β淀粉样蛋白导致的线粒体损伤研究进展

阿尔茨海默病(Alzheimer disease,AD)是老年人中最常见的神经退行性疾病之一,但目前对于AD发病机制尚不清楚．越来越多的研究表明,β淀粉样蛋白 (β-amyloid,Aβ)引起的线粒体结构异常和功能损伤在AD的发病过程中发挥重要作用． Aβ引发线粒体损伤的机制主要为诱导线粒体能量代谢中几种关键酶的活性下降、线粒体分裂/融合平衡的破坏以及线粒体通透性转换孔(mitochondrial permeability transition pore, mPTP)开放．综述了Aβ引发线粒体损伤的以上几方面机制在近年来取得的进展．     

抗菌肽CGA-N12诱导的活性氧打开热带念珠菌线粒体通透性转换孔

嗜铬粒蛋白A-N12(chromogranin A-N12,CGA-N12)是衍生自人嗜铬粒蛋白A的N-端抗念珠菌肽,由第65至76位氨基酸组成。前期研究表明,CGA-N12能够降低热带念珠菌线粒体膜电位,诱导线粒体依赖性细胞凋亡。有文献报道,线粒体通透性转换孔(mitochondrial permeability transition pore, mPTP)蛋白质复合物上的二硫键和自由巯基的氧化还原状态对mPTP开关具有调节作用。本文研究了CGA-N12对热带念珠菌细胞内活性氧(reactive oxygen species, ROS)聚集、DTT还原作用下CGA-N12对线粒体膜去极化、线粒体肿胀、Ca~(2+)泄露等的影响,以期阐明CGA-N12诱导mPTP打开的分子机制。结果发现,CGA-N12使细胞内活性氧聚集,线粒体膜电位降低,线粒体肿胀,但DTT可通过还原作用抑制CGA-N12诱导线粒体产生的上述现象。结果表明,CGA-N12通过诱导ROS维持mPTP蛋白质复合物上的二硫键和巯基的氧化状态打开mPTP,提高线粒体膜通透性,使线粒体膜电位耗散。该研究结果为阐明CGA-N12对热带念珠菌的凋亡机制提供了理论依据。     

左旋精氨酸在冠脉搭桥术中心肌保护作用研究进展

冠状动脉搭桥术(Coronary artery bypass grafting,CABG)中发生心肌缺血再灌注损伤是难以避免的,而冠状动脉内皮损伤导致一氧化氮(nitrogen monoxidum NO)合成及释放减少是导致心肌缺血/再灌注损伤(Myocardial ischemia/reperfusion injury MI/RI)的重要因素。本文通过对左旋精氨酸(left-arginine,L-Arg)与NO、MI/RI之间的联系、L-Arg对MI/RI的保护作用及其机制、L-Arg-NO的心肌保护作用与剂量之间关系以及L-Arg在CABG中的临床应用等方面的研究进行综述,阐明提供外源性L-Arg通过L-Arg-NO通路促进体内NO的合成及释放,探讨左旋精氨酸在冠脉搭桥术中心肌保护作用的可行性。     

线粒体通透性转换孔在缺血后处理中的作用和机制

心肌细胞急性缺血后,及时再灌注能够挽救缺血心肌细胞的活力、减少梗死面积、促进心肌细胞功能恢复。但是再灌注是一把“双刃剑”,它产生大量活性氧类（reactive oxygen species,ROS）和Ca2＋超载,开放线粒体通透性转换孔（mitochondrial permeability transition pore,mPTP）,使线粒体肿胀,外膜破裂导致心肌细胞坏死。mPTP是线粒体非特异性的转换孔,由电压依赖性阴离子通道（voltage-dependent anion channel,VDAC）、腺苷酸转位蛋白（adeninenucleotide translocator,ANT）和亲环蛋白D（cyclophilin D,CYPD）组成。mPTP关闭维持线粒体结构完整,是缺血心肌细胞功能恢复的先决条件。缺血后处理通过减少再灌注早期ROS大量释放和拮抗Ca^2＋超载、释放内源性介质、激活再灌注损伤补救激酶（reperfusion injury salvage kinase,RISK）、抑制mPTP开放,从而保护心肌细胞。     

miR-878靶向调控Pim1促进线粒体分裂导致心肌细胞缺氧/复氧损伤

目的 心肌缺血/再灌注（MI/R）损伤是导致急性心肌梗死患者不良心血管结局的重要原因。然而,目前对MI/R损伤的分子机制仍不明确。本文旨在确定微小RNA-878(miR-878)对MI/R损伤的影响及其分子机制。方法 在H9c2细胞中建立缺氧/复氧（H/R）模型。采用CCK-8法检测细胞活力。采用生化试剂盒检测乳酸脱氢酶（LDH）含量。流式细胞术分析细胞凋亡水平。采用免疫荧光法及激光共聚焦显微镜分析线粒体形态。采用免疫荧光法检测线粒体活性氧（mtROS）水平。使用双荧光素酶报告基因实验研究miR-878与Pim1的结合位点。RNA免疫沉淀（RIP）实验验证miR-878与Pim1的结合关系。实时荧光定量PCR(RT-qPCR)和蛋白质印迹法（Western blot）检测基因的表达水平。结果 与对照组相比,miR-878在H/R处理的H9c2细胞中表达显著升高（（1.00±0.25） vs(9.70±2.63),P<0.01）。在H/R诱导的细胞中,转染miR-878抑制剂能够显著增加细胞活力（（46.67±3.00） vs(74.62±4.08),P<0.000 1）,并...     

ELABELA促进心肌梗死运动康复机制

G蛋白偶联受体Apelin receptor (APLNR, APJ)早期配体ELABELA/Toddler/Apela (ELA)是一种肽类激素,对心血管系统早期发育必不可少。心肌梗死(myocardial infarction, MI)后,ELA表达代偿性升高,外源性ELA干预具有靶向抑制氧化应激、细胞凋亡并促进心肌新生、抵抗MI所致心衰的作用,对改善病理心脏重塑和提升心功能等效果显著。运动可促进内源性ELA发挥MI心脏的保护作用。现对ELA结合运动干预改善氧化应激引起的细胞凋亡并缓解缺血心脏功能障碍等文献进行梳理,提出运动促进MI心脏功能改善与康复的新观点,从而为MI患者临床度过急性期后进行运动康复研究提供有价值的理论依据。     

线粒体分裂蛋白抑制剂在大鼠脑缺血再灌注损伤中的作用及其机制

目的:观察线粒体分裂蛋白抑制剂在大鼠脑缺血再灌注损伤中的作用,并初步探讨其在线粒体凋亡途径中的作用机制.方法:雄性Wistar大鼠48只,体重250～300 g,随机分为三组(n=16):假手术组(Sham组)、脑缺血再灌注组(I/R组)和mdivi-1预处理组(mdivi-1组),线栓法建立大鼠大脑中动脉闭塞(MCAO)模型,缺血2小时,再灌注24小时后应用流式细胞术检测神经元凋亡;Western blot法检测Cyt C蛋白的表达;RT-PCR法检测Cyt C mRNA的表达.结果:与Sham组比较,I/R组神经细胞凋亡率与CytC蛋白以及mRNA表达水平显著升高(P＜0.01).应用mdivi-1预处理后细胞凋亡率与CytC蛋白以及mRNA表达水平明显降低(P＜0.01).结论:线粒体分裂蛋白抑制剂可以明显减轻脑缺血再灌注损伤,其作用机制可能通过阻断线粒体-细胞色素C途径来抑制细胞凋亡.     

13-甲基十四烷酸对大鼠脑皮层星形胶质细胞氧反常的影响

目的研究13-甲基十四烷酸(13-methyltetradecanoic Acid,13-MTD)对大鼠脑皮质星形胶质细胞氧反常的保护作用。方法传代培养新生SD乳鼠大脑皮质星形胶质原代细胞,以氧糖剥夺/再复氧糖(OGD/R)方法复制氧反常模型,OGD 10 h/R 24 h,于再复氧糖即刻分别给予13-MTD 20,40,80μg/m L(M20,M40,M80)干预,倒置显微镜动态观察星形胶质细胞形态,细胞免疫化学鉴定角质纤维酸性蛋白(glial fibrillary acidic protein,GFAP),MTT法检测线粒体活性,免疫组化法检测星形胶质细胞的水通道蛋白4(aquaporin 4,AQP4)蛋白表达。结果OGD 10 h/R 24 h损伤后,体外培养的SD乳鼠脑皮质星形胶质细胞出现明显损伤,线粒体活性显著下降(P0.01),星形胶质细胞膜AQP4蛋白表达量明显增加(P0.01);与模型组比较,13-MTD 20,40,80μg/m L可减少损伤,使线粒体活性上升、AQP4蛋白表达减少,以80μg/m L效果最好(P0.01)。结论 13-MTD可通过降低AQP4的表达,提高线粒体活性,减轻细胞水肿,进而保护氧反常诱导的星形胶质细胞损伤。     

锌转运体Zip2对心肌缺血再灌注小鼠心肌线粒体呼吸的调控作用

本研究旨在探讨锌转运体Zip2 (SLC39A2)在心肌缺血再灌注(ischemia/reperfusion, I/R)过程中对线粒体呼吸的调控作用及其机制。通过冠状动脉左前降支结扎建立小鼠在体心肌I/R损伤模型,用电感耦合离子发射光谱仪(inductively coupled plasma-optical emission spectrometer, ICP-OES)测量心肌组织的锌含量,用高分辨呼吸测定系统(Oxygraph-2K)检测小鼠心肌线粒体呼吸功能和氧化磷酸化水平,采用Western blot技术检测小鼠心肌组织STAT3和ERK的磷酸化水平。结果显示:(1)与假手术组相比,野生型小鼠I/R心肌组织的锌含量明显降低,Zip2基因敲除小鼠I/R心肌组织的锌含量进一步降低;(2)与野生对照组相比,Zip2基因敲除组小鼠心肌线粒体呼吸控制率(respiratory control ratio, RCR)和氧化磷酸化水平降低,I/R后上述指标进一步降低;(3)与野生对照组相比,I/R后Zip2基因敲除组小鼠心肌组织STAT3 (Ser~(727))和ERK的蛋白磷酸化水平均明显降低;(4)与空载体感染组相比,I/R后STAT3感染组心肌线粒体呼吸功能明显提高,而STAT3负突变体感染组心肌线粒体呼吸功能则降低。STAT3过表达可逆转Zip2基因敲除对线粒体呼吸的抑制作用。以上结果提示,心肌I/R时Zip2通过STAT3来调控线粒体呼吸,其机制可能与STAT3 (Ser~(727))的磷酸化有关,这可能是Zip2保护心肌的分子机制之一。     

调控线粒体通透转运孔道对人肝癌耐药细胞SK-Hep1/CDDP多药耐药的影响

采用大剂量冲击、间歇诱导法获得人肝癌顺铂(cisplatin,CDDP)多药耐药细胞系SK-Hep1/CDDP。利用线粒体通透转运孔道(mitochondrial permeability transition pore,mPTP)开放剂苍术苷(atractyloside,ATR)和抑制剂环孢素A(cyclosporin,CsA)分别干预SK-Hep1和SK-Hep1/CDDP细胞;免疫印迹法检测多药耐药基因Mdr-1和Bax表达水平;采用Annexin V/PI双标记法检测细胞凋亡率;采用荧光探针JC-1检测线粒体膜电位△Ψm的变化。探讨调控线粒体mPTP对人肝癌耐药细胞SK-Hep1/CDDP多药耐药的影响。结果提示,ATR可促进mPTP开放,加速△Ψm下降,同时降低Bax活性,增加SK-Hep1/CDDP细胞凋亡;CsA抑制mPTP开放,可减轻并延迟线粒体膜电位下降,使多药耐药细胞SK-Hep1/CDDP对CDDP诱导凋亡的耐受能力提高,同时增加Bax活性。但mPTP活性的变化对细胞Mdr-1蛋白表达水平无影响。mPTP的激活可能成为增加肿瘤细胞对化疗药物敏感性及逆转肿瘤细胞多药耐药的新方法。     

Recent advances in the study of Kaposi's sarcoma-associated herpesvirus replication and pathogenesis

It has now been over twenty years since a novel herpesviral genome was identified in Kaposi's sarcoma biopsies. Since then, the cumulative research effort by molecular biologists, virologists, clinicians, and epidemiologists alike has led to the extensive characterization of this tumor virus, Kaposi's sarcoma-associated herpesvirus(KSHV; also known as human herpesvirus 8(HHV-8)), and its associated diseases. Here we review the current knowledge of KSHV biology and pathogenesis, with a particular emphasis on new and exciting advances in the field of epigenetics. We also discuss the development and practicality of various cell culture and animal model systems to study KSHV replication and pathogenesis.     

The structure, reproduction and taxonomy of Vidalia and Osmundaria (Rhodophyta, Rhodomelaceae)

Comprises species occurring mostly in subtidal habitats in tropical, subtropical and warm-temperate areas of the world. An analysis of the type species, V. spiralis (Sonder) Lamouroux ex J. Agardh, a species from Australia, establishes basic characters for distinguishing species in the genus. These characters are (1) branching patterns of thalli, (2) flat blades that may be spiralled on their axis, (3) width of the blade, (4) primary or secondary derivation of sterile and fertile branchlets and (5) position of sterile and fertile branchlets on the thalli. Application of the latter two characters provides an important basic method for separation of species into three major groups. Osmundaria , a genus known only in southern Australia, was studied in relation to Vidalia , and its separation from the Vidalia assemblage is not accepted. Species of Vidalia therefore are transferred to the older genus name, Osmundaria. Two new species, Osmundaria papenfussii and Osmundaria oliveae are described from Natal. Confusion in the usage of the epithet, Vidalia fimbriala Brown ex Turner has been clarified, and Vidalia gregaria Falkenberg, described as an epiphyte on Osmundaria pro/ifera Lamouroux, is revealed to be young branches of the host, Osmundaria prolifera.     

New or rare chromosome counts in Artemisia L. (Asteraceae, Anthemideae) and related genera from Kazakhstan

Fifteen chromosome counts of six Artemisia taxa and one species of each of the genera Brachanthemum, Hippolytia, Kaschgaria, Lepidolopsis and Turaniphytum are reported from Kazakhstan. Three of them are new reports, two are not consistent with previous counts and the remainder are confirmations of very scarce (one to four) earlier records. All the populations studied have the same basic chromosome number, x = 9, with ploidy levels ranging from 2x to 6x. Some correlations between ploidy level, morphological characters and distribution are noted.     

肝癌中HBV和HCV基因和抗原的分布及意义

采用原位分子杂交方法检测HCV RNA及HBV X基因;采用免疫组织化学方法研究HCV核心抗原,非结构区C33c抗原及HBxAg在肝细胞肝癌中的定位及分布.结果表明(1)HCV RNA、HBV X基因在肝细胞肝癌组织检出率分别为40%(55/136)和82%(112/136).HCV RNA定位于癌细胞的胞浆内,阳性细胞呈散在、灶状及弥漫分布三种形式;HBV X基因在肝癌细胞中的分布呈胞浆型、核型及核浆型,阳性细胞也呈上述三种分布形式;(2)HCV C33c抗原、核心抗原在肝细胞肝癌中的阳性率为81%(133/164)及86%(141/164).C33c抗原定位于癌细胞及肝细胞的胞浆内;核心抗原既定位于癌细胞核中,又可定位于胞浆中.C33c抗原阳性细胞以灶状分布为主;而核心抗原阳性细     

Selection with two alleles and complete dominance

For a plant selection model with frequency-independent viabilities, fertilities and selfing rates, it is shown that apart from global fixation, for certain parameter combinations a protected polymorphism and facultative fixation (either allele may become fixed according to initial frequencies) may both occur. Facultative fixation requires different selling rates for the dominant and recessive type. Protection of the polymorphism requires resource allocation for male and female function. In this connection the problem of purely genetically caused population extinction is discussed.
For general frequency dependence and regular segregation, the chances for establishment of a completely recessive gene are compared to those of a completely dominant gene. It is proven that the process of establishment of the recessive gene, despite a fitness advantage, may be considerably endangered by drift effects if random mating prevails. The recessive gene may reach the same effectivity in establishment as a dominant gene, only if the recessive homozygote mates exclusively with its own type during the period of establishment.