• 2011年第38卷第11期文章目次
    全 选
    显示方式: |
    • >干细胞专题
    • 编者按: 干细胞研究与人类健康

      2011, 38(11):981-981.

      摘要 (5789) HTML (39) PDF 0.00 Byte (4254) 评论 (0) 收藏

      摘要:干细胞作为一种具有再生各种组织器官潜能的组织细胞,在器官移植、细胞治疗、组织工程、生殖医学等多个领域的基础研究与临床应用前景广泛。干细胞研究已经成为国内外生物学研究的热点,并且是我国“十二五”期间重点支持的研究领域。为促进国家干细胞研究领域的发展,我国政府于2011年10月专门成立了国家干细胞研究指导协调委员会,以统一指导和协调我国干细胞研究领域的发展。中国科学院从2011年启动“干细胞与再生医学”先导专项,对“十二五”期间中国科学院干细胞领域的专项研究进行了重点部署。
      随着科研投入力度的加大,近年来我国干细胞研究进展迅速,许多研究成果已经走在世界前沿。本刊对干细胞领域的研究也十分关注,2009年以来共发表有关论文20余篇,涉及到干细胞分化、造血干细胞、肿瘤干细胞、神经干细胞及重编程研究等多个研究方向。为促进对该领域现状及发展的了解,本期汇集了3篇述评和1篇研究论文,作为干细胞研究专题发表,以飨读者。本专题对诱导性多能干细胞、体细胞重编程、干细胞遗传操作技术等3个方面的现状和发展进行了评述,并报道了间充质干细胞成骨分化机理方面的研究成果,反映了目前干细胞研究的一个侧面。刘光慧等主要评介了基于人多潜能干细胞的人类疾病机理与治疗研究的进展,分析了该领域研究成果为人类疾病的发病机制研究和再生医学治疗带来的革命性突破。张毅等简要概括了体细胞重编程的主要方法, 并重点评介了细胞提取物处理技术的研究进展,初步阐明该技术的原理和机制,为其应用奠定基础。孟姝总结了大鼠胚胎干细胞遗传操作技术的研究进展,基于大鼠胚胎干细胞的基因敲除模型的建立,将在揭示基因的生理功能、研究人类疾病的遗传机制以及寻找新药物靶标的过程中发挥更加重要的作用。袁军等研究发现,BMP9可通过p38激酶途径调控间充质干细胞C3H10T1/2成骨分化,进一步揭示了BMP9诱导和调控间充质干细胞成骨分化的机理。
      本刊欢迎和期待更多、更好的有关干细胞研究的来稿,以更广泛和深入地促进我国干细胞研究领域的学术交流。

    • 综述:基于人多潜能干细胞的人类疾病研究与治疗

      2011, 38(11):982-987.

      摘要 (3687) HTML (136) PDF 0.00 Byte (6305) 评论 (0) 收藏

      摘要:人多潜能干细胞(hPSC)包括人胚胎干细胞(hESC)和诱导性多潜能干细胞(hiPSC),理论上具有分化成为人类所有细胞类型的能力.基于hPSC的基因打靶技术,不但可以纠正人基因组中的遗传突变用于细胞治疗,还可以通过反向遗传学的方式向hPSC引入疾病特异的突变.将携带人类疾病遗传基因的hPSC分化为特定的细胞类型,在理论上可以在体外模拟人类疾病的发生,研究人类疾病发生的机理,并建立体外筛选平台寻找治疗性药物.基因编辑和干细胞技术的结合将为人类疾病的机制研究和再生医学治疗带来革命性的突破.

    • 综述: 细胞提取物重编程研究进展

      2011, 38(11):988-994.

      摘要 (3623) HTML (79) PDF 0.00 Byte (5216) 评论 (0) 收藏

      摘要:体细胞重编程是在特定的条件下使已分化的细胞转变成为另一种细胞.体细胞重编程的方式主要有体细胞核移植技术、细胞融合技术、细胞提取物处理技术及特定转录因子转染技术.现有研究表明,细胞提取物重编程技术在体细胞重编程中发挥着一定的作用,为此,就该技术的最新研究进展和可能机制作一综述.

    • 综述: 大鼠胚胎干细胞遗传操作技术的研究进展

      2011, 38(11):995-1000.

      摘要 (3128) HTML (4) PDF 0.00 Byte (5472) 评论 (0) 收藏

      摘要:大鼠ES细胞的成功建立使大鼠的遗传学操作成为可能,运用同源重组原理改造ES细胞的基因,为建立时空特异性的基因敲除大鼠模型提供了基础。本文主要回顾了大鼠ES细胞的建立过程,总结了大鼠ES的培养、鉴定技术,分析了各种大鼠基因敲除技术的优劣势和未来前景。在干细胞研究蓬勃发展的背景下,作为最有效地定向修饰基因的技术手段,基于大鼠ES细胞的基因敲除技术将在揭示基因的生理功能、研究人类疾病的遗传机制以及寻找新药物靶标的过程中发挥更加重要的作用。

    • 研究报告:骨形态发生蛋白9通过p38激酶途径调控间充质干细胞C3H10T1/2成骨分化

      2011, 38(11):1001-1010.

      摘要 (3699) HTML (36) PDF 0.00 Byte (4850) 评论 (0) 收藏

      摘要:前期研究发现骨形态发生蛋白9(bone morphogenetic protein 9,BMP9)具有较强的诱导间充质干细胞成骨分化的能力.为进一步揭示其诱导和调控间充质干细胞成骨分化的机理,利用BMP9重组腺病毒感染间充质干细胞C3H10T1/2,通过体外细胞实验和体内动物实验,初步分析BMP9是否可通过p38激酶途径调控间充质干细胞成骨分化.结果发现,BMP9可以通过促进p38激酶磷酸化而导致其活化,p38抑制剂SB203580可抑制由BMP9诱导的C3H10T1/2细胞的碱性磷酸酶(alkaline phosphatase,ALP)活性、骨桥蛋白(osteopontin, OPN)表达和钙盐沉积,而且利用抑制剂SB203580抑制p38激酶活性后,BMP9诱导的Smad经典途径的激活也相应受到抑制,RNA干扰导致p38基因沉默同样也可抑制BMP9诱导的ALP活性、OPN表达、钙盐沉积以及裸鼠皮下异位成骨.因此,BMP9可通过活化p38激酶途径调控间充质干细胞C3H10T1/2成骨分化.

    • >Perspectives
    • 中国干细胞研究一瞥

      2011, 38(11):1011-1014.

      摘要 (1989) HTML (7) PDF 0.00 Byte (3516) 评论 (0) 收藏

      摘要:2010 has seen rapid progress in stem cell research in China. Not only the major funding agencies had provided extensive funding to stem cell research, the publications by Chinese stem cell biologists also flourished in top-notch scientific journals. In this special review, we highlighted some recent studies that had been published in Science China Life Sciences and Cell Research, two key SCI journals based in China. Not surprisingly, these studies mainly focused on some of the highly pursued stem cell types: embryonic stem cells (ES cells), induced pluripotent stem cells (iPSCs), neural stem cells (NSCs) and mesenchymal stem cells (MSCs).
      1 Research on embryonic stem cells
      ES cells are derived from the inner cell mass of blastocysts and are capable of infinite self-renewal and differentiation into various cell lineages within the three germ layers. A fundamental question in stem cell biology is what are the molecular mechanisms underlying lineage specifications along the developmental process. To study the transition of cell fate from A to B, it is important to use a system that can monitor the cell identity in an accurate and timely manner. Ho et al. found that, compared with protein markers and gene expression profiling, a change in the cell signaling network more sensitively reflects cell fate transition during the early differentiation of mouse ES cells[1]. In this study, the authors compared the mouse ES cells with the 2-day embryoid bodies (EBs) in terms of expression of stem cell markers (Oct4, Sox2 and Nanog etc.) as well as the cell signaling networks in response to extracellular stimuli, leukemia inhibitory factor (LIF) and fibroblast growth factor 8 (FGF8). mRNA levels of Oct4, Sox2 and Nanog and protein levels of Oct4 were not significantly different between mouse ES cells and up to 4-day EBs. Using phospho-specific antibody arrays and Western blot, the authors examined the activity of 8 signaling nodes (Erk1/2, p38, Akt1/2, Gsk3α/β, Stat3, β-catenin, Smad1, and Smad2) that play critical roles in mouse ES cell functionality, and found a clear difference in the signaling network status between ES cells and 2-day EBs when probed with LIF or FGF8 stimulation. The authors proposed that the cell signaling network may represent a fundamental characteristic of a cell and can more precisely reveal the cell identity and predict the cell behavior under certain perturbations. However, a drawback of this system is that it is based on the examination of a population of heterogeneous cells and cannot monitor cell fate at a single cell level, which could be very instrumental in studying the very early embryo development. In addition, live cell staining with specific markers may also be preferred when real time dynamics of a cell needs to be studied.
      One important component of the signaling network in a stem cell is TGF-β family signaling, which plays crucial roles in the regulation of ES cell self-renewal and differentiation[2]. In an article published by Fei and Chen, the authors summarized the roles of TGF-β family (TGF-β, bone morphogenetic protein (BMP), Activin and Nodal) in different aspects of an ES cell behavior that includes self-renewal and pluripotency maintenance, as well as ES cell differentiation into the ectodermal, mesodermal, endodermal and trophectodermal lineages. Particularly, Chen et al. found that Smad2-mediated Activin/Nodal signaling is dispensable for the self-renewal of mouse ES cells, but is critical for the mesendodermal differentiation, with Tapbp as a key downstream player[3].
      In another study published by Bai et al.[4], the authors attempted different approaches to promote cardiomyocyte differentiation from human ES cells, and found that treatment with 0.1 mmol/L ascorbic acid alone, or more notably in combination with 10 μmol/L 5-aza-2-deoxycytidine, can dramatically increase the number of beating clusters within EBs —— a readout for cardiomyocyte specification.
      A study reported by Li's lab[5] demonstrated an interesting correlation between the metabolic properties and the states of chicken embryonic stem cells. Li et al. found that undifferentiated chicken ES cells maintain a high glycogen level by directing glucose flux towards the glycogenic pathway. However, upon the commencement of differentiation programs, the metabolism is switched from a glycogenic to a glycolytic pathway, suggesting that the cellular level of glycogen may indicate a chicken ES cell state. In addition, supply with glucose-6-phosphate can enhance the survival of chicken ES cells in vitro.
      2 Research on induced pluripotent stem cells
      iPSCs are pluripotent cells derived from a non-pluripotent cell, normally a somatic cell, by forced expression of defined factors. iPSCs are similar to natural ES cells in many aspects and meanwhile retain almost identical genetic information of donor cells and can also avoid the controversial use of embryos[6-7]. Through tetraploid complementation assay, Zhou et al. showed that iPSCs can produce viable mice, which confirms the true pluripotency of iPSCs and opens a new avenue for animal cloning[8]. However, only a very small fraction of mouse iPSCs can pass the tetraploid complementation test and give rise to live offspring. To increase the efficiency of animal cloning, Zhou et al. combined the two approaches, iPSC and nuclear transfer (NT) techniques[9]. While no mouse embryonic fibroblast (MEF)-NT (nuclei of MEF transferred to enucleated metaphase Ⅱ oocytes) embryos developed into live animals, about 1% of iPSC-NT embryos gave rise to live mice. This combined approach may provide a new route to obtaining cloned animals from resistant donor species and facilitate the generation of transgenic animal models.
      A drawback of the iPSC technique when it was first reported by Yamanaka et al. was the low efficiency[10]. To induce mouse iPS cells, MEFs can be used as the start cells and be infected with virus encoding the "Yamanaka factors", Oct4, Sox2, Klf4 and c-Myc. After that, the infected MEFs are cultured on feeder cells in the induction medium until the iPSC colonies emerge. Mouse ES cell growth medium containing 15% fetal bovine serum (FBS) is commonly used as the induction medium to facilitate the reprogramming process of MEFs. Zhou et al. found that replacement of FBS with 20% of knockout serum replacement (KOSR), a commercially available supplement, can significantly accelerate the reprogramming process, as well as augment the efficiency by more than 200 fold (~24% with KOSR versus ~0.1% with FBS at Day 20 post-infection)[11]. In addition, the iPS cells obtained by this method are of good quality and possess full developmental potentials including germ-line contribution in chimeric mice and full-term development of tetraploid complementation embryos.
      3 Research on neural stem cells
      In vertebrates, gastrulation creates an embryo with three germ layers. The interaction between the dorsal mesoderm and the overlying ectoderm directs the ectoderm to form the hollow neural tube, which will differentiate into the brain and spinal cord. Epigenetic regulation has been shown to play important roles in the development of the nervous system. In a recent report, Chen et al. discovered a new histone demethylase, KIAA1718 (KDM7A), which is specific for histone H3 lysine 9 and lysine 27 —— two epigenetic marks associated with transcription repression. Expression of KIAA1718 increases along with the neural differentiation of mouse ES cells and knockdown of KIAA1718 blocks such neural differentiation. Chen et al. also identified FGF4 as the direct target of KIAA1718 that mediates the pro-neural differentiation effect[12].
      NSCs have been successfully isolated from various regions of the embryonic central nervous system[13]. However, whether NSCs can be isolated from the embryonic peripheral nervous system has not been completely explored. Gu et al. attempted to answer this question by using fetal rat dorsal root ganglia[14]. The progenitor-like cells isolated from dorsal root ganglia resemble neural crest progenitors. Such cells formed neurospheres and generated secondary and tertiary spheres by cloning assays, and could also give rise to neurofilament-expressing neurons and S100-expressing Schwann cell-like cells.
      The fate of NSCs is largely based on the delicate balance between intrinsic and extrinsic factors. Extracellular matrix contains important components that regulate the different aspects of NSCs. An optimal biomaterial may capitalize on this information to produce scaffolds to support the survival and differentiation of NSCs for regenerative approaches. In a recent report, Li et al. examined three different biomaterials, chitosan membranes, collagen gels, and chitosan-collagen membranes, and compared the effects of those materials on the survival, proliferation and differentiation of rat NSCs. Among the three, chitosan-collagen membranes seemed to show the best effect in supporting the survival and neuronal production from rat NSCs[15].
      It has long been debatable whether functional neurons may be derived from bone marrow-derived mesenchymal stem cells (BMSCs). The key issue has always been whether the neuron-like cells derived from MSCs demonstrate the electrophysiological properties of nerve cells[16-17]. Ge et al. tried to specifically direct BMSCs isolated from rhesus monkeys towards cholinergic neurons[18]. The authors compared four different conditions for neuronal differentiation, basal medium (bFGF and forskolin), basal medium+sonic hedgehog (SHH), basal medium +retinoic acid (RA), and basal medium+SHH+RA, and demonstrated that SHH+RA inducing group showed neuronal resting membrane potential and expressed high levels of synapsin and acetylcholine. However, in this study, the membrane potential was only tested by using a fluorescent dye DiBAC4. The whole cell clamp technique could have been used to more directly and accurately measure the membrane potential and analyze other electrophysiological properties of the resulting cells.
      4 Research on mesenchymal stem cells
      MSCs are stem cells that can self-renew and differentiate into mesodermal lineages including chondrocytes, adipocytes, and osteocytes. Due to their low immunogenicity and easy access from tissues such as bone marrow and adipose tissue, MSCs hold great promise in prospective clinical applications[19-20]. In the study reported by Qiu et al.[21], an alternative source material, placenta, was used to obtain MSCs. Human placenta-derived stem cells (hPDSCs) resemble MSCs in terms of surface marker expression and the differentiation potentials. hPDSCs possess a high proliferative ability and can be induced into type Ⅱ collagen-expressing chondrocytes. When seeded into collagen sponges, followed by introduction into nude mice, hPDSCs could develop into cartilage tissues in vivo, suggesting a potential utility in repair of cartilage defects.
      It has been shown that bone marrow derived stem cells participate in the regeneration process after myocardium infarction, possibly by increasing growth factor production and/or decreasing proinflammatory cytokine production, rather than a direct replacement of the damaged cardiomyocytes[22-23]. Treatment with estrogen prior to MSC infusion leads to a better recovery from myocardium infarction, compared with non-treated MSC group. Estrogen treatment can significantly augment the production of vascular endothelial growth factor (VEGF) from MSCs. Hu et al. also found that estrogen treatment can markedly reduce the apoptosis and increase the viability and proliferation of MSCs[22], indicating that ex vivo treatment with estrogen may maximize the clinical potential of MSCs for repair of ischemic myocardium.
      MSCs also have great potentials for treating disorders of the immune system. Shi's lab looked into the underlying mechanisms of the immunosuppressive effects of MSCs and found that priming with pro-inflammatory cytokines is necessary for MSCs to exert immunosuppressive functions[24]. Upon stimulation, MSCs secrete chemokines to attract immune cells into the proximity to MSCs, and suppress the immune functions through both cell-cell contact and soluble factors, with nitric oxide or indoleamine 2, 3-dioxygenase being key mediators in mouse MSCs and human MSCs, respectively.

    • 东亚地区碳循环研究新进展

      2011, 38(11):1015-1019.

      摘要 (2818) HTML (87) PDF 0.00 Byte (3595) 评论 (0) 收藏

      摘要:近百年来,温室效应的日益加剧,引发了全球温暖化、海平面上升等一系列重大环境问题,碳循环研究因此而受到全球范围的普遍关注和重视.东亚地区因其独特的气候特征,多样化的物种和生态系统,以及活跃的人类活动而成为世界碳循环研究中不可或缺的一部分. 在中、日、韩三国联合启动东亚碳循环前沿研究计划(A3 Foresight Program)三周年之际,《中国科学 生命科学》(Science China Life Sciences) 2010年第7期发表了东亚地区碳循环研究专题,包括14篇述评和研究论文,从区域碳储量及其变化特征,不同地带森林生态系统的碳源汇变化,草地和农田生态系统的碳储量和碳循环研究中的新方法等多个方面系统展示了东亚地区碳循环研究的最新进展.

    • >研究报告
    • 嗅球僧帽细胞具有编码气味空间信息的能力

      2011, 38(11):1020-1026.

      摘要 (3767) HTML (105) PDF 0.00 Byte (4981) 评论 (0) 收藏

      摘要:刺激源的方位是刺激的重要特性之一.行为学的研究发现,动物能够利用气味到达左右鼻腔的时间差和强度差信息对气味方位进行感知,但作为嗅觉系统第一神经中枢的嗅球,是否具有利用两侧鼻间差信息对气味方位进行编码的能力一直受到质疑.为探讨该问题,在本研究中通过比较嗅球中84个僧帽细胞对同侧气味刺激、对侧气味刺激以及对侧气味刺激略先于同侧气味刺激时的反应,发现有29个僧帽细胞可被同侧气味所兴奋,其中18个虽然对对侧气味刺激不反应,但对侧气味的存在却能显著降低其对同侧气味刺激的反应.另外,50个僧帽细胞在只给予同侧或对侧气味刺激时不反应,但其中11个在对侧刺激略先于同侧刺激的方式给出气味时,表现出明显的兴奋性反应.我们的研究结果一方面提示僧帽细胞具有编码气味到达两个鼻腔的时间差,或气味源位置信息的能力;另一方面也表明对侧刺激不仅能对同侧嗅球僧帽细胞产生抑制效应,还可能存在目前还不明确的机制而产生兴奋效应.

    • 海马参与工作记忆目标匹配增强及其时间过程——基于颅内脑电的研究

      2011, 38(11):1027-1035.

      摘要 (5326) HTML (247) PDF 0.00 Byte (5482) 评论 (0) 收藏

      摘要:已有的研究结果表明,海马参与记忆的编码和提取,并且它会受到新发生事件与已存储记忆匹配或者不匹配的影响.先前的功能磁共振研究报道,在延迟匹配任务中,目标匹配增强作为一种工作记忆成分,与物体性质和位置的整合有关,能够显著地激活海马体部.但是,关于这一过程的时间信息目前尚不清楚.本研究利用特定癫痫病人在双侧海马植入的深部电极, 跨被试间电极触点位置基本一致,因此具有较高的空间分辨率和时间分辨率的优势.我们发现,左侧海马体部在目标匹配增强中起着重要作用.同时,这种效应发生在探测刺激出现后600~650 ms,大约在知觉匹配增强或者P300等知觉效应后200 ms.另外,对于每一个被试,目标匹配增强的潜伏期与平均反应时成正相关.结果揭示,当工作记忆的任务与性质-位置捆绑有关时,海马参与并起重要作用.结果说明,目标匹配增强效应在知觉过程之后发生,表明了工作记忆不同成分在海马的分离.

    • 不同强度工频磁场对皮层神经元瞬时外向钾离子通道的影响

      2011, 38(11):1036-1042.

      摘要 (3876) HTML (27) PDF 0.00 Byte (4985) 评论 (0) 收藏

      摘要:人们对电磁辐射越来越关注,但是工频磁场产生的生物效应并不确定.选用1、5、10 mT的工频磁场照射急性分离的小鼠皮层神经元(15 min),应用全细胞膜片钳技术离线记录瞬时外向钾通道电流,研究工频磁场对离子通道的影响.结果显示:工频磁场抑制通道的电流密度,并且1 mT、5 mT及10 mT工频磁场的抑制率分别为(63.0 ± 2.2)%、(55.0 ± 1.7)%和(38.0 ± 1.8)%.工频磁场影响离子通道的激活和失活特性,半数激活电压和半数失活电压变小.不同强度工频磁场对离子通道产生的影响 程度不同,其中1 mT 工频磁场对通道电流的抑制率最大,5 mT工频磁场对通道的半数激活电压和半数失活电压影响最大,10 mT工频磁场增大了通道的失活斜率因子.研究结果表明,工频磁场影响了细胞膜上离子通道蛋白质构象的变化,进一步影响了离子通道的正常功能.

    • 亚健康便秘人群结肠黏膜蛋白质组的筛选鉴定与临床应用

      2011, 38(11):1043-1051.

      摘要 (3944) HTML (15) PDF 0.00 Byte (5110) 评论 (0) 收藏

      摘要:筛选亚健康便秘人群结肠黏膜变化的分子标志物,为亚健康便秘人群的结肠黏膜改变机制提供理论依据.采用双向凝胶电泳(two-dimensional electrophoresis,2-DE)对亚健康便秘人群及健康志愿者结肠黏膜组织进行蛋白质分离,ImageMaster 2D Elite分析软件进行图像分析,基质辅助激光解吸电离飞行时间质谱(matrix-assisted laser desorption/ionization time of flight mass spectrometry, MALDI -TOF-MS)得到相应的肽质量指纹图(peptide mass fingerprint, PMF),搜索数据库鉴定差异蛋白.建立了亚健康便秘人群及健康志愿者结肠黏膜组织2-DE图谱,分析出其凝胶的平均蛋白质点数(501.00 ± 37.16,536.00 ± 41.63),两者平均差异蛋白质点数为46.00±7.82,取20个表达量明显改变的蛋白质点进行质谱分析,鉴定出17个蛋白质.其中7个蛋白质点表达下调,10个蛋白质点表达上调.差异蛋白质点包括蛋白质合成与分解、分子伴侣、氧化还原调节及信号传导等相关蛋白质.随即应用免疫印迹(Western blot)技术分析差异蛋白β-actin、YWHAZ及PBP-Ⅰ(phosphatidylethanolamine- binding protein Ⅰ)在两类组织中的表达水平及临床意义.结果表明,亚健康便秘人群和健康志愿者的结肠黏膜组织蛋白表 达存在差异,β-actin、YWHAZ表达下调及PBP-Ⅰ上调参与了亚健康便秘的发生,对此状态进行合理干预,可使身体向健康转化.

    • 二苯乙烯苷对氧化诱导内皮细胞凋亡及Caspase-3和PARP表达的影响

      2011, 38(11):1052-1059.

      摘要 (4220) HTML (64) PDF 0.00 Byte (4991) 评论 (0) 收藏

      摘要:为研究二苯乙烯苷对过氧化氢(H2O2)诱导人脐静脉内皮细胞凋亡的影响并初步探讨二苯乙烯苷抗凋亡的可能机制,采用不同浓度H2O2和二苯乙烯苷处理内皮细胞24 h,以MTT法检测细胞生长活力、Hoechst33258染色观察细胞形态、流式细胞仪检测凋亡率等方法筛选造模内皮细胞凋亡的H2O2浓度和二苯乙烯苷最佳的抗内皮细胞凋亡作用浓度.RT-PCR、Western-blot分别检测Caspase-3、PARP mRNA及蛋白质的表达.结果发现,与空白对照组相比,300 μmol/L H2O2作用后,内皮细胞增殖明显受到抑制,Hoechst33258染色可见大量凋亡细胞,细胞凋亡率显著增加,流式细胞仪检测出明显的凋亡峰, Caspase-3和多聚腺苷酸二磷酸核糖基聚合酶(PARP)的表达量显著增加.经二苯乙烯苷处理后,随着二苯乙烯苷浓度增加,细胞的增殖率随之增加,凋亡细胞数减少,凋亡率逐渐降低,与H2O2组比较,10 μmol/L的二苯乙烯苷能够显著提高细胞增殖率,降低细胞凋亡率,并显著减少Caspase-3和PARP表达.以上结果表明,二苯乙烯苷能够抑制由H2O2诱导的人脐静脉内皮细胞凋亡,增加细胞生长活性,降低细胞凋亡率,其作用机制可能与下调Caspase-3和多聚腺苷酸二磷酸核糖基聚合酶(PARP)的表达有关.

    • 洛美沙星对Bloom综合征解旋酶生物学特性影响的机理研究

      2011, 38(11):1060-1071.

      摘要 (3687) HTML (133) PDF 0.00 Byte (5270) 评论 (0) 收藏

      摘要:Bloom 综合征解旋酶(BLM)是RecQ家族DNA解旋酶中的一个重要成员,参与了DNA复制、修复、转录、重组以及端粒的维持等细胞代谢过程,在维持染色体的稳定性中具有重要作用.BLM解旋酶的突变可导致Bloom综合征.Bloom综合征是一种罕见隐性常染色体遗传疾病,患者遗传不稳定,并易患多种类型癌症.洛美沙星(LMX)可以抑制细胞内多种酶,并通过结合DNA干扰DNA代谢,从而治疗多种疾病,但是其具体的作用机理还未完全清楚.运用荧光偏振技术和自由磷检测技术,研究了LMX对BLM642~1290解旋酶DNA结合活性、解链活性和ATP酶活性的影响.运用荧光及紫外吸收光谱法研究了LMX与解旋酶结合的结合常数、结合位点数、作用力类型、结合距离等参数.结果表明,LMX与解旋酶之间能自发进行反应,两种分子有一个结合位点,通过静电引力和疏水作用力形成稳定的BLM-LMX复合物,且解旋酶的内源荧光被LMX静态猝灭,主要原因是非辐射能量转移.在这一过程中,LMX能抑制解旋酶的解链活性和ATP酶活性,而促进解旋酶的DNA结合活性. LMX对BLM解旋酶生物学活性影响的机理可能是LMX使解旋酶通过别构机制影响其ATP酶活性,并使酶的构象维持在较低解链活性的状态,通过抑制ATP催化水解与解链过程的偶联和阻止解旋酶的易位,从而抑制其解链.LMX能够促进解旋酶的DNA结合活性,可能是因为其C-6和C-7上的取代功能基团可以增加酶活力,以及增强药物、酶和DNA的结合,从而形成药物-酶-DNA复合物.这些结果为研究以DNA解旋酶为药物靶标的分子机理和理解喹诺酮类药物的作用机理奠定相关理论基础.

    • 基于CT的股骨有限元模型的建立及髋关节中空多孔假体植入后受力分布的初步研究

      2011, 38(11):1072-1078.

      摘要 (3733) HTML (2) PDF 0.00 Byte (4520) 评论 (0) 收藏

      摘要:利用有限元分析的方法,对髋关节中空多孔假体植入后的受力分布改变进行研究,为改进中空多孔人工关节假体的设计提供依据.建立了股骨和假体三维有限元模型,应用有限元分析软件Ansys5.7模拟单腿负重状态,考察应力分布并进行比较.使用SPSS Statistics 17.0软件进行分析处理,绘制折线图.结果表明:a.开孔后张力侧最大压应力有所减小,开孔部位的应力水平变化不明显.b.与周围骨质形成连接后孔缘局部应力增加,张力侧受力改变不明显.c.短柄假体受力模式仍为远端应力集中;张力侧应力减小,开孔部位应力明显增加.d.下孔受力均大于上孔,受力方向基本一致.

最新一期

年第卷第

文章目录

过刊浏览

年份

刊期

浏览排行

引用排行

下载排行