垂体腺苷酸环化酶激活肽对大鼠脑缺血再灌注损伤后缺血皮层p-JNK表达及神经细胞凋亡的影响

目的研究活化的c-Jun氨基末端激酶（p-JNK）在大鼠局灶性脑缺血再灌注损伤后的表达和垂体腺苷酸环化酶激活肽（PACAP）的影响、抑制细胞凋亡的机制。方法制成局灶性脑缺血再灌注损伤模型。72只大鼠随机分成假手术组、缺血再灌注对照组、PACAP治疗组。缺血开始时治疗组静脉注射PACAP 2．5μg。再灌注后各时间点处死取脑，进行HE染色、p-JNK免疫组化染色和TUNEL法检测神经元凋亡。结果不同时间点PACAP组神经细胞缺血性损伤较缺血再灌注对照组减轻。缺血再灌注对照组p-JNK分别在2、48h成2次表达高峰，凋亡细胞较多；PACAP组再灌注后pJNK表达下降，凋亡细胞减少。结论PACAP对局灶性脑缺血再灌注损伤有保护作用，可抑制细胞凋亡．部分依赖于其可下调p—JNK表达。     

脑缺血再灌注后血管内皮细胞凋亡及其与Bcl—2表达的关系

目的 探讨大鼠局灶性脑缺血再灌注损伤后血管内皮细胞凋亡及其与Bcl-2蛋白表达的关系。方法 采用原位末端标记法和免疫组化法分别观察脑缺血再灌注2h、6h、12h、24h、2d、3d、7d、14d和21d等时间 点血管内皮细胞凋亡和Bcl-2蛋白的表达。结果 （1）脑缺血再灌注2h在缺血周围区即有凋亡内皮细胞出现,12－24h达高峰,之后逐渐下降,至21d与假手术组已无显著性差异。（2）脑缺血再灌注后2h在缺血周围区内皮细胞Bcl-2开始表达,12－24h达高峰,之后逐渐下降,至14d接近假手术组水平。（3）Bcl-2蛋白表达时相变化与内皮细胞凋亡基本一致。结论 脑缺血再灌注损伤中凋亡是血管内皮细胞的死亡形式之一,Bcl-2蛋白具有抑制缺血再灌注后血管内皮细胞凋亡的作用。     

大鼠局灶性脑缺血再灌注后海马Bcl-2、Bax蛋白的表达

目的 探讨大鼠局灶性脑缺血再灌注后Bcl-2、Bax蛋白在海马表达的变化.方法 线栓法制作大鼠局灶性脑缺血再灌注模型,应用免疫组化染色检测Bcl-2、Bax蛋白表达,应用TUNEL法检测海马区细胞凋亡.结果 缺血再灌注2h后海马神经元Bcl-2、Bax蛋白开始表达,Bcl-2蛋白12h达高峰,Bax蛋白12h～24h达高峰,之后开始下降.再灌注2h后海马凋亡细胞开始表达,随着再灌注时间的延长,其表达不断增加.Bcl-2/ Bax的比率在再灌注开始时升高,再灌注12h达高峰,随后开始下降.结论 凋亡是脑缺血再灌注损伤的重要形式之一,Bcl-2/ Bax的改变与缺血再灌注后海马的神经元存亡有关,缺血再灌注可导致海马神经元凋亡.     

大鼠局灶性脑缺血再灌注后凋亡诱导因子的表达与神经元凋亡的关系

目的 探讨大鼠局灶性脑缺血再灌注后凋亡诱导因子(AIF)的表达变化及与细胞凋亡的关系.方法 将Wistar大鼠分为假手术组(6只)和模型组(30只).模型组大鼠采用线栓法建立大脑中动脉闭塞模型,假手术组大鼠插线较模型组浅,不造成大脑中动脉闭塞.观察假手术组及模型组缺血再灌注后6 h、24 h、48 h、72 h和7 d缺血半暗带AIF的表达,同时利用TUNEL法观察对应区域细胞凋亡的动态变化规律.结果模型组脑缺血再灌注6 h在缺血半暗带区AIF阳性细胞显著增加,再灌注48 h达到高峰[(130.47±11.32)个];各时相点均可见细胞凋亡,凋亡细胞数以再灌注48 h最多f(118.53±11.67)个];各组问比较差异均有统计学意义(JP<0.05).结论 局灶性脑缺血再灌注可致AIF表达增加.并引起细胞凋亡.     

亚低温对局灶性脑缺血再灌注大鼠脑皮质神经元凋亡及存活素、脑源性神经营养因子表达的影响

目的观察亚低温干预对局灶性脑缺血再灌注大鼠脑皮质神经元凋亡及存活累(Survivin)、脑源性神经营养因子(BDNF)表达的影响,探讨Survivin、BDNF在亚低温脑保护机制中的作用。方法采用线栓法制备成年雄性SD大鼠大脑中动脉闭塞(MCAO)局灶性脑缺血再灌注改良模型,将90只大鼠随机分为假手术组、常温缺血组和亚低温缺血组,缺血组分别于缺血3h再灌注3h、6h、12h、24h、48h、72h、7d处死,亚低温缺血组于缺血后10min实施全身亚低温持续3h。进行TUNEL染色及免疫组化染色,检测梗死灶周围皮质神经元凋亡数量和Sur-vivin、BDNF的表达水平。结果 (1)亚低温缺血组和常温缺血组于再灌注6h皮质区均出现TUNEL染色阳性细胞,72h达高峰,随后逐渐减少,两组内相邻时间点比较差异均有统计学意义(P<0.05);在相同时间点亚低温缺血组凋亡细胞数明显少于常温缺血组,两组间比较差异有统计学意义(P<0.05)。(2)亚低温缺血组于再灌注3hSurvivin、BDNF表达有所增加,BDNF于24h达高峰,Survivin于48h达高峰,随后表达逐渐降低,但7d时仍高于假手术组,常温缺血组表达趋势与之相似,两组各时间点Survivin、BDNF表达均高于假手术组,差异有统计学意义(P<0.05);除再灌注3h Survivin表达在亚低温缺血组与常温缺血组间无明显差异外,其余各时间点亚低温缺血组Sur-vivin、BDNF表达均高于常温缺血组,差异有统计学意义(P<0.05)。结论亚低温干预可抑制梗死灶周围脑皮质神经细胞凋亡,促进存活素及脑源性神经营养因子的表达,发挥脑保护作用。     

亚低温对大鼠局灶性脑缺血再灌注后HIF-1α及凋亡相关蛋白变化的影响

目的观察病变侧亚低温对大鼠局灶性脑缺血再灌注后HIF-1α和Bcl-2蛋白变化的影响。方法用线栓法制作大鼠大脑中动脉闭塞(MCAO)局灶脑缺血再灌注模型,随机分为正常组、假手术组、常温缺血组和亚低温缺血组,于缺血2h再灌注3h、6h、12h、24h、72h、7d后处死,其中亚低温组于缺血后30min实施病灶侧脑亚低温并持续4h。处死前进行神经功能缺陷评分、HE染色、免疫组化检测HIF-1α和Bcl-2的表达。结果 (1)神经功能缺陷评分:亚低温缺血组大鼠各时间点均明显低于常温缺血组(P0.05);(2)HIF-1α的表达:再灌注3h表达显著增高,至24h左右达高峰,其后又随之下降,亚低温缺血组各时间点表达与常温缺血组无显著性差异(P0.05);(3)Bcl-2的表达:再灌注3h增多,随再灌注时间的延长,其表达逐渐增多(P0.05),6h达高峰,其后又随之下降,亚低温缺血组各时间点表达明显高于常温缺血组(P0.05)。结论 HIF-1α在脑缺血早期就发挥重要的保护作用。Bcl-2在脑缺血再灌注损伤过程中主要起抑制细胞凋亡的作用。亚低温能增加Bcl-2的表达;能明显减轻缺血所致的损伤,并能明显抑制细胞调亡;对大鼠缺血后神经功能的恢复有确切的疗效。     

大鼠局灶性脑缺血Bcl-2和Bax的表达与细胞凋亡

目的:研究大鼠局灶性脑缺血再灌注后凋亡相关基因Bcl-2和Bax在缺血皮层表达的变化及其与神经元凋亡的关系。方法:线栓法制作大鼠局灶性脑缺血再灌注模型,免疫组化法观察Bcl-2和Bax的表达变化,TUNEL法观察神经元凋亡的情况。结果:再灌注2h后皮层神经元Bcl-2表达开始明显上调,6h为高峰,之后开始下降。再灌注早期 Bax在皮层神经元的表达即明显增强,24～48h达高峰。Bcl-2／Bax的比率在再灌注开始时升高,6h达高峰,随后开始下降。TUNEL阳性细胞主要分布在缺血中心的边缘,再灌注48h之内,随时间的延长而不断增加。结论:Bcl-2／Bax的比率改变与缺血再灌注后的神经元存亡相关。     

人尿激肽原酶对大鼠局灶性脑缺血再灌注损伤的保护作用及对Caspase-3表达的影响

目的 观察人尿激肽原酶(HUK)对局灶性脑缺血再灌注损伤大鼠神经细胞凋亡及Caspase-3表达的影响. 方法 66只SD大鼠按随机数字表法分为假手术组(n=6)、缺血再灌注损伤组和HUK处理组,后两组又按不同观察时间点分为再灌注6h、12h、24 h、72 h、168 h共5个亚组(n=6).缺血再灌注损伤组和HUK处理组采用线栓法建立大鼠大脑中动脉局灶性脑缺血再灌注损伤模型,HUK处理组按浓度17.5×10-3PNAU/mL,1.0 mL/kg,于再灌注后3h尾静脉注射给药,1次/d.采用TUNEL法及免疫组化染色检测各组大鼠脑组织中凋亡细胞及Caspase-3阳性细胞的数量变化. 结果 脑缺血再灌注损伤后6h即有细胞凋亡,于24 h达到高峰,至168 h仍可见凋亡细胞.Caspase-3阳性细胞表达均于再灌注24 h达高峰,至168 h仍有较多表达.除168 h时间点外,其余各时间点HUK处理组大鼠神经细胞凋亡数量、Caspase-3阳性细胞数量均明显低于缺血再灌注损伤组,差异均有统计学意义(P＜0.05). 结论 HUK在大鼠局灶性脑缺血再灌注损伤早期(6～72h)时能抑制细胞凋亡,推测与其减少Caspase-3的表达有关.     

大鼠局灶性脑缺血再灌注后脑和肝、肾Bax、Bcl-2的蛋白表达

目的研究大鼠急性局灶性脑缺血再灌注后脑和肝、肾细胞凋亡和Bax、Bcl-2的蛋白表达变化,探讨急性局灶性脑缺血再灌注后对肝和肾脏的影响。方法参照Longa等的线栓法采用阻断大鼠大脑中动脉后再灌注（MCAO）,按随机原则将54只Wistar大鼠分为3个组：正常对照组（n=6）、假手术组（n=6）及缺血再灌注后2h、6h、12h、24h、48h、72h、5d 7个亚组,应用免疫组织化学SP染色技术检测脑和肝、肾Bax、Bcl-2的蛋白表达,并计数计算出平均阳性率（LI）,同时检测了肝和肾功能改变。结果（1）大鼠脑缺血再灌注后各时相点的肝、肾脏组织均有不同程度的病理损害；（2）Bax、Bcl-2在手术组的大鼠中呈明显的阳性表达,与正常对照组和假手术组之间比较有非常显著性差异（P＜0．01,P＜0．001）。结论大鼠急性局灶性脑缺血再灌注后肝、肾功能减退并出现组织细胞凋亡明显增加。     

GM1对高血压大鼠脑缺血再灌注后DNA损伤修复的影响

目的探讨GM1对局灶性脑缺血再灌注后神经元凋亡作用的机制。方法运用双肾双夹法建立肾血管性高血压大鼠模型,采用线栓法制备高血压大鼠短暂性局灶性脑缺血再灌注模型,免疫组化法检测再灌注过程中鼠脑DNA损伤修复蛋白XR—CC1、TUNEL法检测凋亡。结果与假手术组相比,脑缺血再灌注3h至24h在缺血区皮质XRCC1表达出现显著减低（P〈0.05）;再灌注24h缺血区皮质神经细胞发生凋亡,神经细胞XRCC1的表达强度与凋亡呈负相关。GM1治疗后缺血区皮质XRCC1的表达显著升高,凋亡显著减少（P〈0．05）。结论GM1通过提高肾血管性高血压大鼠局灶性脑缺血再灌注后神经细胞XRCC1的表达,发挥了抗神经细胞凋亡的作用。     

Changes of myosin and its ATPase in "neuronally" and "mechanically" contralateral muscles after cross-reinnervation in normal and capsaicin-treated rats

The extensor digitorum longus (EDL) muscle was cross-reinnervated by the soleus (SOL) nerve in normal and neonatally capsaicin-treated rats. After 5 months the muscles were investigated for their myofibrillar ATPase reaction and their myosin light and heavy chain composition. Besides the well known transformation of the cross-reinnervated EDL toward a slow muscle, muscular changes were also found in the contralateral leg. Although these changes were hardly detectable in the EDL muscle, a remarkable (70 to 100%) reduction of the fast type IIA fiber population was found in the SOL. The decrease of the number of IIA fibers (compared with time-matched controls) was paralleled by corresponding changes in the myosin light and heavy chain patterns. After the cross-reinnervation of a muscle, two kinds of contralaterality must be distinguished. In the experiments reported the cross-reinnervated EDL muscle remains "mechanically" contralateral to the EDL muscle of the other leg, while it becomes "neuronally" contralateral to the SOL muscle. Our results are interpreted as a symmetric "slowing down" of these "neuronally" contralateral muscles. Neonatal capsaicin treatment that decreased considerably the number of unmyelinated group IV afferent fibers did not influence the outcome of these experiments.     

实验性大鼠脑出血COX-2与MAP-2表达及作用

目的探讨实验性大鼠脑出血后脑组织COX-2和MAP-2的表达和两者之间的关系,及对脑组织神经元损伤的作用。方法用体重200³00 g健康的大鼠制作脑出血动物模型,将大鼠随机分为出血组和对照组;出血组分为自体血组和盐水对照组,自体血组按不同时间分为3 h、6 h、12 h、24 h、48 h、72 h、5 d、7 d、14 d、28 d、10个亚组,每组7只,盐水组为6 h组7只;正常对照组7只。用HE动态观察组织病理学改变,用免疫组织化学染色显示出血灶周围COX-2和MAP-2在脑组织内的表达。结果大鼠脑出血后脑组织COX-2于出血灶周围阳性细胞数于3 h增多,出血3 d达高峰,阳性细胞见于病变侧额顶部大脑皮质。脑出血组各时间点COX-2表达高于对照组,差异具有统计学意义(P<0.05);MAP-2表达于出血3 h开始减少,3 d下降到最低。脑出血3 h以后,紧邻血肿周围区MAP-2阳性细胞大量消失。3 d后虽有所增加但与对照组的差异仍有统计学意义(P<0.05)。结论COX-2主要在血肿周围的神经元表达,其高表达可能与血肿后继发性神经元损伤有关,脑出血后COX-2高表达促进了神经元的损伤,使MAP-2表达明显减少。     

胶质瘤中MMP-2和TIMP-2的表达及意义

目的探讨MMP-2和TIMP-2与胶质瘤侵袭性及恶性表型之间的关系及其意义。方法采用Elivision二步免疫组织化学法染色观察MMP-2和TIMP-2在46例不同恶性度胶质瘤及10例正常脑组织中的表达并用德国LeicaQ550cw图像分析系统测其灰度值作为表达强度的量化指标。结果在对照组、低度及高度恶性胶质瘤中,MMP-2的阳性表达率分别为10%、63.6%和95.8%;在对照组、低度及高度恶性胶质瘤中,TIMP-2的阳性表达率分别为10%、36.3%和37.5%。MMP-2在Ⅰ、Ⅱ级和Ⅲ、Ⅳ级胶质瘤中平均灰度值分别为173.27±13.26和98.63±18.20;TIMP-2在Ⅰ、Ⅱ级和Ⅲ、Ⅳ级胶质瘤中平均灰度值分别为210.44±12.95和205.65±9.75。结论MMP-2表达随胶质瘤恶性程度增加而增强,可作为胶质瘤恶性表型及侵袭性指标之一。TIMP-2表达在正常脑组织及不同级别胶质瘤中无明显差异。MMP-2/TIMP-2的比值与胶质瘤侵袭性密切相关。     

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.     

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.