神经细胞营养因子与运动神经元的存活和凋亡

文章就神经营养因子有选择性地保障神经元健康存活,防止凋亡和损伤所引起的神经元退变及促进再生等生物学效应,和神经营养因子效应及神经细胞,运动神经元存活,凋亡及其特征等方面研究进行综述,并对该领域中研究的新进展摘要说明.

营养神经细胞药物治疗小儿脑瘫临床疗效观察

目的:探讨营养神经细胞药物单唾液酸四己糖神经节苷脂和鼠神经生长因子治疗小儿脑瘫的临床疗效。方法:选取我院儿童康复科2012年6月~2015年6月确诊的小儿脑瘫160例,随机分为对照组80例,观察组80例。对照组采用综合的康复方法,观察组在此方法基础上应用单唾液酸四己糖神经节苷脂和注射用鼠神经生长因子这两种营养神经细胞药物,连续运用3个月。结果:治疗3个月后,对治疗效果进行评定,观察组总有效率为96.25%,对照组总有效率为93.75%,差异无统计学意义(P>0.05)。结论:单唾液酸四己糖神经节苷脂和鼠神经生长因子这两种营养神经细胞药物对脑瘫的治疗是没有疗效的,建议对脑瘫的治疗以中国脑性瘫痪康复指南为指导,以功能训练、言语训练、推拿等理学方法为主,不需应用营养神经细胞药物。

营养神经细胞药物治疗小儿脑损伤的临床疗效观察

目的:观察营养神经细胞药物治疗小儿脑损伤的临床疗效。方法:选取我院收治的脑损伤患儿90例,以随机数字表法分组,对照组(n=45)给予脑活素治疗,观察组(n=45)予以营养神经细胞药物治疗。对比两组治疗效果及症状改善时间,并比较治疗前、治疗4个疗程后两组新生儿神经行为功能评分和发育商(DQ)评分。结果:观察组总有效率高于对照组[86.67%(39/45)比68.89%(31/45)],差异有统计学意义(P<0.05);治疗4个疗程后,观察组神经行为功能、DQ评分较对照组高,差异明显(P<0.05)。结论:给予脑损伤患儿营养神经细胞药物治疗,能有效修复神经细胞,提高发育商,疗效确切。

低能量体外冲击波治疗对勃起功能障碍患者阴茎海绵体内细胞因子表达的影响

目的分析低能量体外冲击波疗法(Li-ESWT)对勃起功能障碍(ED)患者阴茎海绵体中血管内皮生长因子(VEGF)、血管生成素1(ANG-1)、血管生成素2(ANG-2)、脑源性神经细胞营养因子(BDNF)表达的影响,并探讨其可能作用机制。方法选取2021年1月至6月河南省人民医院男科门诊诊治的40例ED患者作为研究对象。随机分为试验组和对照组,每组20例。试验组在Li-ESWT治疗前1d及治疗后第1d和治疗后第3d相同时间段取阴茎海绵体血液;对照组在假治疗前后的取血时间点同试验组。检测两组VEGF、ANG-1、ANG-2、BDNF的表达水平,分析Li-ESWT治疗对ED患者阴茎海绵体血液中VEGF、ANG-1、ANG-2、BDNF表达水平的影响。结果整体分析结果显示,VEGF、ANG-1表达水平组间、时点及交互比较,差异具有统计学意义(P<0.05)。与治疗前1d相比,治疗后第1d、第3d的VEGF、ANG-1表达水平上升,差异具有统计学意义(P<0.05);治疗后第1d、第3d的ANG-2、BDNF表达水平与治疗前1d相比,差异无统计学意义(P>0.05)。与对照组相比,治疗后第1d、第3d试验组VEGF、ANG-1表达水平显著提高,差异具有统计学意义(P<0.05)。结论Li-ESWT治疗可以提高ED患者阴茎海绵体内VEGF、ANG-1的表达水平,Li-ESWT可能通过促进VEGF、ANG-1的表达来促进神经血管的再生和(或)修复来改善ED患者的勃起功能。

卵巢子宫内膜异位囊肿患者血清VEGF、BDNF水平变化及预测妊娠结局价值

目的:探讨卵巢子宫内膜异位囊肿患者血清血管内皮生长因子(VEGF)和脑源性神经细胞营养因子(BDNF)水平异常表达对妊娠结局的预测价值。方法:收集2018年3月-2020年1月本院收治的卵巢囊肿患者152例作为囊肿组,健康体检女性100例作为对照组,采集囊肿组入院时、对照组体检时血清检测VEGF和BDNF水平,统计两组及不同囊肿疾病分期患者的妊娠结局,采用受试者工作特征曲线(ROC)分析上述指标预测囊肿患者妊娠结局价值。结果:外周血VEGF、BDNF水平,囊肿组(406.35±123.27 pg/ml、1079.22±209.32 ng/L)均高于对照组(305.27±100.34 pg/ml、659.34±100.24 ng/L),且随着疾病分期增加两项指标水平升高,未受孕者均高于受孕者、劣质胚胎者高于优质胚胎、未流产者低于自然流产者、良好妊娠者低于不良妊娠(均P<0.05);ROC曲线分析显示,VEGF和BDNF预测卵巢子宫内膜异位囊肿患者妊娠结局的AUC分别为0.748(95%CI 0.606~0.890)、0.720(95%CI 0.581~0.859),预测妊娠结局的临界值分别为406.845 pg/ml、992.071 ng/L,此时的预测敏感度分别为68.4%、42.8%,特异度分别为68.0%、88.0%,两项联合的AUC为0.919(95%CI 0.872~0.966),敏感度93.8%,特异度30.5%。结论:卵巢子宫内膜异位囊肿患者外周血VEGF、BDNF水平异常升高,且随着疾病分期的增加而升高,早期检测可辅助临床预测患者妊娠,且联合检测的诊断价值更高。

亚低温联合中药治疗重型颅脑损伤疗效观察

目的探讨亚低温联合中药治疗重型颅脑损伤的临床效果。方法将重型颅脑损伤患者170例采用随机数字表法分为观察组与对照组各85例,对照组给予常规微创血肿清除术与中药治疗,观察组在此基础上加用亚低温治疗。结果治疗后观察组有效率为94.1%,对照组为78.8%,2组比较差异有统计学意义(P<0.05)。治疗后2组的NIHSS评分与颅内压均较治疗前下降,差异有统计学意义(P<0.05),2组间差异亦有统计学意义(P<0.05)。2组治疗后血清脑源性神经细胞营养因子(BDNF)含量均呈上升趋势,差异有统计学意义(P<0.05),2组间差异亦有统计学意义(P<0.05)。2组治疗后出血量和水肿带呈下降趋势,差异有统计学意义(P<0.05),2组间差异亦有统计学意义(P<0.05)。结论亚低温联合中药治疗重型颅脑损伤能有效降低颅内压与减轻脑水肿、脑出血,发挥神经保护作用,从而提高治疗疗效,作用机制可能与提高脑源性神经细胞营养因子表达有关。

注射用丹参多酚酸在卒中后抑郁中作用的研究进展

卒中后抑郁(PSD)是急性脑血管损伤后发生的一种最常见的情感障碍疾病,它会增加卒中的致死率、致残率与复发率,给家庭和社会带来了沉重的负担。PSD病因学尚不明确,涉及到一系列复杂的机制,炎性反应、细胞凋亡、神经营养因子、神经递质等可能均发挥重要作用,且尚无有效治疗方法。注射用丹参多酚酸(SAFI)具有抗炎、抗氧化应激、抗凋亡作用,并可改善抑郁行为,将有望成为治疗PSD的一种新型抗抑郁药。

老年脑卒中合并抑郁患者血清miR-26b和BDNF的表达关系研究

目的探讨老年脑卒中合并抑郁患者血清miR-26b和脑源性神经细胞营养因子(BDNF)表达关系以及对老年脑卒中患者并发抑郁的预测作用。方法选取2017年8月至2018年8月收治的老年脑卒中患者95例,根据汉密尔顿抑郁量表评分标准将患者分为合并抑郁症组41例与未合并抑郁症组54例,选取同期体检健康者56例作为对照组,采用实时荧光定量PCR法(qRT-PCR)检测血清miR-26b表达水平;采用酶联免疫吸附法(ELISA)检测血清BDNF水平。结果与正常组、未合并抑郁症组相比,合并抑郁症组miR-26b水平显著升高(P<0.05),BDNF水平显著降低(P<0.05);老年脑卒中合并抑郁患者血清miR-26b与BDNF表达呈负相关(r=-0.604,P<0.05);血清miR-26b、BDNF水平预测老年脑卒中患者发生抑郁的曲线下面积分别为0.807(敏感度68.3%,特异性87.0%)、0.900(敏感度87.8%,特异性为88.9%);logistic回归分析显示,NIHSS评分>27分、血清miR-26b水平≥1.35、BDNF≤11.91 ng/ml是影响老年脑卒中患者合并抑郁的危险因素。结论老年脑卒中后抑郁患者血清miR-26 b高表达、BDNF低表达,二者表达呈负相关,检测血清miR-26 b、BDNF表达对脑卒中患者发生抑郁具有一定预测价值。

Ex vivo non-viral vector-mediated neurotrophin-3 gene transfer to olfactory ensheathing glia: effects on axonal regeneration and functional recovery after implantation in rats with spinal cord injury

Objective Combine olfactory ensheathing glia （OEG） implantation with ex vivo non-viral vector-based neurotrophin- 3 （NT-3） gene therapy in attempting to enhance regeneration after thoracic spinal cord injury （SCI）. Methods Primary OEG were transfected with cationic liposome-mediated recombinant plasmid pcDNA3.1 （＋）-NT3 and subsequently implanted into adult Wistar rats directly after the thoracic spinal cord （T9） contusion by the New York University impactor. The animals in 3 different groups received 4x 1050EG transfected with pcDNA3.1 （＋）-NT3 or pcDNA3.1 （＋） plasmids, or the OEGs without any plasmid transfection, respectively; the fourth group was untreated group, in which no OEG was implanted. Results NT-3 production was seen increased both ex vivo and in vivo in pcDNA3.1 （＋）-NT3 transfected OEGs. Three months after implantation of NT-3-transfected OEGs, behavioral analysis revealed that the hindlimb function of SCI rats was improved. All spinal cords were filled with regenerated neurofilament-positive axons. Retrograde tracing revealed enhanced regenerative axonal sprouting. Conclusion Non-viral vector-mediated genetic engineering of OEG was safe and more effective in producing NT- 3 and promoting axonal outgrowth followed by enhancing SCI recovery in rats.

Overexpression of lentivirus-mediated glial cell line-derived neurotrophic factor in bone marrow stromal cells and its neuroprotection for the PC12 cells damaged by lactacystin

Objective To construct recombinant lentiviral vectors for gene delivery of the glial cell line-derived neurotropnic factor （GDNF）, and evaluate the neuroprotective effect of GDNF on lactacystin-damaged PC12 cells by transfecting it into bone marrow stromal cells （BMSCs）. Methods pLenti6/V5-GDNF plasmid was set up by double restriction enzyme digestion and ligation, and then the plasmid was transformed into Top10 cells. Purified pLenti6/V5-GDNF plasmids from the positive clones and the packaging mixture were cotransfected to the 293FT packaging cell line by Lipofectamine2000 to produce lentivirus, then the concentrated virus was transduced to BMSCs. Overexpression of GDNF in BMSCs was tested by RT-PCR, ELISA and immunocytochemistry, and its neuroprotection for lactacystin-damaged PC12 cells was evaluated by MTT assay. Results Virus stock of GDNF was harvested with the titer of 5.6×10^5 TU/mL. After tmnsduction, GDNF-BMSCs successfully secreted GDNF to supematant with nigher concentration （800 pg/mL） than BMSCs did （less than 100 pg/mL）. The supematant of GDNF-BMSCs could significantly alleviate the damage of PC12 cells induced by lactacystin （10 μmol/L）. Conclusion Overexpression of lentivirus-mediated GDNF in the BMSCs cells can effectively protect PC12 cells from the injury by the proteasome inhibitor.

Effect of resuscitation after selective cerebral ultraprofound hypothermia on expressions of nerve growth factor and glial cell line-derived neurotrophic factor in the brain of monkey

Objective To investigate the expression of nerve growth factor （NGF） and glial cell line-derived neurotrophic factor （GDNF） in monkeys of resuscitation after selective cerebral ultraprofound hypothermia and blood flow occlusion. Methods The monkeys were immediately removed brain after death in operation of group A （identical temperature perfusion group） and group B （ultraprofound hypothermia perfusion group）. Immunohistochemical technique was used to determine frontal cellular expression of NGF and GDNF. Statistics were analyzed by ANOVA analyses with significance level at P 〈 0.05. Results The expressions of NGF and GDNF in the group B were significantly higher than those in the group A （P 〈 0.05）. Conclusion NGF and GDNF increased significantly in the monkeys of resuscitation after selective cerebral ultraprofound hypothermia and blood flow occlusion. It may be a protective mechanism for neuron survival and neural function recovery.

自拟益气活血汤加减治疗缺血性脑卒中(气虚血瘀证)的效果及对血清NGF、BDNF和血液流变学的影响

目的探讨自拟益气活血汤加减治疗缺血性脑卒中(气虚血瘀证)的效果及对血清神经生长因子(NGF)、脑源性神经细胞营养因子(BDNF)和血液流变学的影响。方法选择2020年8月至2022年8月西安市第三医院接诊的200例缺血性脑卒中(气虚血瘀证)患者为研究对象,根据随机数表法将患者分为观察组和对照组,每组100例。对照组患者采用常规西医综合治疗,观察组患者联合自拟益气活血汤加减治疗,疗程均为1个月。比较两组患者的临床疗效,以及治疗前后的血清NGF、BDNF、血液黏度、血浆黏度、红细胞比容、红细胞聚集指数,并记录两组患者治疗期间的不良反应发生情况。结果观察组患者的治疗总有效率为90.00%,明显高于对照组的80.00%,差异有统计学意义(P<0.05);治疗前,两组患者的血清NGF、BDNF水平比较差异均无统计学意义(P>0.05),治疗后,两组患者的血清NGF、BDNF水平均明显升高,且观察组患者的血清NGF、BDNF分别为(15.10±3.15)ng/L、(14.22±2.83)μg/L,明显高于对照组的(13.06±2.60)ng/L、(11.75±2.50)μg/L,差异均有统计学意义(P<0.05);治疗前,两组患者的血液黏度、血浆黏度、红细胞比容、红细胞聚集指数比较差异均无统计学意义(P>0.05),治疗后,两组患者的上述指标均明显降低,且观察组患者的上述指标分别为(4.65±0.32)mPa·s、(1.70±0.08)mPa·s、0.36±0.05、4.01±0.62,明显低于对照组的(4.91±0.67)m Pa·s、(1.83±0.10)m Pa·s、0.42±0.12、4.33±0.75,差异均有统计学意义(P<0.05);治疗期间,观察组和对照组患者的不良反应总发生率分别为6.00%、10.00%,差异无统计学意义(P>0.05)。结论自拟益气活血汤加减治疗缺血性脑卒中(气虚血瘀证)能提高患者的血清NGF、BDNF水平,改善血液流变学,临床疗效显著且安全性较高。

Effect of ciliary neurotrophic factor on activation of astrocytes in vitro

Objective To observe the activating effect of ciliary neurotrophic factor （CNTF） on astrocyte in vitro. Methods Astrocytes cultured purely from newborn rats. Cerebral cortex was raised in normal and serum deprivation condition with different concentrations （in ng/ml： 0, 2, 20, or 200） of CNTF. After cultured for 24 h, the shape and the cell cycle of astrocytes were examined by immunocytochemistry and flow cytometer, respectively. Results The immunoactivity of glial fibrillary acidic protein （GFAP） and the nuclear size of astrocytes were increased when CNTF was applied, whether cells were cultured in medium with or without serum. CNTF promoted astrocytes to enter the cell cycle in medium with serum, but had no this effect in medium without serum. Conclusion In medium without serum, astrocytes could differentiate into activated state ceils with CNTF application, but could not proliferate; in medium with serum, astrocytes could proliferate with aid of CNTF.

藻酸双脂钠佐治脑梗死40例疗效观察

目的:观察藻酸双脂钠辅助治疗脑梗死患者的临床疗效。方法:脑梗死患者80例随机分为治疗组和对照组各40例,对照组予低分子右旋糖酐治疗为主,分别配用脱水剂、血管扩张药及神经细胞营养剂。治疗组在对照组治疗的基础上,予生理盐水250m1,加藻酸双脂钠针100mg,每日静脉滴注1次,14天为1个疗程,观察治疗前后两组临床疗效、血脂、血液流变指标变化。结果:治疗组治疗后基本治愈率优于对照组,P<0.01;血脂降低平均值大于对照组,P<0.01;血液流变全血比黏度、血浆比黏度、纤维蛋白原均较对照组有明显下降,P<0.01。结论:藻酸双脂钠辅助治疗能明显提高脑梗死患者的治愈率,有效提高脑梗死患者的综合治疗效果。

纳络酮治疗急性脑梗死40例疗效观察

急性脑梗死是一种常见病和多发病，是老年人病死的主要因素之一。我院自1999年4月至2003年4月共收治急性脑梗死患者72例，运用纳络酮治疗并观察其临床治疗效果，现报道如下。

Effects of P2Y_1 receptor on glial fibrillary acidic protein and glial cell line-derived neurotrophic factor production of astrocytes under ischemic condition and the related signaling pathways

Objective The present study aimed to explore the role of P2Y1 receptor in glial fibrillary acidic protein （GFAP） production and glial cell line-derived neurotrophic factor （GDNF） secretion of astrocytes under ischemic insult and the related signaling pathways. Methods Using transient right middle cerebral artery occlusion （tMCAO） and oxygen-glucose-serum deprivation for 2 h as the model of ischemic injury in vivo and in vitro, immunofluorescence, quantitative real-time reverse transcription-polymerase chain reaction （RT-PCR）, Western blotting, enzyme linked immunosorbent assay （ELISA） were used to investigate location of P2Y1 receptor and GDNF, the expression of GFAP and GDNF, and the changes of signaling molecules. Results Blockage of P2Y1 receptor with the selective antagonist N^6-methyl-2′-deoxyadenosine 3′,5′-bisphosphate diammonium （MRS2179） reduced GFAP production and increased GDNF production in the antagonist group as compared with simple ischemic group both in vivo and in vitro. Oxygen-glucose-serum deprivation and blockage of P2Y1 receptor caused elevation of phosphorylated Akt and cAMP response element binding protein （CREB）, and reduction of phosphorylated Janus kinase2 （JAK2） and signal transducer and activator of transcription3 （STAT3, Ser727）. After blockage of P2Y1 receptor and deprivation of oxygen-glucose-serum, AG490 （inhibitor of JAK2） reduced phosphorylation of STAT3 （Ser727） as well as expression of GFAP; LY294002, an inhibitor of phosphatidylinositol 3-kinase （PI3-K）, decreased phosphorylation of Akt and CREB; the inhibitor of mitogen-activated protein kinase kinase 1/2 （MEK 1/2） U0126, an important molecule of Ras/extracellular signal- regulated kinase （ERK） signaling pathway, decreased the phosphorylation of JAK2, STAT3 （Ser727）, Akt and CREB. Conclusion These results suggest that P2Y1 receptor plays a role in the production of GFAP and GDNF in astrocytes under transient ischemic condition and the related signaling pathways may be JAK2/STAT3 and PI3-K/Akt/CREB, respectively, and that crosstalk probably exists between them.

S100B protein in the gut:The evidence for enteroglial-sustained intestinal inflammation

Glial cells in the gut represent the morphological and functional equivalent of astrocytes and microglia in the central nervous system （CNS）. In recent years, the role of enteric glial cells （EGCs） has extended from that of simple nutritive support for enteric neurons to that of being pivotal participants in the regulation of inflammatory events in the gut. Similar to the CNS astrocytes, the EGCs physiologically express the SIOOB protein that exerts either trophic or toxic effects depending on its concentration in the extracellular milieu. In the CNS, SIOOB overexpression is responsible for the initiation of a gliotic reaction by the release of pro-inflammatory mediators, which may have a deleterious effect on neighboring cells. SlOOB-mediated pro-inflammatory effects are not limited to the brain： SIOOB overexpression is associated with the onset and maintenance of inflammation in the human gut too. In this review we describe the major features of EGCs and SIOOB protein occurring in intestinal inflammation deriving from such.

针灸联合西药治疗中风恢复期随机平行对照研究

[目的]观察针灸联合西药治疗中风恢复期疗效。[方法]使用随机平行对照方法,将60例住院患者按病志号抽签简单随机分为两组。对照组30例营养神经细胞及促进脑组织功能恢复、胞二磷胆碱及脑活素等;颅内压高降颅压。治疗组30例取阳陵泉、风池、四神聪、曲池、外关、内关、合谷、丰隆、太冲、风市以及环跳,平泻、平补,留针30min;肘部拘挛加小海、三里;踝部拘挛加照海、太溪、解溪;膝部拘挛加阳谷、曲泉;手指部拘挛加后溪、八邪;烦躁加大陵、内关;言语不利加通里、哑门、廉泉;西药治疗同对照组。连续治疗10d为1疗程。观测临床症状、神经功能缺损程度评分、不良反应。连续治疗2疗程,判定疗效。[结果]治疗组痊愈14例,显效9例,有效5例,无效2例,总有效率93.33%。对照组痊愈7例,显效10例,有效8例,无效5例,总有效率83.33%。治疗组疗效优于对照组(P<0.05)。神经功能缺损程度评分两组均有明显降低(P<0.01),治疗组降低优于对照组(P<0.05)。[结论]针灸联合西药治疗中风恢复期效果显著,值得推广。

Sequence analysis and functional study of the Han Nationality glial cell line-derived neurotrophic factor transcript

Objective: To study the sequence and function of the glial cell line-derived neurotrophic factor (GDNF) transcript in subjects of Han nationality. Methods: The Han nationality GDNF transcript was amplified by RT-PCR and expressed by baculovirus expression system. Biological activity of the expressed product was measured by the primary culture of midbrain dopaminergic neurons. Results: There only existed the shorter GDNF transcript of 555 bp in the Han nationality. The secretory expression product of the shorter transcript in insect cells promoted the survival and differentiation of dopaminergic neurons. Conclusion: It is found that there is a 78 bp deletion in the Han nationality GDNF transcript compared with the reported 633 bp GDNF transcript. The 78 bp deletion does not affect the secretory expression and biological activity of GDNF mature protein.