SKF38393对DRG神经元GABA-激活电流的抑制

在大鼠新鲜分离DRG神经元标本上应用全细胞膜片作记录,观察了多巴胺D_1受体的选择性激动剂(±)SKF38393HCI对GABA-激活电流的作用。大部分受检细胞(60/70)对GABA敏感。10~(-6)～10~(-3)mol/L GABA可引起呈剂量依赖性的明显去敏感作用的内向电流。在60个对GABA敏感的细胞中,预加SKF38393引起的膜反应如下:(1)外向电流(7/60);(2)内向电流(5/60);(3)无反应(48/60)。与GABA激活的内向电流相比,SKF38393激活电流幅值较小,无明显去敏感现象。预加SKF38393 30秒对GABA-激活电流幅值的影响如下:产生抑制作用的为88.33％(53/60),增强的为1.66％(1/60),无明显作用的为10.0％(6/0)。SKF38393对10~(-4)mol/L的GABA-激活电流的抑制作用依赖于SKF38393的浓度,在其浓度为10~(-4)、10~(-5)、10~(-6)、10~(-7)mol/L时对GABA-激活电流的抑制(±)分别为46.5％±2.3(n=8)、35.5％±1.2(n=8)、26.8％±1.5(n=7)、24.8％±2.6(n=7)。通过应用二次膜片作(repatch)技术在同一细胞(n=2)以及不同细胞组间(n=14)进行对比,证明:细胞内加蛋白激酶抑制剂H-7后,SKF38393对GABA的抑制作用完全清除。结果提示:SKF38393对GABA-激活电流的抑制作用可能是由于SKF38393激活D_1受体后通过胞内转导机制,使GABA受体通道复合体胞内磷酸化所致。     

Baclofen对大鼠新鲜分离DRG神经元GABA和NMDA激活电流的抑制作用

用全细胞膜片箝技术在大鼠新鲜分离的背根神经节 (DRG)细胞上观察到baclofen对GABA和NMDA激活电流有调制作用。单独给予DRG细胞baclofen (1～ 10 0 μmol/L)未记录到可测的电流改变 ,但预加baclofen对GABA和NMDA激活电流具有明显的抑制作用 ,且呈剂量依赖性。 10 0 μmol/Lbaclofen对GABA和NMDA激活电流分别抑制(5 1.2± 10 .9) % (X±SE ,n=8,P <0 .0 1)和 (6 4 .1± 2 1.1) % (X±SE ,n=6 ,P <0 .0 1) ,此抑制作用是可逆的 ,可被GABAB 受体拮抗剂saclofen(10 0 μmol/L ) 所取消 (n =4 )。     

D_2受体激动剂R(一)—NPA对DRG神经元GABA-激活电流的抑制作用

应用全细胞膜片钳记录技术在大鼠新鲜分离DRG神经元上,观察预加多巴胺D_2受体选择性激动剂R(—)—NPA对GABA—激活电流的调制作用.绝大部分受检细胞86.2%(50/58)对外加GABA敏感.10~(-6)～10~(-3)mol/LGABA 引起一剂量依赖性有明显去敏感作用的内向电流.对GABA敏感的50个受检细胞中13个细胞引起一较大的无明显去敏感的内向电流,其他的无反应.预加R(一)—NPA30秒后再加GABA,则对GABA—激活电流幅值的影响如下:抑制的为76%(38/5O),增强的为2%(1/50),无明显作用的为22%(11/5O).在其浓度为10~(-4)mol/L、10~(-5)mol/L、10~(-6)mol/L、10~(-7)moV/L时抑制(X±SE)分别为19.1%12.8(n=6)、42.49%±3.2(n=6)、83.6%±1.2(n=6)、8.69%±1.8(n=6).细胞内加蛋白激酶抑制剂H7后,R(—)—NPA对GABA的抑制作用完全消除(n=16).     

组织胺对大鼠DRG神经元ATP-激活电流的抑制作用

目的:探讨组织胺对大鼠DRG神经元ATP-激活电流的调制作用.方法:采用全细胞膜片钳技术,在新鲜分离的大鼠背根神经节细胞上进行.结果:实验观察到组织胺在DRG神经元可引起内向电流,并有明显的浓度依赖性.在被检测的DRG神经元中,85%(30/35)的细胞对ATP敏感,可引起一浓度依赖性的去敏感的内向电流.预加10-8、10-7、10-6、10-5、10-4mol/L组织胺后,对ATP-激活电流的抑制分别是:(12.50±3.2%(n=5)、(24.49±3.5%(n=5)、(35.18±4.5%(n=6)、(32.62±5.8%(n=8)、(23.53±4.2%(n=5),呈浓度依赖性.结论:组织胺对大鼠DRG神经元ATP-激活电流有明显的抑制作用.     

尼氟灭酸对CCI模型鼠DRG神经元GABA介导膜电流的影响

为观察尼氟灭酸(NFA)对坐骨神经慢性压迫损伤(CCI)所导致的神经病理性痛大鼠的背根神经节(dorsal root ganglion,DRG)神经元上GABAA受体激活电流的影响,探讨尼氟灭酸在神经病理性疼痛时在脊髓水平的作用及可能机制。采用如下方法:(1)制作CCI模型。(2)运用热板实验检测CCI组、假手术组术侧下肢热缩足反射潜伏期的变化。(3)运用全细胞膜片钳技术记录CCI模型组术侧、假手术组术侧、正常组DRG神经元上GABAA受体激活电流的幅度。(4)记录尼氟灭酸对正常组和CCI组术侧DRG神经元上GABAA受体激活电流的调节作用。结果显示,(1)CCI组术侧下肢热缩足反射潜伏期明显缩短。(2)GABA(1~1000μmol/L)可以使DRG神经元产生浓度依赖的内向电流(P0.05,n=10)。(3)CCI组1~100μmol/L GABA激活电流幅值显著小于假手术组和正常对照组(P0.01,n=6)。假手术组和正常对照组GABA电流差异无统计学意义。(4)NFA(1~100μmol/L)对正常组、CCI组的DRG神经元上GABA激活的电流均有抑制作用,该抑制作用具有浓度依赖性,且正常组的抑制作用更明显(P0.01,n=5)。由此可知,NFA对CCI模型大鼠DRG神经元GABA激活电流的抑制作用相比较正常组有所减弱,这可能是由于CCI模型的DRG神经元上钙激活氯通道的数量增加。     

可乐定对DRG神经元膜GABA激活电流的抑制作用

在新鲜分离大鼠DRG细胞上应用全细胞膜片钳记录证明:(1)绝大多数DRG细胞对GABA(10~(-5)～10~(-3)mol/L)敏感(72/75),产生有明显去敏感的、浓度依赖性的内向流;(2)大多数受检细胞对可乐定(10~(-8)～10~(-4)mol/L)无反应(60/72),仅少数细胞引起很小的内向流(12/72);(3)预加可定30～120sec后,GABA-激活电流受到明显抑制(51/72),此作用可被育亨宾(10~(-4)～10~(-5)mol/L)所阻断。如可乐定浓度为10~(-5)mol/L时,抑制为44.35％;(4)预加10~(-5)mol/L的可乐定使GABA激活电流的量效曲线明显右移,而Kd值相近,最大浓度时的GABA激活电流抑制30.5％;(5)预加β-受体激动剂异丙肾上腺素(10~(-4)～10~(-5)mol/L)对GABA激活电流无影响(n=9);(6)胞内预加H-7(10~(-4)mol/L),20个细胞中除1例以外,可乐定的抑制作用均明显地被阻断。本文结果提示:可乐定对GABA激活电流的抑制可能是由于α_2-受体激活后。通过胞内转导,而引起GABAa受体蛋白磷酸化的结果。     

大黄素对辣椒素诱导的TRPV1通道电流的抑制作用

本研究通过显微注射技术将TRPV1 cRNA(1ng/nL)注射至非洲爪蟾卵母细胞(20nL/个)体内,放置于G-ORi培养液中,并在(19±1)℃的恒温培养箱内表达.同时利用灌流技术将不同浓度梯度的大黄素、辣椒素按照设计顺序依次灌流进入流动腔,同时控制流速保证非洲爪蟾卵母细胞完全浸没于流动腔内.使用双电极电压钳技术记录0.1,1.0,10.0,50.0μmol/L浓度梯度的大黄素对500nmol/L浓度的辣椒素激活TRPV1电流的影响.得到大黄素作用辣椒素激活TRPV1通道的抑制作用表现出浓度依耐性和电压非依赖性,IC50=38μmol/L,Hill系数n=0.5.结果表明了大黄素对TRPV1位点的相互作用是负协同的,在天然药物里面是一类比较弱的拮抗剂,且大黄素在ORi溶液中开始析出沉淀的浓度在50~60μmol/L之间.我们首次发现了大黄素能够抑制TRPV1通道电流,这可能为开发新的镇痛药物提供理论基础.     

GABA促进小鼠离体胃胃酸分泌活动的机制探讨

为了探讨γ-氨基丁酸(GABA)对小鼠离体胃胃酸分泌(GAS)的调节作用和机制,在体外37℃缓冲溶液中培育小鼠全胃标本,测定灌流液的pH值。结果表明:丙谷胺(2、6×10-7mol/L),可显著地抑制胃酸分泌。GABA(2～10×10-7mol/L)则以一种浓度依赖的方式显著地促进胃酸分泌,若用丙谷胺(6×10-7mol/L)和不同浓度的GABA共同灌流胃,则显著阻断GABA的促进效应,逻辑斯谛曲线(Logisticcurve)显示这种阻断是不完全的。西咪替丁(Cim,10×10-7mol/L)明显抑制胃酸分泌,并不完全阻断GABA对胃酸分泌的促进效应。若用丙谷胺(6×10-7mol/L)和西米替丁(Cim,10×10-7mol/L)与GABA(4～10×10-7mol/L)共同灌流胃,对GABA促进胃酸分泌的效应仍显示不完全阻断作用。结果提示:GABA可能通过G细胞或/和ECL细胞间接促进壁细胞泌酸;GABA也可能直接激活壁细胞,促进胃酸分泌。     

大鼠背根神经节神经元的分离方法及电生理特征探讨

在获取大鼠背根神经节神经元后,全细胞膜片钳技术记录动作电位和钠电流,探讨大鼠背根神经节细胞的分离方法和细胞形态以及电生理特征.结果显示,本实验能得到完整圆形或椭圆长条形的大鼠背根神经节体.正常的单个背根神经节神经元呈圆形或椭圆形,大小不等,胞膜清晰,折光性好,隐约可见细胞核.在背根神经节细胞上记录的动作电位呈正立锐角三角形,静息电位小,动作电位时程短.背根神经节神经元的钠通道最大电流密度为(-62.04±4.45)pA/pF,几乎能被河豚毒素(TTX)完全抑制.本实验分离方法简单易行,背根神经节神经元容易获得和辨认,电生理特征明确,适用于神经系统疾病的电生理特征研究和治疗药物观察.     

GABA引起正常和病理性疼痛大鼠DRG神经元去极化反应的比较

为探究GABA在痛觉信息传递中的作用,观察分析了γ-氨基丁酸(GABA)在神经病理性疼痛中的作用。制备神经病理性疼痛大鼠模型,取其L4-L5背根神经节(dorsal root ganglion,DRG),运用细胞内微电极记录技术观察在灌流GABA及其受体阻断剂的情况下,引起DRG神经元膜电位的变化。结果表明,病理性疼痛模型组大鼠的DRG神经元对不同浓度GABA引起的去极化反应均明显小于正常对照组大鼠(P0.05),这说明神经病理性疼痛可通过减弱GABA介导的突触前抑制易化痛觉信息的传递。     

Markedness and its Interpretation in Language Use

Language markedness is a common phenomenon in languages, and is reflected from hearing, vision and sense, i.e. the variation in the three aspects such as phonology, morphology and semantics. This paper focuses on the interpretation of markedness in language use following the three perspectives, i.e. pragmatic interpretation, psychological interpretation and cognitive interpretation, with an aim to define the function of markedness.     

Characterization of Ordovician carbonate reservoirs, southeastern Saskatchewan, Canada

The discovery of the prolific Ordovician Red River reservoirs in 1995 in southeastern Saskatchewan was the catalyst for extensive exploration activity which resulted in the discovery of more than 15 new Red River pools. The best yields of Red River production to date have been from dolomite reservoirs. Understanding the processes of dolomitization is, therefore, crucial for the prediction of the connectivity, spatial distribution and heterogeneity of dolomite reservoirs.The Red River reservoirs in the Midale area consist of 3～4 thin dolomitized zones, with a total thickness of about 20 m, which occur at the top of the Yeoman Formation. Two types of replacement dolomite were recognized in the Red River reservoir: dolomitized burrow infills and dolomitized host matrix. The spatial distribution of dolomite suggests that burrowing organisms played an important role in facilitating the fluid flow in the backfilled sediments. This resulted in penecontemporaneous dolomitization of burrow infills by normal seawater. The dolomite in the host matrix is interpreted as having occurred at shallow burial by evaporitic seawater during precipitation of Lake Almar anhydrite that immediately overlies the Yeoman Formation. However, the low δ18O values of dolomited burrow infills (-5.9‰～ -7.8‰, PDB) and matrix dolomites (-6.6‰～ -8.1‰, avg. -7.4‰ PDB) compared to the estimated values for the late Ordovician marine dolomite could be attributed to modification and alteration of dolomite at higher temperatures during deeper burial, which could also be responsible for its 87Sr/86Sr ratios (0.7084～0.7088) that are higher than suggested for the late Ordovician seawaters (0.7078～0.7080). The trace amounts of saddle dolomite cement in the Red River carbonates are probably related to "cannibalization" of earlier replacement dolomite during the chemical compaction.     

低渗透非均质砂岩油藏启动压力梯度研究

理论推导与室内实验相结合,建立了低渗透非均质砂岩油藏启动压力梯度确定方法。首先借助油藏流场与电场相似的原理,推导了非均质砂岩油藏启动压力梯度计算公式。其次基于稳定流实验方法,建立了非均质砂岩油藏启动压力梯度测试方法。结果表明:低渗透非均质砂岩油藏的启动压力梯度确定遵循两个等效原则。平面非均质油藏的启动压力梯度等于各级渗透率段的启动压力梯度关于长度的加权平均;纵向非均质油藏的启动压力梯度等于各渗透率层的启动压力梯度关于渗透率与渗流面积乘积的加权平均。研究成果可用于有效指导低渗透非均质砂岩油藏的合理井距确定,促进该类油藏的高效开发。     

On Tragic Consciousness In The Works By Ernest Hemingway

As an American modern novelist who were famous in the literary world, Hemingway was not a person who always followed the trend but a sharp observer. At the same time, he was a tragedy maestro, he paid great attention on existence, fate and end-result. The dramatis personae's tragedy of his works was an extreme limit by all means tragedy on the meaning of fearless challenge that failed. The beauty of tragedy was not produced on the destruction of life, but now this kind of value was in the impact activity. They performed for the reader about the tragedy on challenging for the limit and the death.     

A computer generator for randomly layered structures

AcomputergeneratorforrandomlylayeredstructuresYUJia shun1,2,HEZhen hua2(1.TheInstituteofGeologicalandNuclearSciences,NewZealand;2.StateKeyLaboratoryofOilandGasReservoirGeologyandExploitation,ChengduUniversityofTechnology,China)Abstract:Analgorithmisintrod…     

An Index mechanism for multi-scale view in spatial databases

There are numerous geometric objects stored in the spatial databases. An importance function in a spatial database is that users can browse the geometric objects as a map efficiently. Thus the spatial database should display the geometric objects users concern about swiftly onto the display window. This process includes two operations:retrieve data from database and then draw them onto screen. Accordingly, to improve the efficiency, we should try to reduce time of both retrieving object and displaying them. The former can be achieved with the aid of spatial index such as R-tree, the latter require to simplify the objects. Simplification means that objects are shown with sufficient but not with unnecessary detail which depend on the scale of browse. So the major problem is how to retrieve data at different detail level efficiently. This paper introduces the implementation of a multi-scale index in the spatial database SISP (Spatial Information Shared Platform) which is generalized from R-tree. The difference between the generalization and the R-tree lies on two facets: One is that every node and geometric object in the generalization is assigned with a importance value which denote the importance of them, and every vertex in the objects are assigned with a importance value,too. The importance value can be use to decide which data should be retrieve from disk in a query. The other difference is that geometric objects in the generalization are divided into one or more sub-blocks, and vertexes are total ordered by their importance value. With the help of the generalized R-tree, one can easily retrieve data at different detail levels.Some experiments are performed on real-life data to evaluate the performance of solutions that separately use normal spatial index and multi-scale spatial index. The results show that the solution using multi-scale index in SISP is satisfying.     

Achieving Unusual States of Matter Under High Pressure

正The periodicity of the elements and the non-reactivity of the inner-shell electrons are two related principles of chemistry,rooted in the atomic shell structure.Within compounds,Group I elements,for example,invariably assume the+1 oxidation state,and their chemical properties differ completely from those of the p-block elements.These general rules govern our understanding of chemical structures and reactions.Using first principles calcula-     

Exchange-Correlation and Electronic Excitation Energies from Pairing Matrix Fluctuations

We have developed an adiabatic connection to formulate the ground-state exchange-correlation energy in terms of pairing matrix linear fluctuations.This formulation of the exchange-correlation energy opens a new channel for density functional approximations based on the many-body perturbation theory.We illustrate the potential of such approaches with an approximation based on the particle-particle Random Phase Approximation(pp-RPA).This re-     

Density Functional Theory for the Response of Periodic Systems to Electric Fields Based on the Vector Potential Approach

正The electronic and nuclear(structural/vibrational)response of 1D-3D nanoscale systems to electric fields gives rise to a host of optical,mechanical,spectral,etc.properties that are of high theoretical and applied interest.Due to the computational difficulty of treating such large systems it is convenient to model them as infinite and periodic(at least,in first approximation).The fundamental theoretical/computational problem in doing so is that     

On the Thermodynamic Limit for Responses to Static Electromagnetic Fields

For molecular systems,the quantum-mechanical treatment of their responses to static electromagnetic fields usually employs a scalar-potential treatment of the electric field and a vector-potential treatment of the magnetic field.Although the potential for each field separately is associated with the choice of an(unphysical)origin,the precise choice of the origin for the electrostatic field has little consequences for the results.This is different for the