醒脑静联合丁苯肽对脑缺血再灌注损伤后细胞凋亡的影响

目的 观察醒脑静、丁苯酞及二者联合分别对大鼠脑缺血再灌注损伤后神经细胞凋亡及Bcl-2和Bax表达的影响。方法 60只雄性wistar大鼠(250±20)g采用改良线栓法制作脑缺血再灌注损伤模型(Middle cerebral artery occlusion,MCAO),随机分为4组,即模型组、醒脑静组、丁苯酞组、醒脑静联合丁苯酞(联合用药)组,每组又分为6、24、72 h三个亚组; 通过原位末端转移酶标记技术(TUNEL)检测神经细胞凋亡情况,采用免疫组化法观察大鼠脑缺血再灌注各个时间点Bcl-2、Bax的表达水平。结果(1)模型组手术对侧大脑半球偶见凋亡细胞,病灶区可见大量神经细胞凋亡。丁苯酞用药组、醒脑静用药组凋亡细胞数明显减少,醒脑静联合丁苯酞组凋亡细胞数最少(P<0.05);(2)丁苯酞组及联合用药组Bcl-2阳性表达水平较模型组均有提高,联合用药组Bcl-2阳性表达水平在各时间点均最高(P<0.05); 丁苯酞组及联合用药组Bax阳性表达水平较模型组均有降低,联合用药组Bax阳性表达水平最低(P<0.05)。结论(1)醒脑静、丁苯酞及二者联合均可能通过抑制脑缺血再灌注损伤后神经细胞凋亡来实现神经细胞保护作用,其中二者联合效果最佳;(2)丁苯酞可能通过增加脑缺血再灌注损伤大鼠Bcl-2表达,减少Bax表达的方式来减少神经细胞凋亡,从而减轻脑缺血再灌注损伤;(3)醒脑静本身不能对Bcl-2、Bax的表达水平产生影响,但其可能通过增强丁苯酞作用的方式影响Bcl-2、Bax的表达,从而减轻脑缺血再灌注损伤。     

大鼠脑创伤后海马CA3区细胞凋亡及相关基因表达研究

目的研究弥漫性脑损伤后不同时间,大鼠海马CA3区细胞凋亡及相关基因Bcl-2、Bax和Caspase-3蛋白的表达情况,探讨脑创伤后神经细胞凋亡的分子生物学机制.方法应用流式细胞仪和免疫组化法,分别检测脑创伤后不同时间海马CA3区细胞凋亡率及Bcl-2,Bax和Caspase-3基因在蛋白质水平的表达情况.结果脑创伤后海马CA3区存在不同程度细胞凋亡,Bcl-2在脑损伤后表达下降,而Bax和Caspase-3在脑创伤后表达升高;Caspase-3表达的峰值时间(72 h)出现在Bax之后(48 h).结论弥漫性脑损伤后,大鼠海马CA3区存在细胞凋亡及Bcl-2,Bax和Caspase-3的表达变化.Bcl-2/Bax表达比值下降早于Caspase-3的上升,Bcl-2/Bax表达比值改变可能与Caspase-3活化有关,进而启动并加重脑损伤后神经细胞凋亡.     

单一连续应激对大鼠行为学和海马Bcl-2、Bax表达的影响

目的 检测单一连续应激(single prolonged stress,SPS)对大鼠行为学和海马神经细胞Bax、Bcl-2表达的影响.方法 将Wistar大鼠分为对照组和应激组.应激组给予SPS应激,采用旷场实验、拒俘反应实验、Morries水迷宫实验等观察大鼠情感行为改变,采用化学发光法测定血清皮质醇浓度,应用免疫组织化学方法检测海马神经元Bcl-2、Bax的表达.结果 对照组水迷宫实验逃避潜伏期为5.632s±1.065s,应激组为20.762s±3.236s(t=9.932,P＜0.01);对照组血清皮质醇浓度为1.25 μg/dl ±0.12μg/dl,应激组为0.58μg/dl±0.09μg/dl(t=7.340,P＜0.01).应激组海马Bcl-2、Bax表达升高,Bcl-2/Bax上调.结论 SPS应激能使大鼠表现出创伤后应激障碍行为,使海马神经细胞Bcl-2/Bax上凋,这可能与创伤后应激障碍发病机制有关.     

局灶性脑缺血再灌注大鼠海马CA1区神经元凋亡研究

目的 观察大鼠局灶性脑缺血再灌注(ischemia reperfusion,I/R)损伤后海马CA1区神经元凋亡、TUNEL阳性细胞变化,以及凋亡相关蛋白Bcl-2与Bax蛋白的表达情况.方法 将健康雄性SD (Sprague-Dawley)大鼠随机分为假手术组和I/R组,每组再分为缺血再灌注后3、6、12、24、48、72 h亚组.应用免疫组化方法检测再灌注后不同时间点大鼠海马CA1区神经元凋亡基因Bcl-2和Bax蛋白的表达及Bcl-2/Bax比值变化,采用原位细胞凋亡检测(TUNEL)技术检测凋亡阳性细胞数.结果 各组非缺血侧相应区域神经元胞质中Bcl-2均有微弱表达.I/R组缺血侧海马CA1区于再灌注3 h开始出现Bcl-2和Bax蛋白微弱表达,随再灌注时间延长神经元内Bcl-2表达逐渐增强,再灌注24 h后Bcl-2表达达高峰,假手术组与I/R组比较差异有统计学意义(P<0.05).结论 I/R损伤后海马CA1区神经元不仅存在变性坏死,还存在明显的细胞凋亡且细胞凋亡在大鼠I/R损伤中发挥重要作用;I/R可诱导海马CA1区细胞凋亡基因Bcl-2和Bax蛋白表达,且其表达呈一定规律.     

亚低温对大鼠脑创伤后海马区凋亡相关蛋白表达的影响

目的观察亚低温对大鼠创伤性脑损伤(TBI)后海马CA3区细胞凋亡及相关蛋白Bcl-2、Bax及Caspase-3表达的影响,探讨亚低温脑保护的分子生物学机制.方法将大鼠随机分成假手术、单纯脑损伤和脑损伤后亚低温治疗3组,应用改良Marmarou方法制作大鼠TBI模型,分别用流式细胞仪(FCM)和免疫组化法检测各组动物脑海马CA3区细胞凋亡率和Bcl-2、Bax及Caspase-3蛋白的表达.结果与假手术组相比,大鼠TBI后海马CA3区细胞凋亡率及Caspase-3表达增高(P<0.05),Bcl-2/Bax表达比下降(P<0.05).亚低温治疗后,大鼠脑海马CA3区细胞凋亡率及Caspase-3表达较单纯脑损伤组降低(P<0.05),而Bcl-2/Bax表达比升高(P<0.05).结论亚低温对TBI的脑保护作用机制可能与干预伤后凋亡相关基因表达并减少神经细胞凋亡有关.     

普瑞巴林对慢性颞叶癫癎大鼠海马凋亡调控基因的影响

目的通过观察普瑞巴林对匹罗卡品慢性癫癎大鼠海马区Bcl-2和Bax表达的影响,探讨普瑞巴林治疗癫癎的药理学机制及对大鼠海马神经元的抗凋亡作用。方法采用氯化锂-匹罗卡品化学诱导方法建立慢性颞叶癫癎模型。经腹腔注射普瑞巴林40mg(/kg·d)连续治疗3周,免疫组织化学染色和Western blotting法检测不同处理组大鼠海马区Bcl-2和Bax表达变化。结果与生理盐水对照组比较,模型组大鼠海马区Bcl-2和Bax表达水平显著升高(均P=0.000);与模型组比较,普瑞巴林治疗组大鼠海马区Bcl-2表达水平升高、Bax表达水平降低,组间差异具有统计学意义(均P=0.000)。结论新型抗癫癎药物普瑞巴林可通过降低慢性颞叶癫癎大鼠海马区Bax表达、上调Bcl-2表达而抑制细胞凋亡,发挥神经元保护作用。     

西酞普兰对慢性应激大鼠海马CA1和CA3区神经细胞B细胞淋巴瘤/白血病-2及Bcl相关蛋白表达与凋亡的影响

Objective To explore effects of citalopram on preventing neuron apoptosis in CA1 and CA3 regions of hippocampus in chronic stress rats.Methods Forty male Sprague Dawley rats were randomly divided into five groups with eight each group.Stressed rat models were made by forced swimming daily for 4 weeks,and the stressed group wag treated with intragagtric administration of 0.9% sodium chloride,and three experimental groups with different dosage of citalopram.The fifth group was given no treatment as control.The proteins of bcl-2 and bax were detected with immunohistochemistry.Apoptosis cell number and integral optical density in CA1 and CA3 regions were tested and analyzed with terminal deoxynucleotidyl transferage biotin-dUTP nick end labeling(TUNEL)method and Nikon imaging software-BR(NIS-BR).Results The stationary time Wag longer in the stress group[(279±53)s]than the control group[(182 ±35)s],and the three citalopram treatment group[(200±71)s,(159±59)s,(165±54)s].The number of struggling[(20 ±3)times]was less than control group[(24 ±3)times]and the treatment groups[(37 ±16),(32 ±10),(24 ±4)times],and exhaustive time[(38.3 ±5.1)min]longer than control group[(22.9±1.8)min],shorter than treatment groups[(54.4 ±2.9)min,(69.3±17.6)min,(46.4±4.0)min].AlJ tIle differences were statistically significant(P＜0.05 or 0.01).Rats in the stress group showed more apoptotic cells,reduced expression of bcl-2 and increased bax protein expression in CA1 and CA3 regions(P＜0.05 or 0.01)in comparison with control group.Compared to the stressed group,rats in treatment groups showed Iess apoptotic cells,reduced expression of bax and increased bcl-2 protein expression in CA1 and CA3 regions(P＜0.05).Conclusion Long-term stress might cause neuron apoptosis and expression of bcl-2 and bax in CA1 and CA3 region of hippocampus,and citalopram might have prophylactic effects on this process.     

西酞普兰对慢性应激大鼠海马CA1和CA3区神经细胞B细胞淋巴瘤/白血病-2及Bcl相关蛋白表达与凋亡的影响

Objective To explore effects of citalopram on preventing neuron apoptosis in CA1 and CA3 regions of hippocampus in chronic stress rats.Methods Forty male Sprague Dawley rats were randomly divided into five groups with eight each group.Stressed rat models were made by forced swimming daily for 4 weeks,and the stressed group wag treated with intragagtric administration of 0.9% sodium chloride,and three experimental groups with different dosage of citalopram.The fifth group was given no treatment as control.The proteins of bcl-2 and bax were detected with immunohistochemistry.Apoptosis cell number and integral optical density in CA1 and CA3 regions were tested and analyzed with terminal deoxynucleotidyl transferage biotin-dUTP nick end labeling(TUNEL)method and Nikon imaging software-BR(NIS-BR).Results The stationary time Wag longer in the stress group[(279±53)s]than the control group[(182 ±35)s],and the three citalopram treatment group[(200±71)s,(159±59)s,(165±54)s].The number of struggling[(20 ±3)times]was less than control group[(24 ±3)times]and the treatment groups[(37 ±16),(32 ±10),(24 ±4)times],and exhaustive time[(38.3 ±5.1)min]longer than control group[(22.9±1.8)min],shorter than treatment groups[(54.4 ±2.9)min,(69.3±17.6)min,(46.4±4.0)min].AlJ tIle differences were statistically significant(P＜0.05 or 0.01).Rats in the stress group showed more apoptotic cells,reduced expression of bcl-2 and increased bax protein expression in CA1 and CA3 regions(P＜0.05 or 0.01)in comparison with control group.Compared to the stressed group,rats in treatment groups showed Iess apoptotic cells,reduced expression of bax and increased bcl-2 protein expression in CA1 and CA3 regions(P＜0.05).Conclusion Long-term stress might cause neuron apoptosis and expression of bcl-2 and bax in CA1 and CA3 region of hippocampus,and citalopram might have prophylactic effects on this process.     

西酞普兰对慢性应激大鼠海马CA1和CA3区神经细胞B细胞淋巴瘤/白血病-2及Bcl相关蛋白表达与凋亡的影响

Objective To explore effects of citalopram on preventing neuron apoptosis in CA1 and CA3 regions of hippocampus in chronic stress rats.Methods Forty male Sprague Dawley rats were randomly divided into five groups with eight each group.Stressed rat models were made by forced swimming daily for 4 weeks,and the stressed group wag treated with intragagtric administration of 0.9% sodium chloride,and three experimental groups with different dosage of citalopram.The fifth group was given no treatment as control.The proteins of bcl-2 and bax were detected with immunohistochemistry.Apoptosis cell number and integral optical density in CA1 and CA3 regions were tested and analyzed with terminal deoxynucleotidyl transferage biotin-dUTP nick end labeling(TUNEL)method and Nikon imaging software-BR(NIS-BR).Results The stationary time Wag longer in the stress group[(279±53)s]than the control group[(182 ±35)s],and the three citalopram treatment group[(200±71)s,(159±59)s,(165±54)s].The number of struggling[(20 ±3)times]was less than control group[(24 ±3)times]and the treatment groups[(37 ±16),(32 ±10),(24 ±4)times],and exhaustive time[(38.3 ±5.1)min]longer than control group[(22.9±1.8)min],shorter than treatment groups[(54.4 ±2.9)min,(69.3±17.6)min,(46.4±4.0)min].AlJ tIle differences were statistically significant(P＜0.05 or 0.01).Rats in the stress group showed more apoptotic cells,reduced expression of bcl-2 and increased bax protein expression in CA1 and CA3 regions(P＜0.05 or 0.01)in comparison with control group.Compared to the stressed group,rats in treatment groups showed Iess apoptotic cells,reduced expression of bax and increased bcl-2 protein expression in CA1 and CA3 regions(P＜0.05).Conclusion Long-term stress might cause neuron apoptosis and expression of bcl-2 and bax in CA1 and CA3 region of hippocampus,and citalopram might have prophylactic effects on this process.     

西酞普兰对慢性应激大鼠海马CA1和CA3区神经细胞B细胞淋巴瘤/白血病-2及Bcl相关蛋白表达与凋亡的影响

Objective To explore effects of citalopram on preventing neuron apoptosis in CA1 and CA3 regions of hippocampus in chronic stress rats.Methods Forty male Sprague Dawley rats were randomly divided into five groups with eight each group.Stressed rat models were made by forced swimming daily for 4 weeks,and the stressed group wag treated with intragagtric administration of 0.9% sodium chloride,and three experimental groups with different dosage of citalopram.The fifth group was given no treatment as control.The proteins of bcl-2 and bax were detected with immunohistochemistry.Apoptosis cell number and integral optical density in CA1 and CA3 regions were tested and analyzed with terminal deoxynucleotidyl transferage biotin-dUTP nick end labeling(TUNEL)method and Nikon imaging software-BR(NIS-BR).Results The stationary time Wag longer in the stress group[(279±53)s]than the control group[(182 ±35)s],and the three citalopram treatment group[(200±71)s,(159±59)s,(165±54)s].The number of struggling[(20 ±3)times]was less than control group[(24 ±3)times]and the treatment groups[(37 ±16),(32 ±10),(24 ±4)times],and exhaustive time[(38.3 ±5.1)min]longer than control group[(22.9±1.8)min],shorter than treatment groups[(54.4 ±2.9)min,(69.3±17.6)min,(46.4±4.0)min].AlJ tIle differences were statistically significant(P＜0.05 or 0.01).Rats in the stress group showed more apoptotic cells,reduced expression of bcl-2 and increased bax protein expression in CA1 and CA3 regions(P＜0.05 or 0.01)in comparison with control group.Compared to the stressed group,rats in treatment groups showed Iess apoptotic cells,reduced expression of bax and increased bcl-2 protein expression in CA1 and CA3 regions(P＜0.05).Conclusion Long-term stress might cause neuron apoptosis and expression of bcl-2 and bax in CA1 and CA3 region of hippocampus,and citalopram might have prophylactic effects on this process.     

电针及氟西汀对抑郁大鼠行为学及海马神经元凋亡的影响

目的 探究电针及氟西汀对慢性应激抑郁大鼠行为学及海马神经元凋亡的影响.方法 65只Sprague-Dawley雄性大鼠,按随机数字表随机分为空白组、空白电针组、模型组、电针组、氟西汀组,每组13只.慢性应激后进行行为学评价;采用膜联蛋白V-异硫氰酸荧光素/碘化丙啶双染法检测海马神经元凋亡率;采用免疫组织化学方法检测海马bcl-2蛋白表达.结果 模型组大鼠旷场试验水平穿越格数[(1.6±1.3)格]、竖立次数[(0.4 ±0.2)次]、体质量增加量[(34±18)g]均明显低于空白组[分别为(51.1 ±22.3)格、(13.2±4.6)次、(128 ±21)g],P均＜0.05;海马神经元细胞凋亡率[(67±10)%]高于空白组[(53±13)%],P＜0.05;海马组织bcl-2蛋白阳性细胞计数[(28±10)个/mm<'2>]低于空白组[(78±22)个/mm<'2>],P＜0.05.电针组[分别为(39.3 ±14.3)格,(9.6 ±4.1)次,(81±43)g]、氟西汀组[分别为(37.2±15.1)格,(9.3±4.6)次,(80 ±35)g]上述指标均明显高于模型组(P＜0.05);海马神经元细胞凋亡率[电针组(30±9)%,氟西汀组(51±13)%]均低于模型组(P＜0.05);海马组织bcl-2蛋白阳性细胞计数[电针组(56±18)个/mm<'2>,氟西汀组(62±24)个/mm<'2>]均高于模型组(P＜0.05),而电针组与氟西汀组间的差异无统计学意义(P＞0.05).结论 电针和氟西汀可改善抑郁大鼠行为学症状,这种改善与海马细胞凋亡机制有一定相关性.     

托吡酯对戊四氮诱导的癫痫大鼠海马神经元bc1-2、bax基因表达的调控

目的探讨托吡酯对戊四氮癫癎模型大鼠大脑的神经保护作用及可能的机制.方法成年雄性Wistar大鼠54只,随机分为正常对照组(6只);戊四氮组(24只);托吡酯预处理组(24只).癫癎发作后分别于6、12、48 h后处死取脑,进行HE染色和bcl-2、bax免疫组化染色.结果癎性发作后海马HE染色显示;戊四氮组CA1、CA3和DC区神经元变性及坏死较托吡酯预处理组显著.免疫组化染色显示托吡酯预处理组bcl-2 12和48 h在CA1、CA3和DC的表达强于戊四氮组,而bax在上述时段的表达则较戊四氮组弱.结论托吡酯具有一定的神经保护作用,推测可能与其增强大鼠海马神经元bcl-2基因表达,降低bax基因表达有关.     

硫酸镁对大鼠脑弥漫性轴索损伤海马区Bcl-2和Bax蛋白表达影响的研究

目的研究脑弥漫性轴索损伤后神经细胞迟发性死亡的机制,探讨镁离子对大鼠脑弥漫性轴索损伤后神经元的保护作用。方法采用Marmarou方法制备大鼠重度脑弥漫性轴索损伤模型,分为创伤组(n=25)、生理盐水组(n=40)和硫酸镁组(n=40)。硫酸镁组伤后半小时给予25%硫酸镁(750μmol/kg),生理盐水组在相同时间给予等量的生理盐水腹腔注射,于伤后6小时、24小时、3天、5天及7天5个时相点处死。采用HE染色、免疫组织化学技术动态观察大鼠海马区的组织病理改变,Bcl-2和Bax蛋白的表达情况,以及使用硫酸镁干预后对上述表达的影响。结果①Bcl-2蛋白的表达:假手术组大鼠海马区仅见极少量Bcl-2阳性细胞,着色淡。在伤后6小时即有大量的Bcl-2阳性细胞,随时间渐增,24小时达到高峰,3～7天逐渐减少。②Bax蛋白的表达:在DAI后大鼠海马区有大量Bax阳性细胞,在伤后6小时就有所增加,24小时显著增加,3天达到高峰。Bcl-2/Bax值在损伤后随时间逐渐上升。③硫酸镁组中,海马区的Bax表达与对照组相比有所减少,而Bcl-2相应增加,Bcl-2/Bax比值也是上调的,均有统计学意义(P<0.05)。结论大鼠脑弥漫性轴索损伤后,海马区神经元存在有迟发性细胞死亡即凋亡现象。Bax与Bcl-2参与细胞凋亡过程。硫酸镁可通过抑制Bax蛋白,上调Bcl-2蛋白,减少神经细胞凋亡,对促进神经细胞修复和功能重塑有益。     

大鼠液压脑损伤后bcl-2和bax基因的表达分布

目的观察脑损伤后凋亡相关基因bcl-2、bax在脑组织中的表达特点。方法SD大鼠12只,随机分为假手术组(n=4)和液压打击脑损伤组(n=8)。采用侧方液压打击制作颅脑损伤模型,应用免疫组化和原位杂交法及计算机显微图像分析技术,观察SD大鼠脑损伤后12h脑内bcl-2、bax蛋白和mRNA阳性细胞的分布。结果侧方液压打击伤后,bcl-2、bax基因在损伤侧大脑皮质、海马表达明显增强,挫裂伤组织内血肿周边的bcl-2、bax基因表达亦明显增强,阳性细胞表达强度受打击能量和颅内血肿影响而呈梯度分布。结论大鼠侧方液压脑损伤后,bcl-2和bax基因表达受打击能量和颅内血肿的影响,由高到低逐渐递减。这一现象为认识脑损伤后迟发性神经元死亡提供了帮助。     

度洛西汀和氟西汀对抑郁模型大鼠 S100B、ERK1/2－NF－κB 表达的影响

目的：比较度洛西汀和氟西汀对抑郁模型大鼠海马 S100B、ERK1/2－NF－κB 表达的影响.方法慢性轻度不可预知应激刺激法制备54只抑郁症模型大鼠,随机分为非干预组(B 组)、度洛西汀干预组(C 组)、氟西汀干预组(D 组),各18只.另外选取18只大鼠为对照组(A 组).各组灌胃[A组和 B 组(生理盐水),C 组(度洛西汀)、D 组(氟西汀)]28 d 后,应用糖水偏爱试验和旷场试验检测大鼠行为学改变.Western blot 检测各组海马 S100B、ERK1/2和 NF－κB 的表达.结果灌胃28 d 后 B 组糖水消耗率(43±15)％显著较 A、C、D 组低[(63±11)％,(67±6)％,(61±10)％](P ＜0．05). C 和 D组大鼠干预28 d 后旷场试验水平评分、垂直运动评分与潜伏期分别为(70．66±11．53)分和(67．54±10.08)分,(20．32±8．85)分和(21．34±7．46)分,(1．0±0．4)s 和(1．1±0．3)s,与 A 组(71．19±12．08)分,(20．42±8．76)分,(1．01±0．3)s 比较,差异均无统计学意义(P ＞0．05);C、D 组与 B 组比较,水平运动评分和垂直运动评分升高,潜伏期降低.A、C、D 组大鼠海马 S100B、ERK1/2、NF－κB 表达显著高于 B组(P ＜0．05),C 和 D 组差异无统计学意义.结论度洛西汀和氟西汀均能够改善抑郁模型大鼠的行为能力及上调海马 S100B、p－ERK1/2－NFκB 表达水平,但度洛西汀和氟西汀对相关因子表达的影响无差异.     

慢性应激及氟西汀治疗后大鼠海马细胞支架的改变

目的 探讨慢性不可预见性应激及氟西汀治疗后大鼠细胞支架微管系统的动态性变化及其可能机制.方法 将24只大鼠按随机数字表法分为对照组(空白对照+生理盐水)、慢性不可预见性温和应激(CUMS)组(CUMS+生理盐水)和氟西汀组(CUMS+氟西汀),每组8只.对大鼠进行连续21 d CUMS后,氟西汀组给予氟西汀(10 mg/kg)治疗21 d,对照组和CUMS组给予生理盐水.实验结束后进行行为学观察,并使用免疫印迹法(western blot)检测大鼠海马乙酰化微管蛋白(Acet-Tub),酪氨酸化微管蛋白(Tyr-Tub),微管结合蛋白2(MAP-2)及磷酸化微管结合蛋白2(phospho-MAP-2).结果 (1)CUMS组糖水偏好[(55.13±11.80)%],总行程[(2736.59±511.20)cm],运动平均速度[(5.69±1.08)cm/s]及直立次数[(2.50±2.00)次]均低于对照组,差异有统计学意义(P＜0.01);氟西汀组上述指标与对照组比较差异无统计学意义(P＞0.05).(2)CUMS组与对照组相比,Acet-Tub表达升高[(171.84±10.34)%],Tyr-Tub[(62.06±9.24)%]和phospho-MAP-2[(68.81±8.93)%]的表达降低,差异有统计学意义(P均＜0.01),MAP-2的表达与对照组比较无统计学意义(P＞0.05);经氟西汀治疗后,Acet-Tub的表达降低为[(96.18±8.92)%],Tyr-Tub和phospho-MAP-2的表达分别升高为[(95.06±8.00)%]、[(100.60±7.30)%],与对照组比较均无统计学意义(P＞0.05).结论 慢性应激后微管动态性减低,神经可塑性受损,氟西汀可以逆转海马的这些损伤,上述过程可能与微管相关蛋白磷酸化水平的变化有关.     

Influence of age or circadian time on Bcl-2 and Bax mRNA expression in the rat hippocampus after corticosterone exposure

A rapid elevation in the level of endogenous corticosterone (CORT) functions in the stress response associated with the hypothalamus-pituitary-adrenal axis, and it has been well documented that high levels of CORT play neurotoxic roles in the hippocampus. Both aging and the circadian rhythm possibly affect the sensitivity to CORT, although their endogenous modifications in the CORT-mediated events remain unclear. To explore the influence of age or circadian time on hippocampal vulnerability to excess CORT, we examined the relative mRNA expression of bcl-2 and bax in the dentate gyrus (DG) and the CA1 subfield, compared with the CA3 as an internal standard, after acute CORT administration using in situ RT-PCR. Male rats aged 10 weeks (young) or 6 months (adult) were treated with CORT at 0800 or 2000 h. The bcl-2 to bax mRNA ratio in the dentate gyrus (DG) was significantly decreased 2h after CORT exposure in the young rats treated at 0800 or 2000 h. In the adult rats, the treatment with CORT at 0800 h significantly decreased the bcl-2 to bax ratio, whereas the treatment at 2000 h was ineffective; the discrepancy between the treatment time points was apparent in adult rats, but not in young rats. Our results emphasize the importance of circadian time as well as age as a factor influencing the stress paradigm.     

ACEI对肾性高血压大鼠脑缺血再灌注后细胞凋亡的影响

目的观察血管紧张素转化酶抑制剂(ACEI)对肾性高血压大鼠脑缺血再灌注后神经功能和细胞凋亡的影响,探讨ACEI的脑保护机制。方法采用狭窄肾动脉方法建立肾性高血压大鼠模型,随机分依那普利组(A组)和高血压缺血再灌注组(B组);正常血压组分为假手术组(C组)和缺血再灌注组(D组)。用线栓法造成大脑缺血再灌注模型,缺血时间为2h,再灌注时间22h。用免疫组织化学技术检测脑组织bcl-2、bax的表达,TUNEL法检测细胞凋亡。结果(1)脑缺血再灌注后神经功能评分:A组神经功能评分较B组和D组降低(P<0.05,);D组神经功能评分低于B组(P<0.05)。(2)A组与B组和D组比较bcl-2表达明显增多(P<0.05),bax表达显著降低(P<0.05),神经细胞凋亡明显减少(P<0.05);B组与D组比较,bcl-2表达明显降低(P<0.05),bax表达明显增加(P<0.05),而神经细胞凋亡明显增多(P<0.05)。结论ACEI明显改善局灶性脑缺血大鼠的神经功能,减少神经细胞凋亡,上调脑组织bcl-2表达,抑制bax表达,提示对脑缺血再灌注损伤有脑保护作用。     

西酞普兰合并利培酮治疗难治性抑郁症的对照研究

目的探讨西酞普兰合并利培酮治疗难治性抑郁症的安全性和疗效。方法将92例难治性抑郁症患者随机分为两组,研究组采用西酞普兰合并利培酮治疗,对照组单用西酞普兰治疗,两组分别在治疗后第2、4、8、12周末,采用汉密顿抑郁量表（HAND）和临床总体印象量表（CGI）评定疗效,Aaberg抗抑郁剂不良反应量表评定不良反应。结果根据HAMD评分,两组8周末减分率分别为（31．85±12．78）,（19．00±11．88）,两组12周末减分率分别为（48．46±20．75）,（29．54±16．85）,两组间差异均具有显著性意义（P〈0．05）;根据CGI评分,两组8周末评分分别为（2．31±0．95）、（3．15±1．06）,两组12周末评分分别为（2．00±1．00）、（2．92±1．19）,两组间差异具有显著性意义（P〈0．05）;药物不良反应两组间无明显差异（P〉0．05）。结论西酞普兰合并利培酮治疗难治性抑郁症的疗效好,不良反应无明显增加。