人参总皂苷对创伤性脑损伤大鼠大脑皮质神经再生相关因子表达的影响

目的 创伤性脑损伤(TBI)后,采用人参总皂苷(GTS)治疗,测定大鼠皮质神经再生相关因子的变化,探讨GTS对神经损伤修复的作用.方法 采用改良Feeney法制备大鼠TBI模型,伤后6h,20 mg/kg GTS连续治疗7d,第14天观察皮质区神经再生相关因子的表达.Western - blot法检测NGF,、NCAM、Nogo -A,、Nogo -B,、TN - C190、TN - C220;免疫荧光法检测GFAP与GDNF.结果 TBI后损伤侧皮质神经再生促进因子(NGF、NCAM、GDNF)表达增强(1.232±0.007,1.086±0.024,49.0±3.00),神经再生抑制因子(Nogo -A、Nogo -B、TN - C190、TN - C220)表达也反应性增强(1.196±0.041,1.297 ±0.024,0.930 ±0.057,0.888 ±0.012);GTS治疗后NGF、NCAM、GDNF的表达进一步增强(1.276±0.003,1.184 ±0.022,68.4±2.79);Nogo -A、Nogo -B、TN -C190、TN - C220的表达(1.074±0.021,1.126 ±0.025,0.762±0.022,0.651±0.030)有所抑制.伤后皮质区GFAP表达增强(90.4±3.44),GTS治疗后有所下降(85.4±2.70).结论 TBI后,GTS通过调节神经再生相关因子的表达,除具有神经保护作用外,还可能促进脑皮质神经再生和组织修复,有利于神经功能恢复.     

脊髓缺血再灌注损伤模型的改进及对大鼠神经行为学的影响

目的建立并改进大鼠脊髓缺血再灌注损伤模型,为研究脊髓缺血病理机制和保护策略提供方法学基础。方法 56只成年SD雌性大鼠随机分为7组,每组8只。A组仅行手术操作,不阻断动脉;B、C、D组分别于结扎肾下腹主动脉60min、90min、120min后开放动脉实现脊髓再灌注;E、F、G组电凝肾上腹主动脉发出的椎动脉,再结扎肾下腹主动脉60min、90min、120min后再灌注。分别于术后12h、24h、48h对大鼠进行神经行为学评分,观察术后48h大鼠L2节段病理形态变化并计数前角运动神经元。结果各组行腹主动脉阻断术大鼠BBB评分于术后12h、24h、48h均显著低于A组(P<0.01),F和G组后肢功能障碍最为明显,BBB评分显著低于其它组(P<0.01);术后48h,F组和G组大量神经元坏死,Ⅷ、Ⅸ板层内正常神经元数明显少于其它各组(Ρ<0.01)。结论改良大鼠脊髓缺血再灌注损伤模型能够有效阻断腰段脊髓血液供应,改良模型脊髓常温下耐受缺血时限为90min。     

大鼠创伤性脑损伤VEGF表达的定量分析

在创伤性脑损伤（traumatic brain injury，TBI）的动物实验和临床研究中已发现血管内皮细胞生长因子（vascular endothelial growth factor，VEGF）的表达，认为TBI后VEGF的表达和上调与脑组织的自身保护有关。本研究应用激光共聚焦显微镜（laser scanning confocal microscopy，LSCM）对脑伤后动态VEGF表达进行荧光定量分析，以获得更为准确的VEGF表达时像，为应用VEGF治疗脑外伤提供一定的实验基础。     

内源性VEGF表达对缺血性脑损伤后成年大鼠海马齿状回神经发生影响的实验研究

2-EGFP-U6-shRNA(VEGF)立体定向给药大鼠缺血性脑损伤后24h和6d时缺血性脑损伤诱导的大鼠海马VEGF mRNA表达水平反应性升高可被抑制(P<0.05),海马内源性VEGF mRNA表达水平的降低可显著下调缺血性脑损伤后齿状回神经前体细胞增殖水平.结论 内源性VEGF基因表达可能是缺血性脑损伤后齿状回神经前体细胞增殖的一个重要启动信号.VEGF是耦联缺血性脑损伤和齿状回神经发生的关键分子.     

行为学训练对海马损伤梗死大鼠齿状回区BrdU和Nestin表达的影响

目的 探讨行为学训练对海马损伤梗死大鼠齿状回区神经干细胞增殖的影响。方法 采用光化学法制成单侧海马损伤梗死模型大鼠72只,随机分为训练组（n=36）和自由活动组（n=36）,每个组设1、7、14、21、28及35d 6个亚组。另设正常对照组36只,与模型组对应分为1、7、14、21、28及35d 6个亚组。训练组大鼠于造模1d后给予水迷宫训练,自由活动组大鼠自由活动,不予水迷宫训练。免疫荧光双标记法观察各不同时间点大鼠海马齿状回区溴脱氧尿嘧啶核苷（Bromodeoxyuridine,BrdU）与巢蛋白（Nestin）的双标记表达情况。结果 正常对照组大鼠海马齿状回区有少量BrdU/Nestin双标记阳性细胞,训练组及自由活动组大鼠在7、14、21及28d海马损伤梗死侧齿状回区BrdU/Nestin双标记阳性细胞数量均有显著增多（P <0.01）;训练组大鼠7、14、21、28d时海马损伤梗死侧齿状回区的BrdU/Nestin双标记阳性细胞数量显著高于自由活动组（P <0.01）;至35d时,训练组及自由活动组大鼠海马损伤梗死侧齿状回区BrdU/Nestin双标记阳性细胞数量与正常对照组无明显差异（P >0.05）。结论 行为学训练能显著增强海马损伤梗死大鼠齿状回区神经干细胞的增殖,促进神经功能恢复。     

三七总皂苷对脑梗死大鼠脑组织N-甲基-D天冬氨酸受体-1表达的影响

目的 探讨三七总皂苷(PNS)对脑梗死大鼠脑组织N-甲基-D天冬氨酸受体-1(NMDAR1)表达的影响.方法 24只Wistar大鼠应用线栓法制作脑梗死模型,并随机分为PNS组与对照组,每组再随机分术前及术后干预亚组,每亚组大鼠雌雄各半.不同亚组大鼠分别于术前或术后给予PNS 100 mg/kg或等量的生理盐水腹腔注射每日1次共3d;制模后第4d观察各组缺血区脑组织形态学变化,免疫组化染色观察脑组织NMDAR1蛋白的表达.结果 与对照组比较,PNS组缺血区脑组织病理改变程度明显减轻,脑组织NMDAR1阳性细胞明显减少(P＜0.01);术后干预亚组较术前干预亚组明显减少(P＜0.01).结论 PNS可明显降低脑组织NMDAR1的表达,减轻脑梗死大鼠脑组织病理改变程度,术后干预的神经保护作用更明显.     

骨髓基质干细胞移植对脑损伤大鼠神经行为学和血管再生的影响

目的探索移植骨髓基质干细胞(BMSCs)对局灶性脑损伤大鼠的神经功能修复的作用及血管再生的影响,探讨BMSCs移植促进大鼠脑损伤修复的机制。方法 30只大鼠制备大鼠局灶性脑损伤动物模型,随机分为假手术组、脑损伤组和BMSCs移植组,每组10只大鼠。取供体鼠BMSCs,体外扩增,DAPI荧光标记。在脑立体定向仪引导下将BMSCs移植到脑损伤大鼠局部损伤灶边缘,于3d、7d及14d通过观察大鼠神经行为能力的变化,评价移植细胞后大鼠神经功能的修复情况;14d后取脑组织荧光显微镜观察移植细胞存活的情况,采用免疫组化法检测脑组织微血管密度(MVD)来评估血管再生情况、血管内皮生长因子(VEGF)、血管内皮生长因子受体(Flt-1、Flk-1)的蛋白表达情况。结果脑损伤组和BMSCs移植组于移植后3d时神经行为学评分差异无统计学意义(P>0.05),而在移植后7d、14d,BMSCs移植组与脑损伤组在神经行为学评分指标上差异有统计学意义(P<0.05)。BMSCs移植组与脑损伤组比较,脑组织微血管密度明显增加,VEGF和Flt-1、Flk-1表达明显增加。结论骨髓基质干细胞移植后可促进脑损伤大鼠神经功能的恢复,其机制可能与其增加VEGF和Flt-1、Flk-1表达促进血管再生有关。     

远志总皂苷对AD模型大鼠海马Ng及pCaMKⅡα表达的影响

目的观察远志总皂苷(TEN)对阿尔茨海默病(AD)模型大鼠海马CA1区神经颗粒素(Ng)以及磷酸化的钙/钙调蛋白依赖性蛋白激酶Ⅱα亚基(pCaMKⅡα)表达的影响,探讨TEN防治AD的作用机制。方法将60只雄性Wistar大鼠随机分为对照组,模型组,TEN低剂量治疗组(12.5mg/ml)和TEN高剂量治疗组(37.5 mg/ml),每组15只,模型组予以腹腔注射D-半乳糖(D-gal)致衰并联合鹅膏覃氨酸(IBO)定向Meynert基底核损毁法建立AD大鼠模型,TEN低、高剂量治疗组则在造模的同时TEN灌胃治疗8w,对照组则用等体积的生理盐水代替D-gal和IBO。采用免疫组化方法来检测大鼠海马CA1区Ng及pCaMKⅡα的表达。结果模型组大鼠海马CA1区Ng及pCaMKⅡα平均吸光度值比对照组显著降低(P<0.01);TEN治疗组两组平均吸光度值均较模型组显著增高(P<0.01);且TEN高剂量治疗组(37.5 mg/ml)的平均吸光度值比TEN低剂量治疗组(12.5mg/ml)显著增高(P<0.01)。结论 TEN可显著升高AD模型大鼠海马CA1区Ng及pCaMKⅡα的表达,且具有剂量依赖性。     

远志总皂苷对阿尔茨海默病模型大鼠海马脑源性神经营养因子及酪氨酸蛋白激酶B表达的影响

目的观察远志总皂苷对阿尔茨海默病模型大鼠海马CA1区脑源性神经营养因子(BDNF)及其特异性受体酪氨酸蛋白激酶B(TrkB)表达的影响,探讨远志总皂苷对阿尔茨海默病的干预作用机制。方法雄性Wistar大鼠被随机分为生理盐水组(正常对照组)、阿尔茨海默病模型组(模型组),以及远志总皂苷低剂量(12.50 mg/ml)和高剂量(37.50 mg/ml)组;采用D-半乳糖致衰老联合鹅膏覃氨酸损毁基底前脑Meynert核法建立阿尔茨海默病大鼠模型,免疫组织化学染色检测大鼠海马CA1区BDNF及其受体TrkB表达水平。结果 BDNF和TrkB阳性物质呈棕黄色,主要表达于海马CA1区神经元胞膜。模型组大鼠海马CA1区BDNF及其受体TrkB表达水平为0.30±0.02和0.21±0.07,低于正常对照组的0.47±0.02和0.46±0.05(均P=0.000);与模型组相比,远志总皂苷低剂量组(0.35±0.05,0.32±0.07)和高剂量组(0.43±0.05,0.37±0.03)大鼠海马CA1区BDNF及其受体TrkB表达水平均显著升高(均P=0.000),但以高剂量组升高更为显著(均P=0.000)。结论远志总皂苷可以显著升高阿尔茨海默病模型大鼠海马CA1区BDNF及其受体TrkB表达水平,且具有剂量依赖性,这可能是其改善认知功能的机制之一。     

三七总皂苷对脑缺血再灌注损伤保护作用的实验研究

探讨三七总皂苷在大鼠局灶性脑缺血 /再灌注损伤中的保护作用及其可能机制。材料与方法选用 6 6只健康 3月龄雌性Ｗｉｓｔａｒ大鼠 ,体重 2 0 0～ 30 0ｇ ,随机分为 :中药组、对照组和假手术组 ,每组2 2只。三七总皂苷注射液为纯中药制剂 (批号 :ＺＺ 5 5 5 9 陕卫药准字 [1995 ]第 0 0 0 80 6号 ,商品名 ;脑明注射液 )。将上述大鼠切除双侧卵巢制成去势大鼠模型 ,2周后采用稍加改良的Ｎａｇａｓａｗａ[1] 法将上述大鼠制成ＭＣＡＯ模型。于ＭＣＡＯ后 30ｍｉｎ给药。均给于三七总皂苷注射液 (2ｍＬｉｐ)相当于生药 3ｍｇ·ｋｇ- 1,随之每隔…     

人参皂苷F组对急性脑缺血大鼠细胞凋亡及VEGF表达的影响

目的研究F组人参皂苷对急性脑缺血大鼠脑细胞凋亡及VEGF表达的影响。方法参照ZeaLonga线栓法制作右侧大脑中动脉栓塞模型。选用健康雄性Wistar大鼠70只,随机分为5组:假手术组、盐水对照组、小剂量给药组、中剂量给药组、大剂量给药组。给药组分别于术前30m in及术后30m in、3h给予不同剂量的F组人参皂苷腹腔内注射。应用TTC染色及图像分析系统测定脑缺血24h后的梗死体积、TUNEL染色观察各组间细胞凋亡的差异及免疫组化染色检测VEGF表达的变化。结果与盐水对照组相比,药物干预组局部脑缺血后在相同时间内梗死灶体积减小(P<0.05);神经细胞凋亡减少(P<0.05),且随剂量的增加凋亡细胞减少更加明显(P<0.01);VEGF表达明显增加(P<0.01),且在实验剂量范围内其表达随药物剂量的增加而增多(P<0.01)。结论F组人参皂苷对脑缺血损伤具有保护作用,其机制为减少细胞凋亡及增加VEGF表达。     

人参皂苷对癫痫大鼠行为学和突触蛋白的影响

目的探讨人参皂苷Rb1对癫痫大鼠学习记忆及海马kalirin-7和突触后致密物95(PSD-95)表达的影响。方法 40只SD大鼠随机分为4组:对照组、模型组、Rb1低、高剂量组。模型制备成功后,采用Morris水迷宫检测其行为学,电镜法观察海马CA1区突触超微结构,Western blot法检测海马kalirin-7和PSD-95的表达。结果模型组大鼠的末次逃避潜伏期、穿台次数、海马CA1区PSD厚度、kalirin-7和PSD-95表达[分别为(11.2±1.6)s、(4.9±1.3)次、(25.9±2.4)nm、(0.32±0.03)、(0.95±0.08)];与对照组[分别为(4.5±0.8)s、(10.9±2.1)次、(34.1±3.7)nm、(0.86±0.07)、(1.94±0.13)],比较均具有显著性差异(P<0.05)。而人参皂苷Rb1干预组剂量依赖性地逆转了上述的异常变化(P<0.05)。结论人参皂苷Rb1可能通过上调海马kalirin-7和PSD-95蛋白的表达来改善癫痫大鼠的认知功能障碍。     

重复经颅磁刺激对抑郁模型大鼠行为学及海马区糖皮质激素受体表达的影响

目的观察重复经颅磁刺激(repetitive transcranial magnetic stimulation,r TMS)对慢性应激抑郁模型大鼠的抗抑郁作用及对海马区糖皮质激素受体(glucocorticoid receptor,GR)表达的影响,探讨r TMS抗抑郁作用的可能机制。方法 75只健康成年雄性大鼠随机分为造模组(60只)和空白对照组(15只),造模组采用孤养联合慢性温和不可预见应激(chronic unpredictability stimulus,CUMS)方法制备抑郁大鼠模型,为期3周,筛选造模成功的大鼠45只随机分为r TMS组、伪r TMS组和抑郁对照组,每组15只,r TMS组和伪r TMS组分别接受10 Hz的r TMS刺激和伪刺激干预3周,抑郁对照组和空白对照组不给予干预。分别于造模前、造模后、r TMS干预后进行体重测量、蔗糖水消耗实验和强迫游泳实验评估,r TMS干预后检测大鼠海马区GR蛋白和海马GR m RNA表达水平。结果造模后,r TMS组、伪r TMS组和抑郁对照组大鼠蔗糖水消耗量较空白对照组下降,强迫游泳不动时间增加(P0.01)。r TMS干预后,r TMS组体重增长率、蔗糖水消耗量与伪r TMS组和抑郁对照组相比均较高(P0.01),强迫游泳不动时间较短(P0.01)。伪r TMS组及抑郁对照组海马区GR蛋白及其m RNA表达水平与r TMS组和空白对照组相比均较低(P0.05)。结论 r TMS能够改善CUMS抑郁模型大鼠的抑郁样行为,可能与上调海马区GR表达有关。     

更正:远志总皂苷对阿尔茨海默病模型大鼠海马脑源性神经营养因子及酪氨酸蛋白激酶B表达的影响

<正>由于第一作者陈伟荣个人疏忽,特申请将我刊2014年第14卷第5期远志总皂苷对阿尔茨海默病模型大鼠海马脑源性神经营养因子及酪氨酸蛋白激酶B表达的影响[1]一文脚注作者单位:030032太原,山西医学科学院山西大医院神经内科改为作者单位:030001太原,山西医科大学研究生院2011级(陈伟荣,燕毅男,崔红丽);030032太原,山西医学科学院山西大医院神经内科(李新毅),英文作者名CHEN Wei-rong,YAN Yi-nan,CUI Hong-li,LI Xin-yi改为CHEN Wei-rong1,YAN Yi-nan1,CUI Hong-li1,LI Xin-yi2,英文单位Department of Neurology,Shanxi Da Yi Hospital,Shanxi Academy of Medical Sciences,     

液压脑损伤大鼠行为学和脑电图的研究

目的 通过液压脑损伤大鼠行为学和脑电图的研究以探讨其在外伤后癫痫中的研究价值.方法 建立液压脑损伤动物模型并进行为期3个月大鼠行为学和脑电图的观察、记录.结果 液压脑损伤后50只大鼠死亡19只,存活的31只中有11只出现癫痫.癫痫的发作形式主要表现为面肌痉挛、点头样运动,其次为四肢抽搐、翻转跳起等.液压脑损伤后第2个月为癫痫发生的高峰期.癫痫发作时同期脑电图可见癫痫样放电.液压脑损伤后部分非癫痫大鼠脑电图表现为1～5导联波幅增高、频率增快.结论 液压脑损伤后癫痫动物模型与临床外伤后癫痫相似,与其他外伤后癫痫动物模型相比,更具有研究价值.     

液压脑损伤大鼠行为学和脑电图的研究

Objective To investigate the electroencephalogram and ethology in the rat with fluid percussion brain injury and approach its research value in the post traumatic epilepsy. Methods The change of ethology and electroencephalogram of rat in the three months after fluid percussion brain injury were observed and recorded. Results Among the survival 31 rats, there were 11 rats that appeared epilepsy. Epileptic seizure manifestation principally appeared as facial spasm, nod motion, and next limbs convulsion and turnover upspring, et al. The highest epileptic incidence rate appeared in 2 months after lateral fluid percussion brain injury. There were obvious epileptic discharges on the electroencephalogram of epileptic rats and higher wave amplitude and quicker frequency on the lead of 1～5 on the electroencephalogram of some no epileptic rats. Conclusions Post traumatic epilepsy after lateral fluid percussion brain injury in rat is similar with clinical post traumatic epilepsy. It has more research value than the other pest traumatic epileptic animal model.     

液压脑损伤大鼠行为学和脑电图的研究

Objective To investigate the electroencephalogram and ethology in the rat with fluid percussion brain injury and approach its research value in the post traumatic epilepsy. Methods The change of ethology and electroencephalogram of rat in the three months after fluid percussion brain injury were observed and recorded. Results Among the survival 31 rats, there were 11 rats that appeared epilepsy. Epileptic seizure manifestation principally appeared as facial spasm, nod motion, and next limbs convulsion and turnover upspring, et al. The highest epileptic incidence rate appeared in 2 months after lateral fluid percussion brain injury. There were obvious epileptic discharges on the electroencephalogram of epileptic rats and higher wave amplitude and quicker frequency on the lead of 1～5 on the electroencephalogram of some no epileptic rats. Conclusions Post traumatic epilepsy after lateral fluid percussion brain injury in rat is similar with clinical post traumatic epilepsy. It has more research value than the other pest traumatic epileptic animal model.     

液压脑损伤大鼠行为学和脑电图的研究

Objective To investigate the electroencephalogram and ethology in the rat with fluid percussion brain injury and approach its research value in the post traumatic epilepsy. Methods The change of ethology and electroencephalogram of rat in the three months after fluid percussion brain injury were observed and recorded. Results Among the survival 31 rats, there were 11 rats that appeared epilepsy. Epileptic seizure manifestation principally appeared as facial spasm, nod motion, and next limbs convulsion and turnover upspring, et al. The highest epileptic incidence rate appeared in 2 months after lateral fluid percussion brain injury. There were obvious epileptic discharges on the electroencephalogram of epileptic rats and higher wave amplitude and quicker frequency on the lead of 1～5 on the electroencephalogram of some no epileptic rats. Conclusions Post traumatic epilepsy after lateral fluid percussion brain injury in rat is similar with clinical post traumatic epilepsy. It has more research value than the other pest traumatic epileptic animal model.     

液压脑损伤大鼠行为学和脑电图的研究

Objective To investigate the electroencephalogram and ethology in the rat with fluid percussion brain injury and approach its research value in the post traumatic epilepsy. Methods The change of ethology and electroencephalogram of rat in the three months after fluid percussion brain injury were observed and recorded. Results Among the survival 31 rats, there were 11 rats that appeared epilepsy. Epileptic seizure manifestation principally appeared as facial spasm, nod motion, and next limbs convulsion and turnover upspring, et al. The highest epileptic incidence rate appeared in 2 months after lateral fluid percussion brain injury. There were obvious epileptic discharges on the electroencephalogram of epileptic rats and higher wave amplitude and quicker frequency on the lead of 1～5 on the electroencephalogram of some no epileptic rats. Conclusions Post traumatic epilepsy after lateral fluid percussion brain injury in rat is similar with clinical post traumatic epilepsy. It has more research value than the other pest traumatic epileptic animal model.     

液压脑损伤大鼠行为学和脑电图的研究

Objective To investigate the electroencephalogram and ethology in the rat with fluid percussion brain injury and approach its research value in the post traumatic epilepsy. Methods The change of ethology and electroencephalogram of rat in the three months after fluid percussion brain injury were observed and recorded. Results Among the survival 31 rats, there were 11 rats that appeared epilepsy. Epileptic seizure manifestation principally appeared as facial spasm, nod motion, and next limbs convulsion and turnover upspring, et al. The highest epileptic incidence rate appeared in 2 months after lateral fluid percussion brain injury. There were obvious epileptic discharges on the electroencephalogram of epileptic rats and higher wave amplitude and quicker frequency on the lead of 1～5 on the electroencephalogram of some no epileptic rats. Conclusions Post traumatic epilepsy after lateral fluid percussion brain injury in rat is similar with clinical post traumatic epilepsy. It has more research value than the other pest traumatic epileptic animal model.