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1.
细胞周期调控对局灶性缺血性脑损伤后的保护作用   总被引:1,自引:1,他引:0  
目的通过抑制细胞周期素依赖激酶(Cyclindependentkinases,CDKS)来对神经元凋亡进行干预,以探讨细胞周期调控与细胞凋亡的关系。方法建立光化学法诱导大鼠局灶性脑缺血模型,并随机分为脑缺血组(对照组和干预组)和假手术组,采用HE染色显示梗死灶,并测定其面积占脑片面积百分率的平均值;通过TUNEL方法检测神经元凋亡;免疫印迹(Westernblot)观察损伤侧皮层周期素蛋白A(CyclinA)和周期素蛋白B1(CyclinB1)的表达。结果缺血后24h对照组梗死灶面积占脑片面积百分率的平均值明显大于干预组(P<0.05),缺血后梗死灶周围可见大量TUNEL阳性染色细胞,且对照组数量明显多于干预组(P<0.05),二者均多于假手术组(P<0.05);缺血后24h干预组大鼠NeuN TUNAL双标阳性表达率明显弱于对照组大鼠(P<0.05);Westernblot显示对照组CyclinA和CyclinB1的表达明显高于干预组(P<0.05)。结论细胞周期抑制剂可部分抑制缺血边缘区神经元的凋亡及减小脑梗死面积,这提示细胞周期调控可能参与了神经细胞的凋亡过程。  相似文献   

2.
目的观察细胞周期调控对局灶性脑缺血边缘区胶质细胞增殖及神经元凋亡的影响。方法选用细胞周期蛋白D1(cyclin D1)基因敲除小鼠,建立光化学诱导小鼠局灶性脑缺血模型,随机将实验动物分为脑缺血组和假手术组,采用尼氏染色显示脑梗死灶并计算梗死灶面积;应用免疫荧光化学方法检测胶质纤维酸性蛋白(GFAP)的表达;并通过TUNEL方法检测神经元凋亡。结果缺血后3、7、28d cyclin D1基因敲除纯合子小鼠梗死灶面积占脑片总面积比值(1·00±0·28,1·00±0·16,1·10±0·16)明显小于杂合子(3·60±0·47,3·80±0·28,4·20±0·24)及野生型小鼠(3·60±0·51,3·90±0·21,4·30±0·47,均P<0·05);缺血后各时间组缺血边缘区GFAP表达明显增强,但缺血后7、28d纯合子小鼠缺血边缘区GFAP的表达明显弱于杂合子及野生型小鼠(缺血后7、28d纯合子小鼠缺血边缘区GFAP的吸光度值依次为0·612±0·069,0·622±0·146,杂合子为0·838±0·089,0·998±0·172,野生型为0·863±0·076,1·054±0·124,均P<0·05);缺血后3d于缺血边缘区可见大量TUNEL阳性染色细胞,而且杂合子、野生型小鼠缺血区细胞凋亡数目明显多于纯合子小鼠(缺血3d后纯合子、杂合子、野生型TUNEL阳性率依次为7·00±3·01,23·30±7·59,25·50±8·77,P<0·05);纯合子小鼠抗神经元特异性核蛋白(NeuN) TUNEL双标阳性的结果明显弱于杂合子和野生型小鼠(P<0·05)。结论通过cyclin D1基因敲除,可部分抑制缺血边缘区胶质细胞增殖,同时减少神经元凋亡和脑梗死面积。该结果提示调控细胞周期可能是脑缺血新的治疗方向。  相似文献   

3.
ERK对缺血缺氧性脑损伤后神经元凋亡的影响   总被引:1,自引:0,他引:1  
目的研究在缺血缺氧性脑损伤后细胞外信号调节激酶(ERKs)对神经元凋亡的影响。方法建立光化学法诱导大鼠局灶性脑缺血模型,随机分为脑缺血组(缺血组和干预组)和假手术组,干预组于缺血前30min尾静脉注入U0126溶液,缺血组尾静脉注入相同体积不含U0126的DMSO稀释溶液;2,3,5-氯化(或溴化)三苯四氮唑(TTC)染色显示梗死灶;应用免疫组织荧光化学法检测梗死灶周围神经元核心抗原(NeuN)的表达及通过TUNEL方法检测神经元凋亡,并做NeuN与TUNEL的双标;用免疫印迹(Westernblot)方法观察损伤侧皮层NeuN、细胞周期蛋白D1(CyclinD1)和细胞周期蛋白E(CyclinE)蛋白的表达。结果缺血组的梗死体积明显大于干预组,在假手术组未见梗死灶;缺血组大鼠NeuN阳性细胞数和NeuN蛋白表达明显少于假手术组,TUNEL阳性细胞数和CyclinD1和CyclinE蛋白表达明显高于假手术组(P<0.05)。干预组NeuN阳性细胞数和NeuN蛋白表达亦少于假手术组,但多于缺血组,TUNEL阳性细胞数和CyclinD1及CyclinE蛋白表达亦多于假手术组,但少于缺血组(P<0.05)。结论ERK可通过对细胞周期的调控而对神经元凋亡产生影响,抑制脑缺血引起的pERK1/2磷酸化可部分抑制神经元凋亡,减少缺血梗死灶,对缺血性脑损伤起一定的保护作用。  相似文献   

4.
目的 观察病变侧缺血至再灌期亚低温 (32~ 33℃ )对局灶脑缺血再灌注后梗死体积、星形胶质细胞胶质纤维酸性蛋白 (GFAP)表达的影响。方法 采用改良线栓法建立大鼠大脑中动脉缺血再灌注模型 ,缺血 30min后应用反馈控温半导体制冷块对大鼠病变侧给予亚低温治疗 ,并持续至再灌期。采用免疫组织化学方法检测GFAP表达 ,TTC染色测梗死体积。结果 同常温组相比梗死体积明显减少 (P <0 .0 5 ) ,缺血常温组GFAP阳性细胞数量增多 ,突体粗大 ,胞体肿胀 ;亚低温组GFAP表达数量明显减少。结论 病变侧亚低温能明显抑制脑缺血后星形胶质细胞反应性增生和肥大。缺血至再灌期亚低温明显减轻脑组织损伤。  相似文献   

5.
目的探讨细胞周期调控对脑神经细胞凋亡的影响。方法采用光化学方法制作大鼠局灶性缺血模型,术后立即腹腔注射细胞周期抑制剂Olomoucine进行干预。HE染色来测定皮层梗死灶的体积;应用免疫组织化学法观察缺血后第3天假手术组、缺血对照组和干预组大鼠损伤侧皮层病灶周围凋亡神经细胞的表达;聚丙烯酰胺凝胶电泳(Western blot)和半定量逆转录-聚合酶链式反应(RT-PCR)观察Caspase-3蛋白及mRNA的表达。结果 HE染色显示对照组梗死灶明显大于干预组;免疫组织化学可见病灶周围凋亡神经细胞的阳性表达,干预组较假手术组显著增高,但明显低于对照组(P<0.05);Western blot和RT-PcR显示Caspase-3蛋白和mRNA的表达,干预组较假手术组增高(P<0.05),而较对照组明显降低(P<0.05)。结论脑缺血损伤后细胞周期调控参与了迟发性神经元的死亡过程。  相似文献   

6.
目的探讨肾上腺髓质素(adrenomedullin, ADM)对局灶性脑缺血再灌注大鼠神经元凋亡、梗死体积及早期生长反应基因Egr-1 mRNA表达的影响,进一步研究ADM在局灶性缺血再灌注脑损伤中的作用。方法采用线栓法制成大鼠大脑中动脉缺血再灌注(MCAO)模型,阻断血流2 小时后进行再灌注。TTC染色法测定梗死体积,TUNEL法检测神经元凋亡,原位杂交法检测Egr-1 mRNA阳性细胞表达。结果大鼠局灶性脑缺血再灌注后脑梗死体积为269 ± 20 mm3,股静脉、颈动脉、侧脑室注射ADM 后,梗死体积分别缩小为239 ± 17mm3(减少11.2%),214 ± 14 mm3 (减少20.4%),209 ± 13 mm3 (减少22.3%)。颈动脉注射ADM和侧脑室注射ADM在减少脑梗死体积方面明显优于股静脉注射ADM(P < 0.05)。缺血再灌注组大鼠缺血侧大脑皮质、海马CA1区TUNEL染色阳性细胞明显多于假手术组(P < 0.01)。给予ADM后缺血侧大脑皮质、海马CA1区TUNEL染色阳性细胞显著少于缺血再灌注组,以颈动脉给予ADM组和侧脑室给予ADM组更明显(P < 0.01)。假手术组大鼠大脑皮质有少量Egr-1mRNA阳性细胞表达,缺血再灌注后缺血侧大脑皮质、海马Egr-1mRNA阳性细胞表达多于假手术组(P < 0.01),应用ADM后三组大鼠大脑皮质、海马Egr-1 mRNA阳性细胞的表达明显高于缺血再灌注组(P < 0.01),但以颈动脉给予ADM组和侧脑室给予ADM组Egr-1 mRNA阳性细胞表达增高最明显(P < 0.01)。结论股静脉、侧脑室和颈动脉给予外源性ADM能减少神经元凋亡,减少梗死体积,激活Egr-1 mRNA的表达。  相似文献   

7.
目的 从胶质细胞源性神经营养因子(GDNF)对大鼠局灶脑缺血梗死灶、半胱氨酸蛋白酶(Caspase-3)表达、细胞凋亡等方面的影响,研究其对大鼠局灶脑缺血的作用及其机制。方法 健康雄性Wistar大鼠120只,随机分为GDNF组和生理盐水组,每组又分为假手术组、缺血oh、3h、6h、24h组,采用大脑中动脉线栓模型,于栓塞同时大鼠脑室内分别给予GDNF和生理盐水5μL。检测脑梗死体积百分比、Caspase-3的表达、细胞凋亡等改变。结果 GDNF组脑梗死体积比明显小于生理盐水组;神经元损伤明显轻于生理盐水组,特别是海马区神经元在GDNF组无明显损伤;GDNF组(Caspase-3表达和TUNEL染色阳性细胞数明显少于生理盐水组。结论 GDNF对大鼠局灶脑缺血有保护作用,抑制Caspase-3的表达和细胞凋亡是其保护机制之一。  相似文献   

8.
目的观察大鼠大脑缺血再灌注后海马CA1区胶质纤维酸性蛋白(GFAP)的表达与迟发性神经元死亡的关系。方法采用大鼠大脑中动脉阻塞再灌注模型(MCAO),将大鼠随机分为MCAO后3d、7d、30d组及假手术组,应用免疫荧光与TUNEL染色法分别观察脑缺血再灌注后不同时间点缺血侧海马CA1区GFAP表达情况和迟发性神经元死亡(DND)的变化。结果(1)3d组海马DND阳性(DND 组)的MCAO大鼠、海马DND阴性(DND-组)的MCAO大鼠与假手术组大鼠比较,缺血侧海马CA1区GFAP染色的平均光密度无显著性差异(P>0.05),但GFAP阳性细胞的形态发生变化;(2)7d组大鼠缺血侧海马CA1区GFAP阳性细胞大量活化增殖,表现为胞体变大,突起增多;DND( )、DND(-)组海马CA1区GFAP染色的平均光密度较假手术组增高(P<0.01),且DND(-)组的GFAP平均光密度较DND( )组明显增高(P<0.01);(3)30d组大鼠缺血侧海马CA1区GFAP表达呈瘢痕样改变,DND( )、DND(-)组与假手术组比较其GFAP染色的平均光密度明显增高(P<0.05),且DND( )组的GFAP平均光密度较DND(-)组明显增高(P<0.05)。结论大鼠MCAO后星形胶质细胞反应性变化的差异可能与海马CA1区迟发性神经元死亡的发生有关。  相似文献   

9.
目的 研究成年大鼠持续性局灶脑缺血后小胶质细胞的变化及其与缺血后凋亡的关系。方法 采用单侧大脑中动脉近端民凝术建立成年大鼠持续性局灶脑缺血模型。在手术后3h、6h、12h、24h、48h、72h和120h取材,分别用IsolectinB4凝集素标记小胶质细胞和原位末端TUNEL法标记凋亡细胞。结果 缺血后凝集素阳性小胶质细胞和TUNEL阳性小胶质细胞都分布在梗死灶周边区。缺血12h在梗死灶的边缘密集分布凝集素标记阳性细胞,24-72h凝集素阳性小胶质细胞数量增加(P<0.05),120h阳性细胞数量减少(P<0.01)。脑缺血48h、72h、120h在梗死灶边缘区域分布TUNEL阳性凋亡细胞,TUNEL阳性细胞以神经细胞为主。结论 持续性局灶脑缺血后活化小胶质细胞主要分布在梗死灶周边区,可能对缺血后神经元凋亡产生作用。  相似文献   

10.
目的 探讨大鼠局灶性脑缺血再灌注后少突胶质细胞的病理学改变.方法 应用改良插线法制作大鼠脑缺血再灌注模型.应用免疫组化方法检测大鼠tau-1蛋白的表达水平,以大鼠白质缺血区tau-1蛋白表达阳性的细胞体积定量少突胶质细胞的损伤,并分析其与神经元核周体损伤的关系.结果 模型组大鼠缺血侧皮质和尾壳核可见大量缺血坏死的神经元及tau-1蛋白表达,而正常对照组大鼠未出现缺血坏死的神经元及tau-1蛋白表达增加;模型组大鼠少突胶质细胞损伤体积和神经元核周体损伤体积呈正相关(r=0.895,P<0.01).结论 少突胶质细胞易受局灶性缺血性损伤,通过检测tau-1蛋白的表达可定量显示少突胶质细胞的损伤程度,为白质损伤的研究提供评估标准.  相似文献   

11.
Decades of intervention research have produced a rich body of evidence on the effects of psychotherapies and pharmacotherapies with children and adolescents. Here we summarize and critique that evidence. We review findings bearing on the efficacy of psychosocial treatments and medications under controlled experimental conditions. We also report evidence, where available, on the effectiveness of both classes of treatment with clinically referred youth treated in real-world clinical contexts. In general, the large body of evidence on efficacy contrasts sharply with the small base of evidence on effectiveness. Addressing this gap through an enriched research agenda could contribute importantly to linking scientific inquiry and clinical practice—to the benefit of both ventures. This is one element of a multifaceted agenda for future research and for synthesis of research, which will require the interplay of multiple disciplines related to child and adolescent mental health.  相似文献   

12.
F.S. Labella 《Brain research》1981,219(1):166-171
Specific binding of [3H]naloxone to rat brain tissue in vitro was inhibited by the excitant organochlorinated insecticides (OCI), by ether (E) and octanol (OCT), and by the convulsant indoklon (IND) and its anesthetic isomer, isoindoklon (ISO). In the presence of 100 mM NaCl the inhibition of naloxone binding by E, OCT and ISO was greatly potentiated, whereas that by OCI and IND was attenuated. KCl (100 mM) was equally effective as NaCl on the action of anesthetics, but the effect of the excitant drugs was, in contrast to NaCl, unaffected by KCl. Specific binding of [3H]ouabain in the absence of Na, was depressed by anesthetics and enhanced by neuroexcitants. In the presence of NaCl, which by itself inhibits ouabain binding to brain, both anesthetics and excitants enhanced ouabain binding. DDE, a non-insecticidal analog of DDT, and the dimethyl derivative of the OCI, lindane, were inactive in the receptor assays. These observations point to a unique isolated system which responds consistently to anesthetic agents as a class and, in a different way, to neuroexcitant compounds.  相似文献   

13.
We studied how subjects with mild cognitive impairment (MCI), early Alzheimer's disease (AD) and age-matched controls learned and maintained the names of unfamiliar objects that were trained with or without semantic support (object definitions). Naming performance, phonological cueing, incidental learning of the definitions and recognition of the objects were tested during follow-up. We found that word learning was significantly impaired in MCI and AD patients, whereas forgetting patterns were similar across groups. Semantic support showed a beneficial effect on object name retrieval in the MCI group 8 weeks after training, suggesting that the MCI patients’ preserved semantic memory can compensate for impaired episodic memory. The MCI group performed equally well as the controls in the tasks measuring incidental learning and recognition memory, whereas the AD group showed impairment in this respect. Both the MCI and the AD group benefited less from phonological cueing than the controls. Our findings indicate that word learning is compromised in both MCI and AD, whereas long-term retention of newly learned words is not affected to the same extent. Incidental learning and recognition memory seem to be well preserved in MCI.  相似文献   

14.
在神经系统 ,Necdin只在成熟神经元的细胞核中表达 ,可能与成熟神经元分裂静止状态的保持有关。近年的研究表明 ,Necdin是一种生长抑制蛋白 ,能与多种因子如SV4 0大T抗原 ,腺病毒E1A ,转录因子E2F1以及肿瘤抑制蛋白p5 3等结合 ,在功能上类似于成视网膜瘤蛋白Rb。necdin基因缺陷时 ,会引起脑内 ,特别是下丘脑神经元分化障碍。人类necdin基因位于PWS综合征的基因缺失区 ,可能与PWS的一些症状有关。本文从Necdin蛋白的基本概况 ,生物功能以及Necdin与疾病三个方面进行了综述  相似文献   

15.
Satellite cells and myonuclei in young and elderly women and men   总被引:12,自引:0,他引:12  
The overall aim of this study was to assess the effects of aging on the satellite cell population. Muscle biopsies were taken from the tibialis anterior muscle of healthy, moderately active young (age range, 20-32 years; n = 31) and elderly (age range, 70-83 years; n = 27) women and men with comparable physical activity pattern. Satellite cells and myonuclei were visualized using a monoclonal antibody against neural cell adhesion molecule and counterstained with Mayer's hematoxylin. An average of 211 (range, 192-241) muscle fibers were examined for each individual. Compared with the young women and men, the elderly subjects had a significantly lower (P < 0.011) number of satellite cells per muscle fiber but a significantly higher (P < 0.004) number of myonuclei per muscle fiber. The number of satellite cells relative to the total number of nuclei [satellite cells/(myonuclei + satellite cells)] was significantly lower in the elderly than in the young women and men. These results imply that a reduction in the satellite cell population occurs as a result of increasing age in healthy men and women.  相似文献   

16.
在神经系统,Necdin只在成熟神经元的细胞核中表达,可能与成熟神经元分裂静止状态的保持有关.近年的研究表明,Necdin是一种生长抑制蛋白,能与多种因子如SV40大T抗原,腺病毒E1A,转录因子E2F1以及肿瘤抑制蛋白p53等结合,在功能上类似于成视网膜瘤蛋白Rb.necdin基因缺陷时,会引起脑内,特别是下丘脑神经元分化障碍.人类necdin基因位于PWS综合征的基因缺失区,可能与PWS的一些症状有关.本文从Necdin蛋白的基本概况,生物功能以及Necdin与疾病三个方面进行了综述.  相似文献   

17.
The study of the presentation, symptomatology and family characteristics of an exclusively adolescent sample of patients with borderline personality disorder (BPD) was undertaken. Twenty-four cases of borderline personality disorder, 20 females, 4 males, identified using chart review and meeting the criteria of the Diagnostic Interview for Borderlines (DIB) and DSM III-R, were matched with psychiatric controls. Adolescents with borderline personality disorder were found to have high rates of affective symptomatology with Axis I diagnosis of major depressive disorder - MDD (DSM-III-R), and high rates of interpersonal psychopathology, i.e., manipulation, devaluation, and a pervasive sense of boredom. The latter seem to be characteristic as for adults with borderline personality disorder. The families were particularly angry and volatile.  相似文献   

18.
Cortisol levels and depression in men and women using heroin and cocaine   总被引:1,自引:0,他引:1  
Abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are well documented in men using illicit drugs and/or infected with HIV; however, less is known about HPA function, or the health consequence of HPA dysfunction, in their female counterparts. People with depression exhibit hypercortisolemia, and depression is common in people with HIV or substance use problems. The current study investigated cortisol secretion in 209 demographically matched men and women, stratified by their HIV and drug use status. Self-reported depressive symptoms were evaluated using a standardized, validated questionnaire (CES-D). Women reported more depressive symptoms than men (p=.01). Male and female drug users exhibited higher cortisol concentrations (p=.03), and were more likely to report depressive symptoms (p=.04), than non-users. Depression was related to elevated cortisol concentrations for the study population (p=.03), and women with elevated cortisol concentrations were significantly more depressed than all other participants (p=.05). While it is unknown whether high cortisol concentrations precede depressive symptoms or vice versa, these data indicate that higher cortisol concentrations are associated with depressive symptoms in heroin and cocaine users, and that this association is more pronounced in women than men. HIV status did not act in an additive or synergistic way with drug use for either cortisol or CES-D measures in the current study. Unique therapies to treat the endocrine and mental health consequences of illicit drug use in men and women deserve consideration as depressive symptoms, and high cortisol concentrations associated with depressive symptoms, differ by gender.  相似文献   

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概述:一致性(agreement)和相关性(correlation)是两个广泛使用的概念,用来评估变量之间的关联。虽然二者相似且相关,但是它们代表关联完全不同的概念。评估变量之间的一致性假设变量测量的是相同的结构,而在变量测量完全不同的结构时也可以评估它们之间的相关性。这种概念上的差异就要求使用不同的统计方法,并且当评估一致性或相关性时,统计方法根据数据的分布和研究者的兴趣可能会有所不同。例如, Pearson相关性,作为评估连续变量之间相关性的一种普遍测量方法,只有用于符合线性关系的变量时才能提供有用的信息;当用于不符合线性关系的变量时就无法提供准确信息甚至会产生误导。同样地,内部相关性,作为一种评估连续变量之间一致性的常用方法,如果一致性不好的实质正好是研究兴趣所在,那么该测量就不能为研究者提供充分的信息。本报告回顾了一致性和相关性的概念,并讨论了几种常用方法在应用中的差异。  相似文献   

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