Bis(7)-tacrine/tacrine对大鼠DRG神经元延时整流钾通道电流的调制作用

目的研究乙酰胆碱酯酶抑制剂bis(7)-tacrine/tac-rine[bis(7)-tetrahydroaminacrine]对大鼠DRG神经元的延时整流钾通道电流的调制作用。方法在急性分离的DRG神经元标本上,采用全细胞膜片钳技术记录钾通道电流,研究bis(7)-tacrine/tacrine对DRG神经元延时整流钾通道电流的影响和作用。结果 bis(7)-tacrine对延迟整流钾通道电流IDR具有浓度依赖性的抑制作用,其半量效浓度为(IC50)(0.72±0.05)μmol.L-1,而tacrine抑制的半量效浓度(IC50)(58.3±3.7)μmol.L-1。结论两种药物对DRG延时整流钾通道电流有浓度依赖性的抑制作用,bis(7)-tacrine的抑制强度高一个数量级,有利于抑制神经元的钾通道过于激活和兴奋,预防胞内钾离子过度丢失而引起的神经元凋亡,起到神经保护的作用。

Bis(7)-tacrine protects retinal ganglion cells against excitotoxicity via NMDA receptor inhibition

AIM: To investigate whether bis (7)-tacrine, a multifunctional drug, inhibits N-methyl-D-aspartate (NMDA) -activated current in retinal ganglion cells (RGC) and provides neuroprotection against retinal cell damage. METHODS: Purified RGC cultures were obtained from retinas of 1-3 days old Sprague-Dawley (SD) rats, following a two-step immunopanning procedure. After 7 days of cultivation, the inhibition of NMDA-activated current by bis(7) -tacrine was measured by using patch-clamp recording techniques. In animal experiments, RGCs were damaged after intravitreal injection of NMDA (5 mu L, 40nmol) in adult rats. Bis (7)-tacrine(0.05, 0.1, 0.2mg/kg) or memantine(20mg/kg) was intraperitoneal administered to the rats fifteen minutes before intravitreally injection of NMDA. RGC damage was analyzed by histologic techniques, TUNEL and retrograde labeling techniques. RESULTS: Whole-cell patch-clamp recordings demonstrated that NMDA (30 mu mol/L) resulted in approximately -50 pA inward currents that were blocked by bis (7)-tacrine (1 mu mol/L). Histological examination and retrograde labeling analysis revealed that bis (7)-tacrine induced a significant neuroprotective effect against NMDA-induced cell damage 7 days after NMDA injection. TUNEL staining showed that pretreatment with bis(7)-tacrine was effective in ameliorating NMDA-induced apoptotic cell loss in the retinal ganglion cell layer 18 hours after injection. CONCLUSION: Bis (7)-tacrine possesses remarkable neuroprotective activities against retinal excitotoxicity through inhibition of NMDA receptors.

Bis(7)-Tacrine, a Promising Anti-Alzheimer's Agent,Attenuates Glutamate-Induced Cell Injury in Primary Cultured Cerebrocortical Neurons of Rats

The effects of bis(7) tacrine, a novel dimeric acetylcholinesterase (AChE) inhibitor, on glutamate induced cell injury were investigated in primary cerebral cortical neurons of rats. Exposure of cultured neurons (12 days after plating) to 0.5 mmol/L glutamate for 30 min resulted in significant cell damage. Pretreatment with bis(7) tacrine (0.03 1.0 μmol/L) reduced the glutamate induced neurotoxicity in a concentration dependent manner and the maximal response was seen at 1 μmol/L with approximately 30% protection. A receptor binding assay showed that bis(7) tacrine can completely displace MK 801 binding to rat cortical membrane with an IC 50 of 0.57 μmol/L. These findings suggest that bis(7) tacrine can directly interact with N methyl D aspartate receptor channel complex, which may contribute to the inhibitor's protective effects against glutamate induced excitotoxicity. Thus, it is possible that anti glutamate/anti AChE synergism is responsible for potentially better Alzheimer's therapy of bis(7) tacrine relative to tacrine.

Inhibition of N-methyl-D-aspartate-activated Current by Bis(7)-tacrine in HEK-293 Cells Expressing NR1/NR2A or NR1/NR2B Receptors

In normal rat forebrain, the NR1/NR2A and NR1/NR2B dimmers are the main constitutional forms of NMDA receptors. The present study was carried out to determine the functional properties of the heteromeric NMDA receptor subunits and their inhibition by bis(7)-tacrine (B7T). Rat NR1, NR2A and NR2B cDNAs were transfected into human embryonic kidney 293 cells (HEK-293).The inhibition of NMDA-activated currents by B7T was detected in HEK-293 cell expressing NR1/NR2A or NR1/NR2B receptors by using whole-cell patch-clamp techniques. The results showed that in HEK-293 cells expressing NR1/NR2A receptor, 1μmol/L B7T inhibited 30μmol/L NMDA- and 1000μmol/L NMDA-activated steady-state currents by 46% and 40%, respectively (P>0.05; n=5), suggesting that the inhibition of B7T on NR1/NR2A receptor doesn’t depend on NMDA concentration, which is consistent with a non-competitive mechanism of inhibition. But for the NR1/NR2B receptor, 1μmol/L B7T inhibited 30μmol/L NMDA- and 1000 μmol/L NMDA-activated steady-state currents by 61% and 13%, re-spectively (P<0.05; n=6), showing that B7T appears to be competitive with NMDA. In addition, simultaneous application of 1μmol/L B7T and 1000μmol/L NMDA produced a moderate inhibition of peak NMDA-activated current, followed by a gradual decline of the current to a steady state. However, the gradual onset of inhibition produced by B7T applied simultaneously with NMDA was eliminated when B7T was given 5s before NMDA. These results suggested that B7T inhibition of NMDA current mediated by NR1/NR2B receptor was slow onset, and it did not depend on the presence of the agonist. With holding potentials ranging from -50 to +50 mV, the B7T inhibition rate of NMDA currents didn’t change significantly, and neither did the reversal potential. We are led to conclude that the NR1/NR2B recombinant receptor can serve as a very useful model for studying the molecular mechanism of NMDA receptor inhibition by B7T.

Bis(7)-Tacrine Ameliorates Cognitive Impairment Caused by Cerebral Hypoperfusion in Rats

The effects ofbis(7)-tacrine, a novel acetylcholinesterase inhibitor, on cognitive impairment and neuronal degeneration induced by permanent ligation of bilateral common carotid arteries (2VO) were investigated using the Morris water maze in rats. Once daily oral administration ofbis(7)-tacrine (0.025, 0.05 and 0.1 mg?kg?1) was started 14 days after 2VO operation. Over a three-week treatmentbis(7)-tacrine effectively reversed 2VO-induced spatial memory deficits in a dose-dependent fashion. Furthermore, histological observation showedbis(7)-tacrine decreased the neuropathological changes in the 2VO rats brain. These results suggest thatbis(7)-tacrine has therapeutic potential for the treatment of dementia caused by chronic cerebral hypoperfusion.

A SENSITIZED PHOTOINITIATION SYSTEM ——BIS (7-DIETHYLAMINO COUMARIN ) KETONE-3 AND DIPHENYLIODONIUM SALT COMBINATION

Bis (7- diethylaminocoumarin) ketone- 3(DACK) and diphenyliodonium salt (DPIO)combination as an effective photoinitiation system for radical polymerization has been investigated. The sensitized photolysis of DACK/DPIO leads to bleaching of DACK and decomposition of DPIO to generate initiating radical species. The electron transfer sensitization occurs mainly from the triplet state of DACK. The photobleaching obeyed a second-order kinetics and the rate constant was evaluated to be 31.3mol^(-1)·1·s^(-1) Photopolymerization of MMA initiated by DACK/DPIO was carried out in acetonitrile solution. The polymerization rate was found to be proportional to the concentration of DACK, DPIO and MMA with the exponents of 0.34, 0.40 and 1.0 respectively. The initiated efficiency is comparable to those of small molecular ketones.The sensitized photoinitiation mechanism has been discussed.

Bi_2Sn_2O_7粉体微波水热法制备及其吸附-可见光催化性能研究

以物质的量比为1∶1的Bi(NO3)3.5H2O和Na2SnO3.3H2O为原料,采用微波水热法合成Bi2Sn2O7粉体。采用XRD、SEM对粉体的晶相和形貌进行了表征,并以甲基橙为目标污染物,测试粉体的光催化性能。研究了合成时间、合成温度等因素对样品催化性能的影响,同时以KI、NBT及乙腈作为抑制剂,检测光催化过程产生的活性物质。结果表明:200℃、30 min微波水热合成的2 g/L Bi2Sn2O7粉体在暗光条件下搅拌2 h,对20 mg/L甲基橙溶液的吸附率为40%,将其置于250 W的卤素灯下光照2 h,甲基橙溶液的脱色率达95%以上。活性物种的检测表明光催化过程产生的主要活性物种为·OH和·O2-。

Bi^(3＋)掺杂对Sr2MgSi2O7：Eu^(2＋)荧光粉的结构及发光性能的影响(英文)

采用溶胶-凝胶法在还原气氛下制备了Sr2MgSi2O7∶Eu2+,xBi3+(x=0,0.02,0.04,0.06,0.08,0.1)荧光粉,并用XRD、TG-DTA及激发与发射谱仪对样品的结构及发光性能进行了表征。结果发现:单掺杂Bi3+的Sr2MgSi2O7样品的发射光谱所用的材料的激发光谱为一主峰为286 nm的宽带谱,这是由于激发态时Bi3+的3P1→1S0电子能级跃迁而造成的;单掺杂Eu2+的Sr2MgSi2O7样品的发射光谱所用的材料的激发光谱为一主峰为358 nm的宽带谱,这是典型的Eu2+的4f65d1→4f7跃迁而引起的。当Bi3+离子掺杂到Sr2MgSi2O7∶Eu2+样品的摩尔分数为0.04时,样品的发射强度是未掺杂Bi3+离子样品的1.9倍。

新型tacrine双联体对培养大鼠海马神经元NMDA受体作用位点的研究

目的:研究新型tacrine双联体bis(7)-tacrine对NMDA受体的作用位点.方法:大鼠海马神经元原代培养,全细胞膜片钳记录培养大鼠海马神经元上NMDA激活电流变化.结果:细胞外液pH值从8.1改变到6.7,在细胞外液中加入二硫苏糖醇(2 mmol/L)、精胺(10 mol/L)、镁离子(50～500 mol/L)或锌离子(5～20 mol/L)均不引起bis(7)-tacrine对NMDA电流抑制率的改变.电极内液中加入5 mol/L bis(7)-tacrine也未观察到外加的0.5 mol/L bis(7)-tacrine对30 mol/L NMDA激活电流抑制率的改变.0.5 mol/L bis(7)-tacrine及1 mol/L dizocilpine(MK-801)分别对30 mol/L NMDA激活电流抑制了36%和22%,而在两种药物都存在的条件下,30 mol/L NMDA电流仅被抑制了37%.结论:bis(7)-tacrine虽然不大可能作用于MK-801位点,但MK-801和bis(7)-tacrine之间可能存在着相互的负性调节作用.

Atenuation of scopolamine-induced deficits in navigational memory performance in rats by bis(7)-tacrine,a novel dimeric AChE inhibitor

目的：研究他克林的双体衍生物双（７）他克林对东莨菪碱引起的大鼠记忆障碍的影响．方法：采用大鼠Ｍｏｒｉｓ水迷宫固定平台的程序研究空间记忆．以他克林为对照药．结果：东莨菪碱（０３ｍｇ·ｋｇ－１，ｉｐ）使大鼠到达平台的潜伏期明显长于生理盐水对照组．双（７）他克林（０３５μｍｏｌ·ｋｇ－１，ｉｇ或ｉｐ）和他克林（８５２μｍｏｌ·ｋｇ－１ｉｇ；４２６μｍｏｌ·ｋｇ－１ｉｐ）均可对抗东莨菪碱导致的空间记忆障碍；在灌胃及腹腔注射途径下，双（７）他克林的效价，分别强于他克林２４及１２倍．结论：双（７）他克林明显改善东莨菪碱导致的空间记忆障碍，其作用强于他克林．

双(7)-他克林对非洲爪蟾卵母细胞表达的Kv4．2和Kv1．2编码钾通道的作用

目的用非洲爪蟾卵母细胞表达之Kv4.2和Kv1.2编码的快和慢钾通道,检验双(7)-他克林对此两种通道是否有抑制作用。方法应用爪蟾卵母细胞注射mRNA进行表达,电压钳记录Kv4.2和Kv1.2钾电流(IK)。结果双(7)-他克林抑制IK(Kv4.2)和IK(Kv1.2)的IC50值分别为(0.23±0.05)μmol/L和(0.24±0.06)μmol/L。结论此种抑制效应可能与在双(7)-他克林作用下表达的Kv4.2和Kv1.2钾通道激活曲线向超极化电压方向偏移有关。

双(7)他克林对大鼠海马缺血性损伤的保护作用

目的:研究双(7)他克林对大鼠缺血性脑损伤中海马神经元损伤的作用.方法:永久性结扎大鼠双侧颈总动脉建立老年性痴呆模型,手术动物随机分成2组,手术7 d后分别给以双(7)他克林和生理盐水灌胃,给药7d后灌注固定处死动物,取海马组织,常规脱水包埋,连续切片.分别进行常规HE染色、凋亡检测、PCNA及GFAP免疫组织化学染色.在海马CA1区、CA2区、CA3区和齿状回区取凋亡细胞及PCNA、GFAP阳性细胞进行连续图片采集后计数.结果:经双(7)他克林治疗7d后,大鼠海马区颗粒细胞层细胞凋亡现象有不同程度的降低,CA1区、CA3区和齿状回区更为明显(P值:0.03,0.00,0.03);PCNA阳性细胞出现明显增多(P值:0.00,0.03,0.00,0.00);颗粒细胞层细胞出现不同程度增多,胶质细胞的密度增加,星形细胞的胞质突起增多,以CA1区最为明显(P值:0.04).结论:双(7)他克林在大鼠海马早期缺血性损伤时不仅具有抗凋亡的作用,还具有激活大脑自身修复机制的双重效应,还可能通过促进星形胶质细胞的增生以及形态结构的改变,减轻神经细胞的凋亡而实现对海马神经元的保护作用.

老龄鼠慢性脑缺血后B7T促神经发生与认知改善的相关分析

目的观察B7T对慢性脑缺血老龄大鼠学习记忆和神经发生的干预作用。方法将36只12月龄雄性SD大鼠随机分为2VO—B7T组、2VO—saline组和Sham—saline组，每组12只。构建慢性脑缺血的2VO模型，假手术组不结扎血管。造模6个月后，给予B7T或生理盐水干预，采用Morris水迷宫实验检测学习记忆功能，采用Br-du标记新生神经细胞并计数。结果定位航行实验显示，2VO—saline组大鼠逃逸时间明显长于2VO—B7T组（P〈0．05）和Sham—saline组（P〈0．01）；空间探索实验显示，2VO—saline组大鼠停留平台所在象限时间和跨越平台所在区域次数明显少于2VO—B7T组（P〈O．05）和Sham—saline组（P〈0．01）。免疫组化染色显示，大鼠齿状回BrdU阳性细胞数目2VO—saline组较Sham—saline组增多（P〈0．05），2VO—BTT组较2VO—Saline组显著增多（P〈0．01）。各组齿状回BrdU阳性细胞数量和记忆改善呈正相关（P〈0．05）。结论慢性脑缺血可致老龄大鼠认知功能损伤，B7T改善认知障碍与其促神经发生密切相关。

乙醇基溶胶-凝胶法制备BNKLT无铅压电薄膜

以乙醇作溶剂,氧化物和碳酸盐为原料,利用溶胶-凝胶法制备了Bi0.5(Na0.7K0.2Li0.1)TiO3(BNKLT)无铅压电薄膜。通过红外光谱(IR)、同步热分析仪(TG-DSC)、X线衍射仪(XRD)及扫描电子显微镜(SEM)等分析了乙醇基溶胶-凝胶法制备BNKLT压电薄膜的工艺参数。结果表明,乙酰丙酮与Ti(OC4H9)4的物质的量比(N)≥1.0时,反应温度4060℃,pH=2.02.5,能获得稳定性良好的乙醇基溶胶;采用旋涂法制备的湿膜在600℃热处理30min后,可得表面光亮平整,厚度均一,致密性良好,单一钙钛矿结构的BNKLT无铅压电薄膜。

乙醇基溶胶-凝胶法制备BNKLT粉体及压电陶瓷

以乙醇为溶剂,氧化物和碳酸盐为原料,采用溶胶-凝胶(Sol-Gel)法制备了Bi0.5(Na0.7K0.2Li0.1)TiO3(BNKLT)纳米粉体和无铅压电陶瓷。利用IR,TG-DSC,XRD,SEM等测试技术研究了乙醇基Sol-Gel法制备BNKLT纳米粉体及无铅压电陶瓷的工艺参数。实验表明,乙酰丙酮与钛酸四丁酯的摩尔比N≥1.0时,反应温度60℃,pH=2.0～2.5时,能制备出稳定性良好的乙醇基溶胶,凝胶在600℃内预烧即可获得单一钙钛矿结构的BNKLT纳米粉体,晶粒大小约20nm,并于1 050℃条件下烧结出致密度较高的陶瓷。性能测试表明,该方法制备的压电陶瓷俱有优良的电学性能:压电常数d33=192pC/N,机电耦合系数kp=0.32,介电常数εr=1 096,介电损耗tanδ=0.039,品质因数Qm=79。

Improved stability of blue TADF organic electroluminescent diodes via OXD-7 based mixed host

Thermally activated delayed fluorescence(TADF)organic light-emitting diodes(OLEDs)have been demonstrated in applications such as displays and solid-state lightings.However,weak stability and ineffi-cient emission of blue TADF OLEDs are two key bottlenecks limiting the development of solution processable displays and white light sources.This work presents a solution-processed OLED using a blue-emitting TADF small molecule bis[4-(9,9-dimethyl-9,10-dihydroacridine)phenyl]sulfone(DMAC-DPS)as an emitter.We comparatively investigated the effects of single host poly(Nvinylcarbazole)(PVK)and a co-host of 60%PVK and 30%2,2′-(1,3-phenylene)-bis[5-(4-tert-butylphenyl)-1,3,4-oxadiazole](OXD-7)on the device performance(the last 10%is emitter DMAC-DPS).The co-host device shows lower turn-on voltage,similar maximum luminance,and much slower external quantum efficiency(EQE)rolloff.In other words,device stability improved by doping OXD-7 into PVK,and the device impedance simultaneously and significantly reduced from 8.6103 to 4.2103 W at 1000 Hz.Finally,the electroluminescent stability of the co-host device was significantly enhanced by adjusting the annealing temperature.

双(7)-他克林对慢性脑缺血老龄大鼠海马神经损伤及认知障碍的改善作用

目的:探讨双(7)-他克林[(bis(7-)tacrine,B7T)]对慢性脑缺血老龄大鼠认知障碍及海马锥体细胞的保护作用,并分析其促神经细胞增生与认知功能改善的相关性。方法:采用安全随机法将45只12月龄雄性SD大鼠分为缺血组、对照组和干预组,每组15只。采用水迷宫实验评估大鼠学习记忆等认知功能,免疫组化及荧光染色后对海马CA1区锥体细胞、凋亡细胞进行计数。结果:行为学水迷宫实验显示:缺血组整体逃逸时间明显长于对照组和干预组(P<0.01);缺血组停留于平台所在象限的时间明显少于对照组和干预组(P<0.05);缺血组跨过平台区域的次数显著少于对照组(P<0.01)和干预组(P<0.05)。免疫组化染色显示:缺血组海马CA1区NeuN阳性细胞明显少于对照组(P<0.01)和干预组(P<0.05)。荧光染色显示:缺血组凋亡细胞明显多于对照组(P<0.01)和干预组(P<0.05)。认知改善与锥体细胞增生、凋亡抑制的相关性分析:缺血组、对照组及干预组海马CA1区锥体细胞数量、凋亡细胞数量变化分别与空间记忆功能改善呈正相关、负相关。结论:慢性脑缺血后老龄大鼠学习记忆能力受损,B7T可通过促进海马锥体细胞增生、抑制细胞凋亡,实现对认知功能障碍的改善作用。

双他克林对原代培养小鼠星形胶质细胞缺氧缺糖损伤的保护作用

目的 :研究一种新的乙酰胆碱酯酶抑制剂双他克林在缺氧、缺糖诱导的细胞坏死和细胞凋亡中的作用。方法 :用缺氧和缺糖来诱导原代培养的小鼠大脑皮层星形胶质细胞损伤 ,通过测定 L DH释放量观察细胞存活率 ;相差显微镜和 Hoechst 33342染色观察细胞和核形态 ,并计数核固缩的细胞数量。结果 :缺氧、缺糖 6 h后约 6 0～ 70 %的细胞发生凋亡 ,使用双他克林 (1- 10 n M)可有效抑制缺氧、缺糖诱导的细胞凋亡 ,从形态学和生化检测两方面均可证实这一结果。结论 :双他克要可保护星形胶质细胞免受缺氧、缺糖性损伤。提示除了 AD外 。

双(7)-他克林、美金刚和他克林对脑缺血大鼠认知功能及海马神经发生的影响比较

目的:比较双(7)-他克林[bis(7)-tacrine,B7T]、美金刚(memantine)和他克林(tacrine)对慢性脑缺血大鼠认知功能及海马神经发生的影响。方法:将2月龄雄性SD大鼠用完全随机法分为2VO-NS组(n=6)、2VO-B7T组(n=7)2VO-Tacrine组(n=7)、2VO-Memantine组(n=8)和Sham-NS组(n=7)。采用水迷宫实验评估大鼠学习记忆等认知功能,免疫荧光双标染色对新生神经细胞进行计数。结果:水迷宫实验显示:2VO-NS组的整体逃逸时间明显高于Sham-NS组(P<0.01);给予B7T、他克林和美金刚干预后脑缺血大鼠的空间学习记忆能力较2VO-NS组均有改善(P<0.01);2VO-NS组大鼠停留于目标象限的时间及穿过平台的次数较Sham-NS组明显减少(P<0.01)。给予B7T、他克林和美金刚干预后大鼠在目标象限的停留时间较2VO-NS组显著增多(P<0.01,P<0.05和P<0.01),B7T、他克林和美金刚干预后大鼠穿过平台的次数明显多于2VO-NS组(P<0.01,P>0.05和P<0.05)。免疫荧光双标实验结果显示:2VO-NS组大鼠海马齿状回BrdU和NeuN双染细胞数量较Sham-NS组增多,P<0.01。干预后各组大鼠海马齿状回中新生神经细胞的数量较2VO-NS组增多(P<0.01VS.2VO-B7T;P>0.05 VS.2VO-Tacrine;P<0.05 VS.2VO-Memantine)。大鼠在目的象限游行的时间及跨过平台区域的次数与新生神经细胞数量呈正相关,P<0.05。结论:慢性脑缺血可以导致大鼠认知功能障碍和神经发生增强,给予B7T干预后大鼠空间学习记忆能力得到改善,且效果优于他克林和美金刚,海马齿状回神经发生增强可能是认知功能改善的基础。

双七他克林对青光眼模型大鼠视神经的保护作用

目的:观察双七他克林对青光眼模型大鼠的视神经保护作用。方法:选取雄性成年SD大鼠24只,随机分成对照组、手术组、双七他克林组和美金刚胺组,通过右眼巩膜上静脉注射高渗盐水(对照组大鼠右眼仅进行上巩膜静脉穿刺)制作青光眼模型后,对照组和手术组大鼠给予正常饮水,双七他克林组和美金刚胺组大鼠饮用水中每天分别添加0.5mg/kg双七他克林和5mg/kg美金刚胺,持续5wk。定期测量眼压,造模后5wk处死大鼠,取右侧视网膜进行免疫荧光染色,检测视网膜神经节细胞数目和视网膜神经纤维层厚度。结果:造模后模型大鼠右眼眼压均显著升高,至造模后1mo,均高于28mmHg。手术组大鼠右眼视网膜神经节细胞数较对照组明显减少(79.83±9.58个vs 119.50±8.26个,P<0.01),神经纤维层厚度明显变薄(6.64±0.50μm vs 13.40±0.60μm,P<0.01),而双七他克林(109.00±7.04个)和美金刚胺(107.33±8.57个)能够抑制青光眼所致的视网膜神经节细胞减少,且双七他克林能够抑制青光眼所致的视网膜神经纤维层萎缩(12.26±0.78μm)。结论:双七他克林能够抑制青光眼所致视网膜神经节细胞数目减少及神经纤维层萎缩。