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1.
目的:探讨督脉电针与神经干细胞移植联合应用对大鼠脊髓全横断损伤的前角运动神经元存活以及减轻后肢肌萎缩有无促进作用。方法:将正常组、对照组、督脉电针组(电针组)、神经干细胞移植组(NSCs组)和督脉电针+神经干细胞移植组(电针NSCs组)成年大鼠T10脊髓段做全横断损伤,其中NSCs组和电针NSCs组在损伤处移植神经干细胞,电针组和电针NSCs组在术后开始接受督脉电针治疗。所有实验动物在脊髓损伤后存活65天。结果:电针NSCs组大鼠其腰段脊髓受损伤运动神经元的存活数量明显多于其他实验对照组大鼠。电针NSCs组大鼠后肢的股二头肌萎缩程度明显小于其他实验对照组大鼠。结论:督脉电针与神经干细胞移植联合应用能够促进大鼠脊髓全横断损伤后受损伤的脊髓前角运动神经元存活,以及减轻大鼠脊髓全横断损伤后瘫痪的后肢股二头肌的萎缩状况。  相似文献   

2.
目的:探讨神经营养素-3 (NT-3) 基因修饰雪旺细胞(SCs)和神经营养素-3受体 (TrkC) 基因修饰骨髓间充质干细胞(MSCs)联合移植对全横断脊髓损伤(SCI)大鼠的大脑皮质感觉运动区、红核和背核受损伤神经元存活的影响,为细胞治疗和基因治疗的临床应用提供依据。方法:将含有NT-3-SCs和TrkC-MSCs的PLGA高分子支架移植到大鼠脊髓全横断损伤处。在术后第67天,取其大脑和脊髓进行冷冻切片。用免疫荧光组织化学染色方法,检测SCI处SCs和MSCs的存活及其外源性基因的表达,并计算大脑皮质感觉运动区内锥体细胞层、中脑红核和L1脊髓背核的神经元数量。结果:2个月后,可见SCI处有移植的SCs和MSCs,其中转染的外源性基因NT-3和TrkC可在移植细胞内表达。NT-3-SCs+TrkC-MSCs移植组大脑皮质感觉运动区内锥体细胞层、中脑红核和L1脊髓背核的神经元数量明显高于其他组。 结论:NT-3基因修饰SCs和TrkC基因修饰MSCs联合移植能够促进全横断SCI大鼠的大脑皮质感觉运动区、中脑红核和脊髓背核受损伤神经元的存活。  相似文献   

3.
目的:探讨神经干细胞(NSCs)与神经营养素-3(NT-3)基因修饰雪旺细胞(SCs)联合移植对全横断脊髓损伤大鼠的后肢运动及神经传导功能修复的作用。方法:将:NSCs与NT-3基因修饰SCs或未基因修饰SCs联合移植,或NSCs单独移植到大鼠全横断性脊髓损伤处,60d后进行爬网格测验和BBB评分检测运动功能。第67d,进行皮质运动诱发电位(CMEP)和皮质感觉诱发电位(CSEP)检测脊髓的神经传导功能。结果:脊髓损伤大鼠后肢的运动功能及CMEP和CSEP的修复程度依次为NSCs与NT-3基因修饰SCs联合移植组,NSCs与未基因修饰SCs联合移植组,NSCs单独移植组和实验对照组。结论:NSCs与NT-3基因修饰SCs联合移植能够促进脊髓损伤后大鼠的后肢运动及神经传导功能的修复。  相似文献   

4.
目的:探讨高压氧(HBO)对大鼠脊髓全横断损伤后移植的神经干细胞存活、增殖及分化的影响。方法:成年健康SD大鼠20只,随机分为神经干细胞移植组(NSCs组)和HBO联合神经干细胞移植组(HBO+NSCs组)各10只。2组均采用脊髓全横断损伤模型,术后均给予NSCs移植治疗,HBO+NSCs组在移植后辅以HBO治疗。治疗后检测移植在脊髓损伤处的神经干细胞存活、增殖及分化的情况。结果:术后第28d,HBO+NSCs组移植的神经干细胞存活数量显著多于NSCs组(P〈0.05)。2组大鼠的脊髓损伤处及其相邻的组织均可观察到较多移植的神经干细胞分化为胶质纤维酸性蛋白(GFAP)阳性染色细胞。HBO+NSCs组中移植的神经干细胞分化为神经元特异性烯醇化酶(NSE)阳性染色细胞百分率显著高于NSCs组(P〈0.05)。结论:HBO能够促进大鼠脊髓损伤处移植的神经干细胞存活、增殖,并能促进这些细胞能分化为NSE阳性神经元。  相似文献   

5.
摘要 目的:研究督脉电针对慢性期脊髓损伤大鼠功能康复及神经营养因子的表达的影响,探讨督脉经上不同穴位电针的作用是否存在差异。 方法:将32只雄性SD大鼠随机分为4组:假模组、模型对照组、头部督脉电针组(“百会、风府”)、背部督脉电针组(“大椎、命门”),每组8只。建立大鼠脊髓损伤模型,各治疗组于术后1周开始6周的电针治疗。采用BBB运动功能评分法评定大鼠后肢运动功能的恢复情况。术后7周处死大鼠,采用实时荧光定量PCR及Western-blot方法检测受损脊髓脑源性神经营养因子(BDNF)、神经营养素-3(NT-3)mRNA和蛋白的表达。 结果:电针干预组BBB评分高于模型组(P<0.05),且背部督脉电针组评分明显高于头部督脉电针组(P<0.05)。电针治疗后大鼠脊髓BDNF及NT-3 mRNA和蛋白的表达与模型对照组比较均明显上调(均P<0.05),且背部督脉电针组高于头部督脉电针组(P<0.05)。 结论:电针治疗能增强受损伤脊髓神经营养因子的表达和促进大鼠后肢运动功能的恢复,背部督脉电针组作用强于头部督脉电针组。  相似文献   

6.
目的 探索电针治疗慢性脊髓损伤的作用机理.方法 采用大鼠后路渐进性脊髓压迫动物模型,然后手术减压,并进行电针治疗.通过体诱发电位和BBB评分观察后肢功能,采用免疫组化和蛋白印迹法观察神经营养因子-3 (NT-3)及其受体(TrkC)的变化.结果 脊髓损伤后NT-3和TrkC在神经元及胶质细胞表达增强,经过电针治疗后, NT-3和TrkC在神经元和胶质细胞的表达下降.诱发电位检测和BBB评分显示,电针组疗效优于减压组(P〈0.05).结论 电针治疗可促进脊髓损伤大鼠的行为功能恢复,这可能是通过内源性神经营养因子及其受体介导的.  相似文献   

7.
背景:研究表明,脐血干细胞移植对脊髓损伤的恢复起促进作用,而电针也能够通过抑制星形胶质细胞增生,来减少损伤部瘢痕形成,故推测两者结合可能在急性脊髓损伤治疗中发挥重要作用。目的:观察人脐血干细胞局部移植联合督脉电针治疗后大鼠脊髓损伤组织神经生长因子、神经营养因子3的表达。方法:选取雌性SD大鼠72只,随机分为对照组、损伤组、移植组、联合组。对照组单纯性背部切口后缝合,损伤组脊髓横断处(T 10结果与结论:脊髓损伤后,移植组与损伤组相比,联合组与移植组相比,神经生长因子、神经营养因子3在7,14,28 d表达量均增加(P<0.05)。Western Blot、实时荧光定量PCR与免疫组化结果相一致。结果显示人脐血干细胞移植与电针联合治疗脊髓损伤具有协同作用,显著上调损伤脊髓神经生长因子、神经营养因子3的表达水平,有利于脊髓损伤后功能恢复。水平)放置约1 mm×2 mm×2 mm大小、浸润生理盐水的明胶海绵;移植组及联合组在脊髓横断处放置浸润人脐血干细胞悬液的明胶海绵,联合组于造模后1 h开始给予督脉电针治疗。在相应处理7,14,28 d后应用免疫组织化学、Western Blot及实时荧光定量PCR方法检测脊髓组织神经生长因子、神经营养因子3表达量的变化。  相似文献   

8.
背景:电针在脊髓损伤的康复过程中有其一定的临床作用,同时以嗅鞘细胞为代表的细胞治疗在部分患者的康复过程中亦起到了一定的作用,两者是否具有协同应用尚不清楚。目的:观察督脉电针联合嗅鞘细胞移植对前脊髓综合征大鼠神经营养因子3水平及P75NTR表达的影响。方法:将40只成年大鼠随机分为对照组、督脉电针组、嗅鞘细胞移植组、督脉电针+嗅鞘细胞移植组,经嗅鞘细胞移植和督脉电针治疗2周后ELISA法检测脊髓组织神经营养因子3水平,免疫组化检测P75NTR的表达。结果与结论:督脉电针+嗅鞘细胞移植组神经营养因子3水平较对照组及其他实验组高(P〈0.05);嗅鞘细胞移植组和督脉电针+嗅鞘细胞移植组的脊髓损伤部位以及相邻的组织内均有P75NTR表达,且督脉电针+嗅鞘细胞移植组阳性表达明显较嗅鞘细胞移植组多。实验证实督脉电针联合嗅鞘细胞移植能够明显增高大鼠前脊髓综合征邻近组织的神经营养因子3水平;督脉电针可以有效促进移植的嗅鞘细胞在宿主内存活。  相似文献   

9.
背景:5-羟色胺能纤维可以作为评价脊髓损伤后再生的指标之一。目的:观察神经干细胞在脊髓损伤的亚急性期(第7天)脊髓内移植对大鼠受损伤脊髓再生修复的影响。方法:将正常成年SD雌性大鼠分为3组,单纯脊髓全横断组、假手术组(仅仅打开椎板,但不横断脊髓)、神经干细胞移植组。神经干细胞移植组在脊髓全横断后第7天时进行神经干细胞移植,其他两组不移植神经干细胞。结果与结论:神经干细胞移植组瘢痕上1至2节段5-羟色胺的阳性纤维数量多于单纯脊髓全横断组。提示神经干细胞亚急性期移植能部分促进脊髓损伤后脊髓神经的再生。  相似文献   

10.
目的:探讨神经营养素-3(NT-3)基因修饰骨髓间充质干细胞(MSCs)的明胶海绵圆柱体支架移植对大鼠全横断脊髓损伤部分结构和功能修复的影响。方法:选取15只SD大鼠,随机分成3组:①NT-3基因修饰MSCs联合明胶海绵圆柱体支架移植组(NT-3-MSCs组);②MSCs联合明胶海绵圆柱体支架移植组(MSCs组);③单纯明胶海绵圆柱体支架移植组(control组)。在脊髓全横断后施行上述支架移植,在一定时间点比较3组动物功能恢复情况及其脊髓损伤区的结构变化。结果:NT-3-MSCs组BBB功能评分、移植的MSCs存活数、神经丝蛋白-200(NF-200)阳性纤维计数和平均空洞面积均优于其余组别(P<0.05)。结论:NT-3基因修饰MSCs联合明胶海绵圆柱体支架移植能够促进大鼠脊髓损伤部分结构和功能的修复,为临床治疗脊髓损伤提供实验依据。  相似文献   

11.
3-Deazaguanine (ICN 4221), 3-deazaguanosine (ICN 4793), and 3-deazaguanylic acid (ICN 5412) represent a new class of synthetic guanine analogs having antiviral activity. In vitro, nine ribonucleic acid and seven deoxyribonucleic acid viruses were inhibited, including influenza, parainfluenza, rhino-, vesicular stomatitis, adeno-, herpes-, cytomegalo-, vaccinia, pseudorabies, and myxoma viruses. They were effective orally against influenza types A and B and parainfluenza type 1 (Sendai) virus infections in mice, with a therapeutic index of 16 against the latter two viruses. The course of herpes encephalitis was altered only when the drugs were applied directly into the brain. In addition, these drugs were effective inhibitors of Friend leukemia virus-induced splenomegaly in mice; treatment also produced extensions of life in these animals.  相似文献   

12.
背景:聚羟基丁酸-羟基异戊酯是微生物在生长条件不平衡状态时合成的产物,具有可降解性、热塑性,作为组织工程的新犁支架材料,越来越受到重视.目的:评估聚羟基丁酸-羟基异戊酯作为组织工程支架,与绵羊关节软骨细胞的相容性.设计、时间及地点:体外埘比观察实验,于2005-11/2007-05在中山大学附属第三医院中心实验室和广东冠吴生物科技公司动物手术室完成.材料:聚羟基丁酸-羟基异戊酯膜和泡沫样三维支架由华南理工大学材料学院提供.6月龄雄性实验绵羊1只,体质量17kg,由广东冠吴生物科技公司提供.方法:切取绵羊膝关节软骨后,分离、原代培养软骨细胞,将第2代软骨细胞接种至聚羟基丁酸-羟基异戊酯膜和泡沫样三维支架上,以单纯细胞培养为对照.主要观察指标:扫描电镜观察细胞形态,计数1,2,6 h时的细胞黏附率:按培养液量与支架体积10 mL/cm3为标准浓度制备浸提液,并制备标准浓度1/16~16倍的浸提液,以MTT法检测细胞毒性;流式细胞仪分析接种到材料上的细胞周期,计算增殖指数;接种于聚羟基丁酸-羟基异戊酯二维支架上4,8,12 d,以Hoechst33258荧光法定量测定细胞内DNA含量,二甲基亚甲蓝法测定糖胺聚糖含量.结果:第2代软骨细胞在聚羟基丁酸-羟基异戊酯膜上6 h的黏附率75.6%,与对照组比较差异无显著性;9个浓度梯度的浸提液毒性均为O级;扫描电镜观察见细胞在聚羟基丁酸-羟基异戊酯膜上伸展良好,形态佳,细胞间连接正常,在三维支架的孔隙内立体生长,并分泌大量基质;流式细胞分析接种于材料上的细胞周期无变化;与培养瓶内软骨细胞相比,8d时,聚羟基丁酸-羟基异戊酯三维支架上的细胞内牯胺聚糖浓度显著增高,12 d时,支架上的细胞内DNA量显著增高.结论:聚羟基丁酸-羟基异戊酯作为软骨组织工程支架材料,与绵羊关节软骨细胞具有良好的生物相容性,但早期细胞黏附率低,是其小足.  相似文献   

13.
Concentrations of 3'-fluoro-3'-deoxythymidine (FDT) and 3'-deoxy-2',3'-didehydrothymidine (D4T) in plasma declined in a biexponential fashion. Total clearance of D4T (1.75 +/- 0.22 liters/h/kg; mean +/- standard deviation) was significantly greater than that of FDT (1.19 +/- 0.19 liters/h/kg) owing to greater renal and nonrenal clearances of the former. Steady-state volumes of distribution of FDT (1.20 +/- 0.12 liters/kg) and D4T (1.07 +/- 0.15 liters/kg) were similar.  相似文献   

14.
目的:探讨凋亡信号分子CASP3、C-CASP3在肺癌与癌旁中的表达差异及其与临床参数的关系意义。方法:制备非小细胞肺癌患者的癌与癌旁组织石蜡标本的组织芯片。采用免疫组织化学方法检测分析CASP3、C-CASP3凋亡分子在组织中的蛋白表达水平。结果:非配对的癌(n=139)与癌旁组织(n=25)中凋亡相关分子表达水平:非参数秩和检验结果提示CASP3、C-CASP3两组间比较发现在癌组织均有显著性差异的升高表达(P<0.01);双变量相关分析显示CASP3与C-CASP3之间相关性存在统计学显著性意义。凋亡分子表达与临床病理、生存因素之间的关系:C-CASP3在非鳞癌中表达高于鳞癌(P<0.05);KaplanMeir生存曲线法分析提示Ⅰ~Ⅱ期患者中CASP3表达水平与PFS存在负相关趋势(P=0.094)。结论:肺癌组织较癌旁组织凋亡分子表达均上调,CASP3可能成为可进行药物干预的分子标志物和靶点。C-CASP3在非鳞癌中表达高于鳞癌,在非鳞癌组织类型亚群患者中CASP3更可能作为潜在的干预靶点激活为C-CASP3而促进肿瘤细胞凋亡。CASP3可能是PFS的独立预后因子。  相似文献   

15.
3'-Fluoro-3'-deoxythymidine and 3'-deoxy-2',3'-didehydrothymidine are nucleoside analogs which inhibit human and simian immunodeficiency virus in vitro. The pharmacokinetic properties of these compounds in rhesus monkeys after intravenous, oral, and subcutaneous administration of the drug were compared. Half-lives, total clearances, and steady-state volumes of distribution of the two drugs were determined. The half-lives for the drugs by the different routes were between 0.58 and 1.4 h. Oral bioavailability of 3'-deoxy-2',3'-didehydrothymidine was incomplete, with an average of 42% +/- 15% of the dose reaching the systemic circulation. Absorption of 3'-fluoro-3'-deoxythymidine after oral administration was variable, with bioavailability ranging from 21 to 95%. Bioavailability after subcutaneous administration ranged from 59 to 77% for 3'-deoxy-2',3'-didehydrothymidine and from 52 to 59% for 3'-fluoro-3'-deoxythymidine. The ratio of concentrations in cerebrospinal fluid and serum for the drugs was about 0.15 at 1 h after drug administration and was independent of the route of administration, suggesting that a nucleoside carrier-mediated process is involved in the transport of these compounds to the central nervous system. Because of the similar metabolism of nucleoside analogs in monkeys and humans, the potential glucuronide formation was assessed. Whereas the glucuronide of 3'-fluoro-3'-deoxythymidine was readily detected in urine, the amount of 3'-deoxy-2',3'-didehydrothymidine glucuronidated was small or not detectable in one-half of the urine samples. Pharmacokinetic parameters for the two drugs were similar to each other and analogous to those for 3'-azido-3'-deoxythymidine in monkeys, suggesting that the same dose and scheduling of the drug can be used for all three compounds in prophylactic and therapeutic efficacy drug studies in rhesus monkeys.  相似文献   

16.
3'-Fluoro-3'-deoxythymidine (FLT), a candidate anti-AIDS compound in clinical trials, showed anti-human immunodeficiency virus type 1 (HIV-1) potency (50% effective concentration, 0.0052 microM) slightly better than or equal to that of 3'-azido-3'-deoxythymidine (AZT) in MT4 cells and was threefold more potent in H9 cells. There was no FLT resistance demonstrable in the AZT-resistant HIV-1 strains. Both FLT and AZT showed low cytotoxicity for MT4 cells, with selectivity indices (efficacy/toxicity ratio) of greater than 47,000 and greater than 33,000, respectively. Cellular permeation of FLT and thymidine (dThd) was greater than that of AZT, and FLT and dThd permeated the cell membranes by a carrier-mediated mechanism as well as by simple diffusion, as indicated by the existence of nitrobenzylthioinosine-5'-monophosphate-sensitive and -insensitive components. By contrast, transport of AZT into cells was by simple diffusion. The intracellular level of the triphosphate of FLT (FLTTP) in MT4 cells was two- to threefold higher than that of AZT (AZTTP) after exposure to 1.8 microM each compound for 12 h. The elimination kinetics of FLTTP and AZTTP in HIV-1-infected MT4 cells in fresh medium showed biphasic patterns, with initial half-lives of 1.03 and 1.09 h, respectively. In phytohemagglutinin-stimulated human peripheral blood lymphocytes, the FLTTP level was increased 59-fold compared with that in unstimulated cells at 12 h, was four- to sixfold higher than the level of AZTTP in stimulated cells at 12 h, and remained four- to fivefold higher during a 4-h elimination period in fresh medium and twofold higher at the end of a 12-h elimination period. Two- to eightfold more [3H]AZT than [3H]FLT was incorporated into the host cell DNA, and both [3H]AZT and [3H]FLT remained persistently incorporated for over 24 h. The incorporated [3H]AZT and [3H]FLT were alkali labile, whereas incorporated [3H]dThd was alkali stable. Pharmacokinetics of FLT in plasma of monkeys after intravenous (i.v.) administration showed that the FLT concentration in plasma declined, with a half-life of 1.19 +/- 0.1 h; the steady-state volume of distribution was 0.93 +/- 0.2 liter/kg of body weight, and total clearance was 0.56 +/- 0.15 liter/kg. Oral bioavailability of FLT was excellent and comparable to i.v. bioavailability in terms of areas under the concentration-time curves for three monkeys. Of the total dose, 41 to 61% was excreted in urine as unchanged FLT, and only 3.2 to 7.4% of the total dose was identified as glucuronide-conjugated FLT in urine 48 h after i.v. administration to monkeys. We conclude that FLT exhibits an anti-HIV-1 potency similar to that of AZT but with slightly better selectivity of effects and with higher intracellular active metabolite levels.  相似文献   

17.
Transferrin binding of Al3+ and Fe3+   总被引:6,自引:0,他引:6  
An understanding of Al3+-induced diseases requires identification of the blood carrier of Al3+ to the tissues where Al3+ exerts a toxic action. Quantitative studies demonstrate that the protein transferrin (iron-free) is the strongest Al3+ binder in blood plasma. Under plasma conditions of pH 7.4 and [HCO3-]27 mmol/L, the successive stability constant values for Al3+ binding to transferrin are log K1 = 12.9 and log K2 = 12.3. When the concentration of total Al3+ in plasma is 1 mumol/L, the free Al3+ concentration permitted by transferrin is 10(-14.6) mol/L, less than that allowed by insoluble Al(OH)3, by Al(OH)2H2PO4, or by complexing with citrate. Thus transferrin is the ultimate carrier of Al3+ in the blood. We also used intensity changes produced by metal ion binding to determine the stability constants for Fe3+ binding to transferrin: log K1 = 22.7 and log K2 = 22.1. These constants agree closely with a revision of the reported values obtained by equilibrium dialysis. By comparison with Fe3+ binding, the Al3+ stability constants are weaker than expected; this suggests that the significantly smaller Al3+ ions cannot coordinate to all the transferrin donor atoms available to Fe3+.  相似文献   

18.
NALP3(NACHT-LRR-PYD-containing proteins 3 inflammasome)是NOD样受体(NOD-like receptors,NLRs)蛋白家族中典型代表,有调节机体免疫及调控炎症反应的作用,通过促进多种炎性介质(如IL-1β、IL-6、TNF-α等)释放可增加自身免疫性疾病及非感染性疾病的发生风险,近年来有许多研究表明NALP3炎性体还与肿瘤的发生、逃逸及转移有关,使之成为肿瘤性疾病研究的新热点。本文主要针对NALP3炎性体的结构、激活方式及相关肿瘤疾病做一综述。  相似文献   

19.
Recently, we identified 2-styrylchromones as a new class of antirhinovirus flavonoids with moderate activity against both rhinovirus groups A and B. In order to improve the antiviral effect of the first series of tested 2-styrylchromones, a hydroxy or methoxy group was introduced in position 3 of the chromone ring. Cytotoxicity and antiviral activity of the new synthesized compounds were evaluated in HeLa cell cultures infected with rhinoviruses 1B and 14, selected as representative serotypes for viral groups B and A of human rhinoviruses (HRVs), respectively. These antiviral results compared to those obtained for 3-unsubstituted 2-styrylchromones indicate the greater potency of 3-hydroxy and 3-methoxy derivatives against both serotypes.  相似文献   

20.
Lead halide perovskites are promising semiconductors for various optoelectronic devices working in a wide photo-excitation density regime. However, photo-induced instability, attributed to illumination-activated mobile ions, has been an obstacle to their application. Herein, we use the time evolution of photoluminescence (PL) to investigate the light illumination effects of CH3NH3PbBr3 perovskite films under relatively high excitation (up to 4.5 W cm−2). We demonstrate that continuous illumination can lead to both PL enhancement and PL quenching simultaneously, with their weight ratios depending on the excitation density. The experimental data can be well described and interpreted by considering the coexistence of and competition between the photo-induced annihilation and the formation of long-living filled trap states. Our study may provide in-depth insight into the photo-induced instability of perovskite films and help to improve the performance of perovskite-based optoelectronic devices.

Light illumination with relatively high intensity can result in photoluminescence enhancement and quenching simultaneously in lead halide perovskites.  相似文献   

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