种差异；MIP和LIP组再灌注180 min末MDA含量明显低于Con组(P﹤0.01)；MIP和LIP组中性粒细胞在缺血心肌的聚集程度，即组织MPO活性(U/100 g)均明显轻于Con组 (P﹤0.01)。 结论:心肌缺血再灌注前肢体短暂缺血具有显著的心肌保护作用。这种远隔器官缺血后处理心脏保护作用可能与减轻活性氧的损伤及抗氧化作用加强有关。     

自噬与心肌缺血/再灌注损伤

Autophagy is a lysosome-dependent degradative pathway which is characterized by cytoplasmic vacuolization. However, it is not just a simple degradative pathway. Research shows that autophagy is related to many diseases, such as neurodegenerative disease, malignant tumor, ageing, pathogenic microorganism infection, myocardial ischemia/reperfusion injury and so on. Autophagy exactly exists in myocardial ischemia/reperfusion injury, and it becomes a new research hotspot. This review will focus on the occurrence and development of autophagy and its role, signal transduction and research status in myocardial ischemia/reperfusion injury.     

Increased poly(ADP-ribose) polymerase activity in lymphoblastoid cell lines from centenarians

 Poly(ADP-ribosyl)ation is a posttranslational modification of nuclear proteins which is catalyzed by poly(ADP-ribose) polymerase and represents an immediate response of eukaryotic cells to oxidative and other types of DNA damage. Previously a strong correlation had been detected between maximal poly(ADP-ribose) polymerase activity in permeabilized mononuclear leukocytes of various mammalian species and species-specific life span. To study a possible relation between longevity and poly(ADP-ribosyl)ation in humans we measured maximal oligonucleotide-stimulated poly(ADP-ribose) polymerase activity in permeabilized, Epstein-Barr virus transformed lymphoblastoid cell lines from a French population of 49 centenarians and 51 controls aged 20–70 years. Maximal enzyme activity was significantly higher in centenarians than in controls [median of controls: 9035 cpm/10⁶ cells (lower quartile: 6156; upper quartile: 11,410); median of centenarians: 10,380 cpm/10⁶ cells (lower quartile: 7994; upper quartile: 12,991); P=0.031 by Mann-Whitney U test]. In a subset of 16 controls and 24 centenarians, cellular poly(ADP-ribose) polymerase content was determined by quantitative western blotting, thus allowing the calculation of specific enzyme activity. The latter was significantly higher in centenarians (P=0.006), the median value for centenarians being about 1.6-fold that of controls. Specific poly(ADP-ribose) polymerase activity was a more powerful parameter for differentiating between centenarians and controls than enzyme activity relative to cell number. In addition, in a genetic association study we analyzed 437 DNA samples (239 centenarians and 198 controls) by PCR amplification of a polymorphic dinucleotide repeat located in the promoter region of the poly(ADP-ribose) polymerase gene in an attempt to detect an association between this polymorphic marker and variability of enzyme activity or human longevity. However, this genetic analysis revealed no significant enrichment of any of the alleles or genotypes identified among centenarians or controls, but its power was limited by the relatively weak hetero-zygosity of this polymorphic marker in our population (51%). Viewed together with previous results on poly(ADP-ribose) polymerase activity in various mammalian species, the present data provide further evidence for the notion that longevity is associated with a high poly(ADP-ribosyl)ation capacity. Received: 5 September 1997 / Accepted: 10 November 1997     

聚腺苷二磷酸核糖聚合酶假基因多态性分布及其与肺癌易感性的关系

目的 研究聚腺苷二磷酸核糖聚合酶假基因多态性在汉族人群中的分布，探讨该等位基因在衡量肺癌易感性方面的意义。方法 肺癌患者63例，与病例在年龄、性别等方面匹配的健康对照82名，抽提外周血白细胞基因组DNA，特定引物PCR扩增，在含溴乙锭的琼脂糖凝胶中电泳，紫外光下观测和成像。结果 病例组和对照组的基因型分布差异无显著性，B等位片段频率分别为0.095和0.116；无论是否含有B基因，吸烟都是肺癌的危险因素（P＜0．05），基因型为AA时，吸烟的比值比（odds ration,OR)是2.28，基因型为AB或BB时，其OR则达4.83；在不吸烟者中，AB或BB基因型者患肺癌的危险性并未增高（P=0.202)。结论 中国汉族人群B等位片段频率较其他民族低，是肺癌的可能易感标记，但只在吸烟者才表现出来，二者存在协同作用。     

Poly(ADP-ribose) polymerase-1 is involved in the neuronal death induced by quinolinic acid in rats

Reactive oxygen and nitrogen species formation leads to DNA damage in animals treated with quinolinic acid. Poly(ADP-ribose) polymerase-1 (PARP-1) is a protein involved in the DNA base excision repair system. Its overactivation promotes cellular energy deficit and necrosis. Here, we evaluated the effect of PJ-34, a potent inhibitor of PARP-1, on the neuronal damage induced by quinolinic acid. Animals were administered with PJ-34 (10 mg/kg, i.p.), 1 h before and 1 h after a striatal infusion of 1 μl of quinolinic acid (240 nmol). PJ-34 clearly attenuated the circling behavior produced by quinolinic acid and completely prevented the histological damage induced by the toxin. The protective effect of PJ-34 suggests that PARP-1 activation is playing an active role in the neuronal death induced by quinolinic acid.     

Poly(ADP-ribose) polymerase (PARP) and DNA-fragmentation factor (DFF45): expression and correlation in normal, hyperplastic and neoplastic endometrial tissues

This study evaluated the immunohistochemical expression of poly(ADP-ribose) polymerase (PARP) and DNA fragmentation factor 45 (DFF45) in normal endometria (NE, n=13), non-atypical (NAH, n=22) and atypical hyperplasia (AH, n=14), endometrioid carcinoma (EC, n=34), serous carcinoma (SC, n=10), and clear cell carcinoma (CCC, n=2). With regard to quantity and intensity of positively stained cells, immunostaining was scored as negative, low, and strong. Nuclear PARP immunoreactivity was found in all cases. If present, DFF45 immunoreactivity was detected predominantly in the nucleus and to some extent in the cytoplasm. PARP immunoreactivity increased significantly from NE via NAH to AH (P=0.0004), and decreased from AH to endometrial carcinomas (P=0.0054). DFF45 immunoreactivity increased significantly from NE to NAH and to AH (P=0.0009). No significant differences were calculated between AH and endometrial carcinomas (P=0.7495). FIGO stages and tumor grades could not be characterized by PARP and DFF45 immunoexpression (P=1.000 and 0.7383, as well as P=0.3034 and 0.7533, respectively). Pearson correlation revealed significant associations of PARP and DFF45 immunoscores for all diagnostic categories of NE, NAH, AH, EC, and SC/CCC. Immunoexpression of PARP and DFF45 is apparently altered in endometrial carcinomas as compared with non-neoplastic endometrial tissues, indicating impaired mechanisms of apoptosis in the former.     

Enzyme characteristics of recombinant poly(ADP-ribose) polymerases-1 of rat and human origin mirror the correlation between cellular poly(ADP-ribosyl)ation capacity and species-specific life span

Poly(ADP-ribosyl)ation is a posttranslational modification, which is involved in many cellular functions, including DNA repair and maintenance of genomic stability, and has also been implicated in cellular and organismal ageing. We have previously reported that maximum poly(ADP-ribosyl)ation capacity in mononuclear blood cells is correlated with mammalian life span. Here we show that the difference between a long-lived and a short-lived species tested (i.e. man and rat) is directly mirrored by the enzymatic parameters of recombinant poly(ADP-ribose) polymerase-1 (PARP-1), i.e. substrate affinity and reaction velocity. In addition, we have characterized two human PARP-1 alleles and assign their activity difference to their respective initial velocity and not substrate affinity.     

多聚（二磷酸腺苷-核糖）聚合酶介导过氧亚硝基阴离子致豚鼠气道反应性增高的研究

目的:探讨多聚(二磷酸腺苷-核糖)聚合酶(PARP)在ONOO^-致豚鼠气管高反应性中的作用。方法:建立离体豚鼠气管条对组胺反应的浓度反应曲线,观察PARP抑制剂3-氨基苯甲酰胺(3-AB)对过氧亚硝基阴离子(ONOO^-)诱导豚鼠气管反应性变化的影响。结果:ONOO^-(0.5 mmol/L)引起豚鼠气管上皮细胞明显受损,气管条对组胺的反应性及敏感性明显增高,3-AB(1 mmol/L或5 mmol/L)逆转了ONOO^-的上述作用;3-AB(5 mmol/L)本身对正常气管条收缩反应无明显影响。结论:PARP介导了ONOO^-所引起的气道上皮细胞的损伤和气道高反应性的形成,提示通过抑制PARP的过度活化可为防治哮喘气道高反应性提供新策略。     

多聚ADP-核糖聚合酶抑制剂对帕金森病小鼠相关脑区病理变化的影响

目的研究帕金森病(Park inson’s d isease,PD)小鼠黑质和纹状体多巴胺(dopam inergic,DA)能神经元数量和超微结构的变化及多聚ADP-核糖聚合酶(poly(ADP-ribose)polym erase,PARP)抑制剂PJ34的干预作用。方法采用1-甲基-4-苯-1,2,3,6-四氢吡啶(1-m ethyl-4-phenyl-1,2,3,6-tetrahydropyrid ine,MPTP)制备PD小鼠模型,并用PJ34进行干预,2h、24h、72h进行酪氨酸羟化酶(tyrosine hydroxylase,TH)免疫组化染色观察DA能神经元数量,透射电镜观察超微结构改变。结果与正常对照小鼠比较,PD小鼠黑质TH阳性神经元进行性减少,核膜皱缩,染色质凝聚成块并有边聚现象;纹状体TH阳性神经纤维稀疏,突触数量减少。与PD小鼠比较,PJ34干预组黑质TH阳性神经元明显增多,纹状体TH阳性神经纤维密度增加(P<0.01),细胞形态比模型组明显改善。结论PARP的活性改变在PD的发病过程中发挥重要作用,PARP抑制剂对DA能神经元有保护作用。