猴脑选择性超深低温断血流复苏对细胞因子影响的实验研究

目的观察猴脑选择性超深低温断血流复苏实验前后血清中IL-2,IL-10,TNF-α,IFN-γ的动态变化,了解脑缺血后选择性超深低温复苏对猴免疫功能的影响。方法健康恒河猴10只,随机分为两血管阻断冷灌注组(4只),四血管阻断冷灌注组(4只)和常温灌注组(2只)。应用ELISA法统一测定实验前后血清中IL-2,IL-10,TNF-α,IFN-γ的浓度。结果两血管组4只恒河猴术后安全复苏并长期存活,四种细胞因子在灌注结束后较术前均明显增高(P<0.05),24h后恢复至术前水平,72h测得值与术前无显著差异(P>0.05)。常温组2只恒河猴及四血管组4只恒河猴于灌注后均未能安全复苏,全部死亡。其中四血管组与两血管组比较在灌注结束后IL-10,TNF-α增高更明显(P<0.05),IL-2,IFN-γ增高与两血管阻断冷灌注组比较无显著差异(P>0.05)。结论猴脑选择性超深低温断血流复苏可引起抗炎细胞因子与促炎细胞因子一过性增高,由于促炎因子与抑炎因子之间互相抑制,互相作用,两类因子同时增高可使细胞因子网络维持动态平衡,有利于机体免疫功能的重新建立。     

男性慢性精神分裂症患者血清脑源性神经营养因子和胶质源性神经营养因子水平及认知功能的对照研究

目的:探讨慢性精神分裂症患者血清脑源性神经营养因子(BDNF)、胶质源性神经营养因子水平(GDNF)和神经认知功能的变化及它们之间关系。方法:入组慢性精神分裂症患者57例和正常对照39名。采用阳性与阴性症状量表(PANSS)评估患者的精神症状。使用酶联免疫吸附法检测血清BDNF、GDNF蛋白水平,采用数字划消测验、连线测验(TMT)、WMS-III空间广度测验(WMS-III SST)、定步调连续加法任务测验(PASAT)、Stroop测验、木块图评估神经认知功能。结果:患者组血清BDNF水平低于对照组,差异有统计学意义(t=9.112,P0.01),患者组血清GDNF与对照组相比差异无统计学意义(t=1.513,P0.05)。患者组数字划消测验、TMT-A、TMT-B、Stroop测验、木块图、WMS-III SST逆行分、PASAT成绩均差于对照组(P0.05)。患者组血清BDNF水平与PANSS阳性症状分、数字划消测验中的错误个数呈负相关(分别为r=-0.295,P=0.026;r=-0.262,P=0.049),血清GDNF水平与Stroop色词干扰测验分呈正相关(r=0.263,P=0.048)。结论:慢性稳定期的精神分裂症患者仍存在广泛的神经认知损害。BDNF可能是精神分裂症的一种素质性标记,可能参与了患者的注意障碍。     

脑缺血诱发星形胶质细胞粒细胞集落刺激因子受体和胶质细胞源性神经营养因子的表达

目的 探讨粒细胞集落刺激因子(G-CSF)在缺血脑保护中的作用机制.方法 制作大鼠大脑中动脉栓塞模型,7 d后断头取脑做冰冻切片,用免疫荧光双标的方法观察缺血周边区与假手术组相同部位G-CSF受体、胶质细胞源性神经营养因子(GDNF)和微管相关蛋白2(MAP2)、神经胶质原酸性蛋白(GFAP)的共表达情况.结果 G-CSF受体和GDNF在正常大鼠脑内广泛表达于神经元,不表达于星形胶质细胞;但在缺血周边区,星形胶质细胞亦部分表达G-CSF受体和GDNF.在正常脑组织,大部分G-CSF受体阳性的细胞也表达GDNF.结论 脑缺血可诱导缺血周边区星形胶质细胞表达G-CSF受体和GDNF,推测缺血后的内源性神经保护作用可能与缺血周边区星形胶质细胞的G-CSF受体表达以及GDNF产生有关.     

补肾壮阳胶囊对精神分裂症模型大鼠海马胶质细胞源性神经营养因子表达的影响

目的 探讨补肾壮阳胶囊(WSKY)对地卓西平马来酸盐(MK801)建立的精神分裂症模型大鼠海马胶质细胞源性神经营养因子(GDNF)表达的影响.方法 将40只6周龄SD雄性大鼠随机分为3组:对照组(生理盐水腹腔注射+生理盐水灌胃)、模型组(M K801腹腔注射+生理盐水灌胃)及WSKY+MK801组(MK801腹腔注射+WSKY灌胃,而根据WSKY剂量的不同又分为3个亚组);各组相应处理两周后运用Western Blot和RT-PCR技术分别检测各组大鼠海马区GDNF蛋白及mRNA的表达.结果 与对照组相比较,模型组的GDNF蛋白及mRNA的表达下降,差异有统计学意义(P<0.05);而与模型组相比,WSKY+MK801组中较高剂量WSKY可致GDNF蛋白及其mRNA的表达增加,差异有统计学意义(P<0.05).结论 MK801可致大鼠海马GDNF表达减少,而补肾壮阳胶囊可上调大鼠海马GDNF的表达.     

P2Y1受体对缺血状态下星形胶质细胞产生胶质原纤维酸性蛋白与胶质细胞源性神经营养因子的影响及相关信号通路

目的研究P2Y1受体对缺血时星形胶质细胞产生胶质原纤维酸性蛋白（glial fibrillary acidic protein,GFAP）及胶质细胞源性神经营养因子（glial cell line—derived neurotrophic factor,GDNF）的影响及其相关信号通路。方法分别利用右侧大腑中动脉线拴阻塞及培养细胞缺氧无营养后恢复正常培养,造成体内、外缺血再灌注模型。用免疫荧光标记、实时定量RT—PCR、Western blotting、酶联免疫吸附试验观察P2Y1受体、GDNF定位,检测GFAP、GDNF及信号分子的表达变化。结果与单纯性缺血组比较,用选择性拈抗剂MRS2179阻断P2Y1受体后,可使体内、外星形胶质细胞产生的GFAP减少,同时使其产生GDNF增加。体外缺氧无营养并阻断P2Y1受体后：可使磷酸化蛋白激酶B（Akt）及cAMP反应元件结合蛋（cAMP response element binding protein,CREB）升高,而使磷酸化JAK2及STAT3（Ser727）降低;JAK2的抑制剂AG490在降低磷酸化STAT3（Ser727）的同时也降低GFAP表达水平;PI3-K的抑制剂LY294002可降低磷酸化的Akt及CREB;MEK1／2抑制剂U0126可同时降低磷酸化的JAK2、STAT3 （Ser727）、Akt及CREB。结论P2Y1受体参与短时性缺血时星形胶质细胞GFAP及GDNF的产生过程,相关信号途径分别为JAK2／STAT3和P13-K／AKT／CREB,并且两条途径存在串话。     

胶质细胞源性神经营养因子治疗缺血性脑血管疾病的新进展

胶质细胞源性神经营养因子(GDNF)作为转化生长因子(TGF)-β超家族成员,是1993年从B19神经胶质瘤细胞的条件培养液中纯化的具有神经营养作用的蛋白质,损伤后的中枢神经元具有可塑性,在神经营养因子作用下其再生速度及质量均显著增强.GDNF作为对抗缺血性损伤的有效保护因子,其效应的发挥依赖于与受体的结合,GDNF受体系统由两部分构成:一部分为膜外糖磷脂酰肌醇(GPI),耦联的是GDNF     

抗坏血酸联合胶质细胞源性神经营养因子诱导神经干细胞向多巴胺能神经元分化的研究

目的 研究抗坏血酸(AA)和胶质细胞源性神经营养因子(GDNF)对神经干细胞向多巴胺能神经元分化的影响.方法 从新生24h内的sD大鼠脑组织分离和培养神经干细胞,进行神经干细胞鉴定.第二代神经干细胞诱导培养基中分别给予AA或(和)GDNF,10d后终止诱导,进行DA能神经元特异性标记物酪氨酸羟化酶(TH)和多巴胺转运蛋白的免疫细胞化学检测和TH基因的RT-PCR检测.结果 各诱导组均检测到TH mRNA的表达;与对照组比较,AA及GDNF均能增加NSC向TH阳性细胞分化的比率(P<0.05);与单独运用100μmol/LAA或10ng/mlGDNF组比较,联合诱导组可明显提高NSCs向TH阳性细胞分化的比率(P<0.05).结论 AA和GDNF均能促进NSCs向DA能神经元分化,两者联合诱导后分化作用得到进一步加强.     

神经生长因子联合康复训练对脑梗死大鼠神经行为学及脑源性神经营养因子、Bax表达的影响

目的 研究神经生长因子(NGF)联合康复训练对脑梗死大鼠神经行为学及脑源性神经营养因子(BDNF)和促凋亡蛋白Bax表达的影响.方法 将72只SD大鼠随机分为对照组、NGF组、康复训练组及NGF联合康复训练治疗组(联合治疗组),每组又分为脑梗死后7d、14 d、21 d 3个亚组.采用线栓法制作脑梗死大鼠模型,NGF组制模后即予腹腔注射鼠NGF 20 μg/(kg·d);康复训练组制模后72 h给予平衡木、转棒、网屏训练;联合治疗组同时给予NGF和康复训练.各组分别于相应时间点进行神经行为学评分,采用免疫组化染色检测脑组织BDNF、Bax的表达,逆转录-PCR法检测BDNF mRNA、BaxmRNA的表达.结果 与对照组相比,NGF组、康复训练组及联合治疗组各时间点亚组的神经行为学评分均明显降低,脑组织BDNF、BDNFmRNA表达明显升高,Bax及Bax mRNA表达明显降低(均P＜0.05).与联合治疗组比较,NGF组、康复训练组各时间点亚组的神经行为学评分均明显升高,脑组织BDNF、BDNF mRNA水平明显降低,Bax、Bax mRNA表达水平明显增高(均P＜0.05).结论 NGF联合康复训练能上调BDNF、下调Bax的表达,而显著改善脑梗死大鼠的神经功能恢复.     

胶质细胞源性神经营养因子对大鼠局灶脑缺血损伤的保护作用

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。     

Rab27b对小鼠星形胶质细胞脑源性神经营养因子分泌的影响

目的 探讨 Rab27b 对小鼠星形胶质细胞脑源性神经营养因子（BDNF）分泌的影响。 方法 采用定量 PCR 和免疫荧光染色法检测 Rab27 分子的 2 个亚型 Rab27a 和 Rab27b 在野生型小鼠大 脑皮层和海马组织中的表达和分布情况。采用免疫荧光染色法检测 Rab27b 在野生型小鼠海马区星形 胶质细胞中的表达情况。采用 Western blot 方法检测Rab27b基因敲除小鼠星形胶质细胞 BDNF 和海马 区突触可塑性标志分子 PSD95 及突触素 1 的表达,ELISA 方法检测Rab27b基因敲除小鼠星形胶质细 胞 BDNF 的分泌情况,明确Rab27b基因敲除对星形胶质细胞 BDNF 分泌水平的影响。结果 定量 PCR 和免疫荧光染色结果显示,野生型小鼠大脑皮层和海马区 Rab27b 的 mRNA 水平和荧光强度均高于 Rab27a,差异均有统计学意义（均P＜ 0.01）。免疫荧光结果显示 Rab27b 与星形胶质细胞标志分子 GFAP 共表达。Western blot 结果显示Rab27b基因敲除小鼠星形胶质细胞内 BDNF 总量与野生型小鼠比较,差 异无统计学意义（P＞ 0.05）,ELISA 结果显示Rab27b基因敲除小鼠星形胶质细胞 BDNF 分泌水平低于野 生型小鼠,差异有统计学意义（P＜ 0.05）。Western blot 结果显示Rab27b基因敲除小鼠海马中 PSD95 及 突触素 1 的表达水平均低于野生型小鼠,差异均有统计学意义（均P＜ 0.01）。结论 Rab27b 调节小鼠星 形胶质细胞分泌 BDNF,改善突触可塑性。     

Variations in glial cell line-derived neurotrophic factor release from biodegradable nerve conduits modify the rate of functional motor recovery after rat primary nerve repairs

Accelerating axonal regeneration to shorten the delay of reinnervation and improve functional recovery after a peripheral nerve lesion is a clinical demand and an experimental challenge. We developed a resorbable nerve conduit (NC) for controlled release of glial cell line-derived neurotrophic factor (GDNF) with the aim of assessing motor functional recovery according to the release kinetics of this factor in a short gap model. Different types of resorbable NCs were manufactured from a collagen tube and multiple coating layers of poly(lactide-coglycolide), varying in poly(lactide-coglycolide) type and coating thickness to afford three distinct release kinetics of the neurotrophic factor. GDNF release was quantified in vitro. End-to-end suture and GDNF-free NC served as controls. Thirty-five Wistar rats underwent surgery. Motor recovery was followed from 1 to 12 weeks after surgery by video gait analysis. Morphometrical data were obtained at mid-tube level and distal to the NC. NCs were completely resorbed within 3 months with minimal inflammation. GDNF induced a threefold overgrowth of fibers at mid-tube level. However, the number of fibers was similar in the distal segment of all groups. The speed of recovery was inversely proportional to the number of fibers at the NC level but the level of recovery was similar for all groups at 3 months. The resorbable conduits proved their ability to modulate axonal regrowth through controlled release of GDNF. In relation to the dose delivered, GDNF strikingly multiplied the number of myelinated fibers within the NC but this increase was not positively correlated with the return of motor function in this model.     

无抽搐电休克对胶质源性神经营养因子的影响

目的：探讨无抽搐电休克治疗（MECT）对难治性抑郁症患者血清胶质源性神经营养因子（GDNF）的影响。方法：16例难治性抑郁症患者经MECT和40例抑郁症患者抗抑郁治疗前后分别检测血清GDNF浓度，并与30名正常者对照比较。结果：MECT及抗抑郁治疗前，难治性抑郁症组和抑郁症组血清GDNF浓度低于对照组（P〈0.01）。难治性抑郁症组中对MECT有效的患者血清GDNF浓度显著高于治疗前（P〈0.05）;而对MECT无效的患者血清GDNF浓度与治疗前相比差异无显著性。经抗抑郁药治疗8周，抑郁症组患者血清GDNF浓度也显著增高（P〈0.01）。结论：GDNF可能在MECT和抗抑郁药治疗中起了一定的作用。     

Transfection of the glial cell line-derived neurotrophic factor gene promotes neuronal differentiation简

Glial cell line-derived neurotrophic factor recombinant adenovirus vector-transfected bone marrow mesenchymal stem cells were induced to differentiate into neuron-like cells using inductive medium containing retinoic acid and epidermal growth factor. Cell viability, micro- tubule-associated protein 2-positive cell ratio, and the expression levels of glial cell line-derived neurotrophic factor, nerve growth factor and growth-associated protein-43 protein in the su- pernatant were significantly higher in glial cell line-derived neurotrophic factor/bone marrow mesenchymal stem cells compared with empty virus plasmid-transfected bone marrow mes- enchymal stem cells. Furthermore, microtubule-associated protein 2, glial cell line-derived neurotrophic factor, nerve growth factor and growth-associated protein743 mRNA levels in cell pellets were statistically higher in glial cell line-derived neurotrophic factor/bone marrow mesen- chymal stem cells compared with empty virus plasmid-transfected bone marrow mesenchymal stem cells. These results suggest that glial cell line-derived neurotrophic factor/bone marrow mesenchymal stem cells have a higher rate of induction into neuron-like cells, and this enhanced differentiation into neuron-like cells may be associated with up-regulated expression of glial cell line-derived neurotrophic factor, nerve growth factor and growth-associated protein-43.     

尼莫地平对大鼠面神经损伤的保护作用及GDNF表达的影响

目的 探讨尼莫地平对大鼠面神经损伤的保护作用及对胶质细胞源性神经生长因子(GDNF)表达的影响.方法 96只大鼠按随机数字表法分为假手术组、单纯损伤组、尼莫地平预处理组、尼莫地平后处理组,后三组建立大鼠面神经电损伤模型.应用HE染色、Western blotting等方法,观察大鼠面神经损伤后不同时期(1、3、6月)GDNF的动态表达变化及尼莫地平不同给药时间对其表达的影响.结果 与单纯损伤组相比,尼莫地平预处理组大鼠面神经损伤程度减轻,GDNF表达升高,持续时间延长;尼莫地平预处理组GDNF表达和尼莫地平后处理组间比较差异有统计学意义(P＜0.05);尼莫地平后处理组GDNF表达在3月、6月时与单纯损伤组比较差异无统计学意义(P＞0.05).结论 预防性应用尼莫地平可以保护面神经,其机制可能是通过调节GDNF的表达而实现的.

Abstract：

Objective To study the protective function of nimodipine on facial nerve injury and its effect on the expression of glial cell line-derived neurotrophic factor (GDNF). Methods Ninety-six SD rats were randomly divided into sham-operated group, facial nerve injury group, nimodipine pretreatment group, and nimodipine post-treatment group. Rat models of facial nerve injury in thc later 3groups were established. The dynamic changes of expression of GDNF were observed by HE staining and Western blotting in different treatment groups and at different time points (1, 3 and 6 months after the injury). Restdts Compared with the facial nerve injury group, the nimodipine pretreatment and post-treatment groups had significantly less severe nerve damage and significantly up-rcgulated expression of GDNF (P＜0.05). The expression of GDNF in the nimodipine pretreatment group was statistically higher than that in the nimodipine post-treatment group (P＜0.05). However, the expression of GDNF in the nimodipine post-treatment group was not statistically different from that in the facial nerve injury group 3 and 6 months after the injury (P＞0.05). Conclusion Nimodipine has significant facial nerve protective effect, and one of the mechanisms of nimodipine to protect the facial nerve is to regulate the GDNF expression.     

Differential effects of lentiviral vector-mediated overexpression of nerve growth factor and glial cell line-derived neurotrophic factor on regenerating sensory and motor axons in the transected peripheral nerve

Even after reconstructive surgery, major functional impairments remain in the majority of patients with peripheral nerve injuries. The application of novel emerging therapeutic strategies, such as lentiviral (LV) vectors, may help to stimulate peripheral nerve regeneration at a molecular level. In the experiments described here, we examined the effect of LV vector-mediated overexpression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) on regeneration of the rat peripheral nerve in a transection/repair model in vivo. We showed that LV vectors can be used to locally elevate levels of NGF and GDNF in the injured rat peripheral nerve and this has profound and differential effects on regenerating sensory and motor neurons. For sensory neurons, increased levels of NGF and GDNF do not affect the number of regenerated neurons 1 cm distal to a lesion at 4 weeks post-lesion but do cause changes in the expression of markers for different populations of nociceptive neurons. These changes are accompanied by significant alterations in the recovery of nociceptive function. For motoneurons, overexpression of GDNF causes trapping of regenerating axons, impairing both long-distance axonal outgrowth and reinnervation of target muscles, whereas NGF has no effect on these parameters. These observations show the feasibility of combining surgical repair of the transected nerve with the application of viral vectors. Furthermore, they show a difference between the regenerative responses of motor and sensory neurons to locally increased levels of NGF and GDNF.     

Dissociation between short-term increased graft survival and long-term functional improvements in Parkinsonian rats overexpressing glial cell line-derived neurotrophic factor

The present study was designed to analyse whether continuous overexpression of glial cell line-derived neurotrophic factor (GDNF) in the striatum by a recombinant lentiviral vector can provide improved cell survival and additional long-term functional benefits after transplantation of fetal ventral mesencephalic cells in Parkinsonian rats. A four-site intrastriatal 6-hydroxydopamine lesion resulted in an 80-90% depletion of nigral dopamine cells and striatal fiber innervation, leading to stable motor impairments. Histological analysis performed at 4 weeks after grafting into the GDNF-overexpressing striatum revealed a twofold increase in the number of surviving tyrosine hydroxylase (TH)-positive cells, as compared with grafts placed in control (green fluorescent protein-overexpressing) animals. However, in animals that were allowed to survive for 6 months, the numbers of surviving TH-positive cells in the grafts were equal in both groups, suggesting that the cells initially protected at 4 weeks failed to survive despite the continued presence of GDNF. Although cell survival was similar in both grafted groups, the TH-positive fiber innervation density was lower in the GDNF-treated grafted animals (30% of normal) compared with animals with control grafts (55% of normal). The vesicular monoamine transporter-2-positive fiber density in the striatum, by contrast, was equal in both groups, suggesting that long-term GDNF overexpression induced a selective down-regulation of TH in the grafted dopamine neurons. Behavioral analysis in the long-term grafted animals showed that the control grafted animals improved their performance in spontaneous motor behaviors to approximately 50% of normal, whereas the GDNF treatment did not provide any additional recovery.     

Secretion of nerve growth factor,brain-derived neurotrophic factor,and glial cell-line derived neurotrophic factor in co-culture of four cell types in cerebrospinal fluid-containing medium

The present study co-cultured human embryonic olfactory ensheathing cells, human Schwann cells, human amniotic epithelial cells and human vascular endothelial cells in complete culture medium- containing cerebrospinal fluid. Enzyme linked immunosorbent assay was used to detect nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor secretion in the supernatant of co-cultured cells. Results showed that the number of all cell types reached a peak at 7-10 days, and the expression of nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor peaked at 9 days. Levels of secreted nerve growth factor were four-fold higher than brain-derived neurotrophic factor, which was three-fold higher than glial cell line-derived neurotrophic factor. Increasing concentrations of cerebrospinal fluid (10%, 20% and 30%) in the growth medium caused a decrease of neurotrophic factor secretion Results indicated co-culture of human embryonic olfactory ensheathing cells, human Schwann cells human amniotic epithelial cells and human vascular endothelial cells improved the expression of nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor. The reduction of cerebrospinal fluid extravasation at the transplant site after spinal cord injury is beneficial for the survival and secretion of neurotrophic factors from transplanted cells.     

氟西汀对大鼠星形胶质细胞分泌的胶质源性神经营养因子的影响

目的 探讨氟西汀对大鼠星形胶质细胞分泌的胶质源性神经营养因子(GDNF)的影响.方法 以氟西汀干预体外培养的大鼠海马星形胶质细胞,通过四甲基偶氮唑盐法(MTT)检测不同浓度氟西汀对细胞活力的影响;采用酶联免疫吸附测定法(ELISA)检测细胞培养液GDNF浓度及Real-time PCR法检测GDNFmRNA的表达.结果 (1)氟西汀浓度超过35 μmol/L浓度时,可降低细胞活性,差异有统计学意义(P<0.01或P<0.05);(2)10 μmol/L氟西汀干预星形胶质细胞不同时间后,48 h组细胞培养液GDNF浓度[(68±13)fg/L]高于0 h组[(32±11)fg/L]、6 h组[(34±12)fg/L]、12 h组[(41±17)fg/L]、24 h组[(45±13)fg/L],差异均有统计学意义(P均<0.01);(3)不同浓度氟西汀作用星形胶质细胞48 h后,10 μmol/L浓度组的细胞培养液GDNF浓度[(64±17)fg/L]高于0 μmol/L[(39±15)fg/L]和1 μmoVL浓度组[(39±18)fg/L],差异均有统计学意义(P均<0.05);(4)氟西汀作用星形胶质细胞48 h后,撤离氟西汀24 h后星形胶质细胞仍明显分泌GDNF,差异有统计学意义(P<0.01或P<0.05);(5)不同浓度氟西汀作用星形胶质细胞24 h后,10 μmol/L和20 μmol/L浓度组细胞GDNFmRNA表达量[分别为(0.008 1±0.001 1)和(0.006 3±0.000 3)]高于0 μmol/L、1 μmol/L及5 μmol/L浓度组[分别为(0.003 1±0.000 7)、(0.003 9±0.000 3)和(0.004 1±0.000 2)],差异均有统计学意义(P均<0.01).结论 氟西汀可能通过促进星形胶质细胞GDNF的分泌来发挥其神经保护作用.     

胶质细胞系源性神经营养因子对帕金森病大鼠黑质钙结合蛋白表达的影响

目的研究胶质细胞系源性神经营养因子(GDNF)对帕金森病(PD)大鼠黑质钙结合蛋白(CB)表达的影响,以及神经细胞黏附分子(NCAM)在其中的作用。方法制作PD模型大鼠36只,分为GD-NF组、NCAM阻断组和对照组,每组12只。采用免疫组化染色和免疫印迹法,检测各组大鼠黑质CB阳性细胞数和CB表达量。结果GDNF组黑质处CB阳性神经元数(46.50±6.28)及表达量(33770.60±6929.76)明显高于对照组[(27.00±8.60)、(18281.00±5266.78)](均P<0.05);与NCAM阻断组[(44.00±13.37)、(30857.00±7484.87)]相比差异无统计学意义(均P>0.05)。结论GDNF可上调PD大鼠黑质CB的表达,从而保护受损的多巴胺能神经元,NCAM对这一作用无明显影响。