The Chinese herbal formula Tongluo Jiunao promotes expression of brain-derived neurotrophic factor/tropomyosin-related kinase B pathways in a rat model of ischemic brain injury

The neurotrophin-Trk receptor pathway is an intrinsic pathway to relieve damage to the central nervous system. The present study observed the effects of Tongluo Jiunao （TLJN）, which comprises Panax Notoginseng and Gardenia Jasminoides, on expression of brain-derived neurotrophic factor （BDNF） and tropomyosin-related kinase B （TrkB） in a rat model of focal cerebral ischemic injury. Xue Sai Tong （XST）, comprising Panax Notoginseng, served as the positive control. Mechanisms of neuroprotection were analyzed following TLJN injection. Following establishment of the middle cerebral artery occlusion models, TLJN and XST were intraperitoneally injected, and 2, 3 5-triphenyltetrazolium chloride staining results revealed that TLJN injection reduced infarct volume, suggesting that TLJN exerted a neuroprotective effect. Enzyme-linked immunosorbent assay results showed that TLJN elevated BDNF and growth associated protein-43 expression in ischemic brain tissues, as well as serum BDNF levels. Reverse-transcription polymerase chain reaction and western blot results showed that TLJN injection did not affect TrkB expression in the ischemic brain tissues of rats. These results suggested that TLJN injection reduced damage to ischemic brain tissues and increased BDNF expression. In addition, TLJN injection resulted in better promoting effects on neurotrophic factor expression compared with XST.

Brain-derived neurotrophic factor protects PC12 cells from beta-amyloid-induced neurotoxicity through the tropomyosin-related kinase B receptor pathway

The present study utilized beta amyloid （Aβ）-induced cell apoptosis in PC12 cells as a cell model of Alzheimer＇s disease to investigate the interaction between brain-derived neurotrophic factor （BDNF） and the tropomyosin-related kinase B receptor. Results showed that Aβ（25-35） can reduce survival of PC12 cells and increase cleaved caspase-3 expression in PC12 cells. However, BDNF inhibited Aβ（25-35）-induced cytotoxicity and cleaved casapase-3 expression. Interestingly, pretreatment with the tropomyosin-related kinase receptor inhibitor K252a for 20 minutes prior to BDNF blocked the neuroprotective effect of BDNF on PC12 cells.

神经营养因子受体Trkb对湖羊垂体细胞增殖及促性腺激素分泌的影响

[目的]本研究旨在探究神经营养因子酪氨酸激酶B受体(Trkb)基因对湖羊垂体促性腺激素分泌的影响。[方法]利用qPCR方法对Trkb进行组织表达谱分析;构建Trkb过表达载体并转染至湖羊垂体细胞,利用qPCR、Western blot、EdU以及ELISA等技术检测过表达Trkb对垂体细胞增殖及促性腺激素分泌的影响。[结果]Trkb在湖羊心、肝、脾、肺、肾以及下丘脑和垂体等各个组织中均有表达,但在垂体中表达水平显著高于其他组织(P<0.05)。Trkb在湖羊垂体组织不同发育阶段差异表达,其中在6月龄垂体组织中高表达(P<0.05),在5日龄和3月龄表达水平较低。与对照组相比,过表达Trkb基因显著促进了垂体细胞增殖率(P<0.05),增殖标记基因Pcna表达水平与Bcl2/Bax比值均显著提高(P<0.05)。此外,过表达Trkb显著提高了促性腺激素相关基因Fshβ和Lhβ的表达水平,促进了垂体细胞促卵泡素(FSH)分泌(P<0.05)。[结论]过表达Trkb能够显著促进湖羊垂体细胞增殖,降低细胞凋亡水平从而显著提高促性腺激素的分泌水平。本研究初步验证Trkb基因在湖羊垂体细胞中功能,为深入研究Trkb调控垂体功能的分子机制提供了试验依据。

电针对甲基苯丙胺戒断后抑郁小鼠海马水通道蛋白4及BDNF/TrkB/CREB信号通路的影响

目的观察电针对甲基苯丙胺(MTHE)戒断后抑郁小鼠海马水通道蛋白4(AQP4)及脑源性神经营养因子(BDNF)/酪氨酸蛋白激酶B(TrkB)/环磷腺苷效应元件结合蛋白(CREB)信号通路的影响,探讨电针改善MTHE戒断后抑郁潜在的作用机制。方法健康雄性C57BL/6J小鼠随机分为空白组、模型组和电针组,每组10只。模型组、电针组采用条件性位置偏爱实验(CPP)复制小鼠MTHE成瘾模式,自然戒断后制备戒断后小鼠抑郁模型。空白组、模型组、电针组不给予任何干预,电针组取“百会”、“大椎”穴给予电针干预,选用连续波,频率2 Hz,1次/d,15 min/次,连续治疗28 d。分别于戒断后和干预后对各组小鼠进行强迫游泳试验和开放旷场试验,Western blot法检测小鼠海马AQP4、BDNF、TrkB、CREB和p-CREB等蛋白表达情况,免疫荧光染色法检测小鼠海马AQP4表达情况,实时荧光定量PCR法检测小鼠海马AQP4 mRNA表达。结果造模后,与空白组比较,模型组、电针组CPP值均升高(均P<0.01),模型组、电针组CPP值差异无统计学意义(P>0.05)。戒断后,与空白组比较,模型组、电针组水中自主不动状态持续时间均增加(均P<0.01)、中央区活动持续时间均减少(均P<0.01),模型组与电针组差异无统计学意义(P>0.05);干预后,与空白组比较,模型组、电针组水中自主不动状态持续时间增加(P<0.01)、中央区活动持续时间减少(P<0.01),与模型组比较,电针组水中自主不动状态持续时间减少(P<0.01),中央区活动持续时间增加(P<0.01);干预后,与空白组比较,模型组、电针组AQP4、BDNF、TrkB、CREB、p-CREB蛋白表达均减少(均P<0.01),与模型组比较,电针组AQP4、BDNF、TrkB、CREB、p-CREB蛋白表达均增加(均P<0.01)。干预后,与空白组比较,模型组、电针组AQP4阳性减少(P<0.01),与模型组比较,电针组AQP4阳性表达增加(P<0.01)。干预后,与空白组比较,模型组、电针组AQP4 mRNA表达减少(P<0.01)。干预后,与模型组比较,电针组AQP4 mRNA表达增加(P<0.01)。结论电针可改善METH戒断后小鼠抑郁样行为,其作用机制可能与调控AQP4表达,以及BDNF/TrkB/CREB信号通路活性相关。

胃癌组织中Survivin、TrkB和BDNF的表达及意义

目的观察生存素基因蛋白（Survivin）、酪氨酸激酶受体B（TrkB）及其配体脑源性神经营养因子（BDNF）在胃癌组织和癌旁黏膜中的表达情况，探讨和分析Survivin、TrkB和BDNF与胃癌临床病理学参数的关系。方法采用免疫组化sP法检测64例原发性胃癌组织、癌旁黏膜组织和34例淋巴结癌转移组中对应的阳性淋巴结Survivin、TrkB和BDNF蛋白的表达，分析其与临床病理学特征的关系。结果胃癌组织中Survivin、TrkB和BDNF蛋白的阳性表达率分别为71．87％（46／64）、60．93％（39／64）和59．37％（38／64），而癌旁黏膜组织无一例表达。Survivin、TrkB和BDNF蛋白表达与患者性别、年龄、肿瘤分化程度等无关（P〉0．05），而与浸润深度、淋巴结转移和TNM分期有关。浸润至胃壁全层组、有淋巴结转移组和TNM分期Ⅲ～Ⅳ组的Survivin、TrkB和BDNF阳性表达率明显高于未浸润至胃壁全层组、无淋巴结转移组和TNM分期Ⅰ～Ⅱ组（分别P〈0．01）。研究还显示，Survivin与TrkB和BDNF的阳性表达率随着肿瘤不同浸润深度、有无淋巴结转移呈现相同的变化趋势，相关分析表明，Survivin阳性表达与TrkB和BDNF呈正相关（P〈0．05）。胃癌转移组Survivin、TrkB和BDNF蛋白在淋巴结转移癌中的阳性表达率（82．35％，28／34；76．47％，26／34；70．58％，24／34）均较原发癌（88．23％，30／34；85．29％，29／34；82．35％，28／34）低，但两者差异无显著性（分别P〉0．05）。结论Survivin、TrkB和BDNF表达与胃癌发生发展密切相关，联合检测Survivin、TrkB和BDNF可有助于判断胃癌局部侵袭和远处转移的能力。

褪黑激素对慢性应激性抑郁症大鼠前脑皮质BDNF,TrkB表达及认知行为的影响

目的：通过观察慢性应激对大鼠认知行为的变化和前脑皮质BDNF，TrkB表达的影响，探讨褪黑激素抗抑郁作用及其机制。方法：60只SD大鼠，分为5组：空白对照组、模型对照组、褪黑激素治疗Ⅰ-Ⅲ组，每组12只。采用慢性轻度不可预见性应激和孤养方法制作抑郁症模型，腹腔注射褪黑激素加以干预，以＂T＂型迷宫试验和开场试验观察实验前后动物学习记忆能力和探究行为的变化，用免疫组化法测定前脑皮质BDNF，TrkB的表达。结果：应激刺激后，＂T＂型迷宫试验中模型对照组的错误次数多于空白对照组（P〈0.01）和褪黑激素治疗组（P〈0.01），开场试验中模型对照组的水平和直立活动次数少于空白对照组（P〈0.01）和褪黑激素治疗组（P〈0.01/P〈0.05）。前脑各层面皮质均可见到BDNF，TrkB染色阳性细胞，模型对照组阳性细胞及其灰度少于空白对照组和褪黑激素治疗组（P〈0.05/P〈0.01），褪黑激素治疗组则多于空白对照组（P〈0.01）。结论：褪黑激素能有效地促进前脑皮质神经元表达BDNF，TrkB，推测褪黑激素可能通过增强神经营养素，从而起到抑制抑郁症发作的作用。

TrkB在口腔鳞癌浸润和淋巴结转移中的功能

目的:通过实验对比口腔鳞癌(oral squamous-cell carcinoma,OSCC)与口腔正常黏膜中酪氨酸激酶受体B(tyrosine kinase B,TrkB)的表达,观察TrkB和生存基因蛋白Survivin的表达与口腔鳞癌临床病理参数之间的关系,从而了解TrkB在口腔鳞癌中的功能。方法:选用人正常口腔黏膜组织10例OSCC标本57例,采用免疫组化方法检测TrkB和Survivin的表达。结果:在口腔鳞癌中TrkB和Survivin的阳性表达率显著高于它们在正常口腔黏膜组织中的表达(P<0.05)。有淋巴结转移组和肌层浸润组的OSCC组织TrkB和Survivin的阳性表达显著高于无淋巴结转移组和黏膜及黏膜下层浸润组(P<0.05)。结论:TrkB在OSCC中呈高表达,并与Survivin联合表达,可能对OSCC的浸润和转移有促进作用。

顽固性颞叶癫痫患者海马或颞叶BDNF及其受体TrkB的测定

目的检测脑源性神经营养因子(BDNF)及其受体酪氨酸激酶B受体(TrkB)在难治性颞叶癫痫(TLE)患者颞叶和/或海马中的含量,探讨其在癫痫发病机制中的作用。方法选取经手术治疗的82例难治性TLE患者术中切除的海马或颞叶脑组织,用免疫组化方法对BDNF及其受体TrkB含量进行检测,并与11例对照进行比较。结果在难治性TLE患者中,BDNF在颞叶和海马中含量明显增加(分别P<0.05,P<0.01),且海马中含量明显高于颞叶(P<0.01);TrkB在颞叶和海马中含量显著增加(P<0.01),且海马中含量高于颞叶(P<0.05)。结论难治性TLE患者海马和颞叶中BDNF和TrkB含量增高,可能在癫痫发生、发展中起重要作用。

松果菊苷对血管性痴呆大鼠学习记忆及海马组织BDNF、TrkB表达的影响

目的通过建立血管性痴呆(VD)大鼠模型,观察松果菊苷(ECH)对VD大鼠学习记忆及海马组织脑源性神经营养因子(BDNF)、酪氨酸激酶B(TrkB)表达的影响。方法取SD大鼠随机分为假手术组、模型组和ECH组(30 mg·kg^(-1)),每组30只。采用永久性结扎双侧颈总动脉建立大鼠VD模型,ECH组给予ECH治疗4周,采用Morris水迷宫检测学习记忆能力,处死大鼠取脑,分离皮层与海马组织,HE染色观察脑组织神经元损伤。RT-PCR法测定海马组织BDNF、TrkB mRNA表达,Western blot法检测BDNF、TrkB、AKT蛋白表达水平,免疫组化法测定N-甲基-D-天冬氨酸受体(NMDAR)蛋白的表达。结果与假手术组比较,模型组大鼠逃避潜伏期延长,穿越平台次数降低(P<0.05),脑组织皮质及海马组织神经元损伤明显,海马组织BDNF、TrkB mRNA表达及BDNF、TrkB、AKT、NMDAR蛋白表达低于假手术组(P<0.05);与模型组比较,ECH组大鼠逃避潜伏期缩短,穿越平台次数增加(P<0.05),脑组织皮质及海马组织神经元损伤明显改善,海马组织BDNF、TrkB的mRNA表达及BDNF、TrkB、AKT、NMDAR蛋白表达明显高于模型组(P<0.05)。结论松果菊苷可能通过上调VD大鼠海马区BDNF、TrkB、AKT、NMDAR表达,减轻VD大鼠神经元缺血损伤,改善学习记忆能力。

BDNF/TrkB在口腔鳞癌浸润和淋巴结转移中的功能

目的:观察口腔鳞癌(oral squamous-cell carcinoma,OSCC)与口腔正常黏膜中脑源性神经生长因子(brain-derivedneurotrophic factor,BDNF)及其酪氨酸激酶受体B(tyrosine kinase B,TrkB)和生存基因蛋白Survivin的表达与口腔鳞癌临床病理参数之间的关系以及它们之间的相互关系。方法:人正常口腔黏膜组织10例,OSCC标本57例,采用免疫组化SP方法检测BDNF、TrkB和Survivin的表达。结果:BDNF、TrkB和Survivin在口腔鳞癌中的阳性表达率显著高于在正常口腔黏膜组织中的表达(P<0.05)。有淋巴结转移组和肌层浸润组的OSCC组织中TrkB、BDNF和Survivin的阳性表达显著高于无淋巴结转移组和黏膜下层浸润组(P<0.05)。TrkB与BDNF高度相关且分别与Survivin高度相关(均P<0.01)。结论:BDNF/TrkB在OSCC中呈高表达,并与Survivin联合表达,可能对OSCC的浸润和转移有促进作用。

桑芪首乌片对局灶性脑缺血再灌注大鼠BDNF及其受体TrkB表达的影响

【目的】探讨桑芪首乌片对大鼠脑缺血再灌注损伤后脑源性神经营养因子(BDNF)及其酪氨酸激酶受体B(TrkB)表达的影响。【方法】将70只SD雄性大鼠随机分为假手术对照组,模型对照组,天麻钩藤颗粒对照组(剂量为2.0 g·kg^-1·d^-1),尼莫地平片对照组(剂量为7.7 mg·kg-1·d^-1),桑芪首乌片高、中、低剂量组(生药剂量分别为2.8、1.4、0.7 g·kg^-1·d^-1),每组10只。采用线栓法建立局灶性脑缺血再灌注大鼠模型。造模后24 h内开始第1次灌胃给药,连续6周。给药结束后,观察各组大鼠神经行为学评分,采用免疫组织化学染色法观察各组大鼠脑组织BDNF、TrkB的表达。【结果】与模型对照组比较,桑芪首乌片高、中剂量组大鼠给药3周后的神经行为评分明显降低(P<0.05),桑芪首乌片高、中、低剂量组BDNF、TrkB阳性细胞数量明显增加(P<0.05),均呈剂量依赖性。【结论】桑芪首乌片能通过上调脑缺血再灌注大鼠脑组织BDNF、TrkB的表达,从而发挥神经保护作用。

卵泡液中神经营养因子4及卵丘细胞TrkB受体与卵子发育潜能的关系

【目的】探索人卵泡液中神经营养因子4(NT-4)及卵丘颗粒细胞中TrkB受体的表达与卵子发育潜能的关系。【方法】收集2020年5月至2020年11月在中山大学附属第六医院生殖中心,因男方因素行卵胞浆内单精子注射(ICSI)治疗的63例患者的卵泡液和卵丘颗粒细胞,用ELISA检测卵泡液中NT-4水平,实时荧光定量PCR检测卵丘颗粒细胞中TrkB受体两种不同亚型TrkB-fl和TrkB-t1的表达水平,分析与卵子成熟、受精和胚胎发育的关系。【结果】卵泡液中NT-4水平与正常受精数(rs=0.250,P=0.048)、可利用胚胎数(rs=0.320,P=0.011)、优质胚胎数(rs=0.327,P=0.009)和优质囊胚数(rs=0.303,P=0.029)呈正相关。卵丘颗粒细胞中TrkB-t1在高囊胚形成率组(≥60%)和高优质囊胚率组(≥50%)中的表达均较低[0.86(0.60,1.85)vs.2.29(1.09,3.44),P=0.008;0.84(0.64,1.45)vs.1.73(0.96,3.14),P=0.031]。多重线性回归分析结果示优质胚胎数受获卵数(P=0.001)、卵泡液中NT-4水平(P=0.005)和卵丘颗粒细胞TrkB-t1表达水平(P=0.049)影响。【结论】人卵泡液中NT-4水平与ICSI患者卵子发育潜能正相关,其可能在卵子发育过程中发挥着重要作用。卵丘颗粒细胞中TrkB-t1的高表达与卵子发育潜能受损有关。

低氧对BDNF和TrkB受体及其信号通路影响的研究进展

探析了急性低氧损伤与适度低氧或低氧预适应(HPC)神经保护作用的相关机制及其涉及的信号通路研究进展,回顾了脑源性神经营养因子(BDNF)、酪氨酸激酶受体B(TrkB)及BDNF/TrkB信号通路在神经生理及神经病理过程中的作用,并对急性低氧与低氧预适应分别影响BDNF、TrkB受体的表达和BDNF/TrkB信号通路的相关途径与机制进行了归纳。通过总结了解到低氧具有双重作用,既有严重缺氧导致损伤,又有适度低氧或低氧预适应对机体有益的保护作用,阐明其调节机制具有一定的参考价值。

Specific effects of c-Jun NH2-terminal kinaseinteracting protein 1 in neuronal axons

c-Jun NH2-terminal kinase（JNK）-interacting protein 3 plays an important role in brain-derived neurotrophic factor/tropomyosin-related kinase B（Trk B） anterograde axonal transport. It remains unclear whether JNK-interacting protein 1 mediates similar effects, or whether JNK-interacting protein 1 affects the regulation of Trk B anterograde axonal transport. In this study, we isolated rat embryonic hippocampus and cultured hippocampal neurons in vitro. Coimmunoprecipitation results demonstrated that JNK-interacting protein 1 formed Trk B complexes in vitro and in vivo. Immunocytochemistry results showed that when JNK-interacting protein 1 was highly expressed, the distribution of Trk B gradually increased in axon terminals. However, the distribution of Trk B reduced in axon terminals after knocking out JNK-interacting protein 1. In addition, there were differences in distribution of Trk B after JNK-interacting protein 1 was knocked out compared with not. However, knockout of JNK-interacting protein 1 did not affect the distribution of Trk B in dendrites. These findings confirm that JNK-interacting protein 1 can interact with Trk B in neuronal cells, and can regulate the transport of Trk B in axons, but not in dendrites.

Neuroprotective effects of exogenous brain-derived neurotrophic factor on amyloid-beta 1-40-induced retinal degeneration

Amyloid-beta(Aβ)-related alterations,similar to those found in the brains of patients with Alzheimer's disease,have been observed in the retina of patients with glaucoma.Decreased levels of brain-derived neurotrophic factor(BDNF)are believed to be associated with the neurotoxic effects of Aβpeptide.To investigate the mechanism underlying the neuroprotective effects of BDNF on Aβ_(1-40)-induced retinal injury in Sprague-Dawley rats,we treated rats by intravitreal administration of phosphate-buffered saline(control),Aβ_(1-40)(5 nM),or Aβ_(1-40)(5 nM)combined with BDNF(1μg/mL).We found that intravitreal administration of Aβ_(1-40)induced retinal ganglion cell apoptosis.Fluoro-Gold staining showed a significantly lower number of retinal ganglion cells in the Aβ_(1-40)group than in the control and BDNF groups.In the Aβ_(1-40)group,low number of RGCs was associated with increased caspase-3 expression and reduced TrkB and ERK1/2 expression.BDNF abolished Aβ_(1-40)-induced increase in the expression of caspase-3 at the gene and protein levels in the retina and upregulated TrkB and ERK1/2 expression.These findings suggest that treatment with BDNF prevents RGC apoptosis induced by Aβ_(1-40)by activating the BDNF-TrkB signaling pathway in rats.

TrkB and p-trkB expression in brain-derived neurotrophic factor-pretreated rat retina following acute high intraocular pressure

BACKGROUND： Exogenous brain-derived neurotrophic factor （BDNF） promotes retinal ganglion cell survival. However, the protective mechanisms remain unclear. OBJECTIVE： To investigate changes in retinal tyrosine kinase receptor B （trkB） expression and effects of exogenous BDNF on trkB activation in a rat model of acute high intraocular pressure （HtOP）. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Department of Anatomy and Neurobiology, Xiangya Medical School, Central South University from January 2004 to August 2006. MATERIALS： Rabbit anti-BDNF and anti-trkB.FL（full-length） polyclonal antibodies were purchased from Santa Cruz Biotechnology, USA; rabbit anti-p-trkB polyclonal antibodies were purchased from Cellsignal, USA. METHODS： A total of 48 healthy, adult, Sprague Dawiey rats were randomly assigned to acute HIOP （without BDNF pre-treatment） and BDNF pre-treated groups, with 24 animals in each group. In the BDNF pre-treated group, the left eyes were intravitreally injected with 3 pg/kg BDNF 2 days prior to HIOP. Rats in the acute HIOP group were not pre-treated with BDNE HIOP models were established by increased intraocular pressure in the left eyes until the b-wave of flash electroretinogragh disappeared and pressure was maintained for 60 minutes. The right eyes of all rats were not treated and served as the normal controls. MAIN OUTCOME MEASURES： Retinal structure and cell numbers in the ganglion cell layer （GCL） were detected by Nissl staining; expression of trkB and phosphorylated trkB in the rat retina were determined by immunohistochemistry. RESULTS： A greater number of GCL neurons were observed in the pre-treated group compared to the acute HIOP group （P 〈 0.05）. TrkB expression was significantly increased following HIOP at days 1 and 3 （P 〈 0.05）, but expression varied between retinal areas. Although trkB expression decreased at 7 days, phosphorylated trkB dramatically decreased with increasing time （P 〈 0.05）. TrkB expression in BDNF pre-treated rats was similar to the acute HIOP group at early injury time points. Nevertheless, trkB expression was significantly decreased compared to the acute HIOP group at 7 days （P 〈 0.05）, and phosphorylated trkB expression was significantly greater compared to the acute HIOP group at each time point （P〈 0.05）. CONCLUSION： TrkB expression displayed temporal and spatial changes in the rat retina following acute HIOP, and trkB up-regulation suggested that more BDNF was required for treating the injured retina. Exogenous BDNF partially ameliorated decreased expression of phosphorylated trkB and provided protection to the injured retina, to a certain degree, following HIOP.

TrkB抑制剂对前列腺癌细胞生物学效应及VEGF表达的影响

目的探讨酪氨酸激酶受体B(TrkB)抑制剂对前列腺癌细胞生物学效应及血管内皮生长因子(VEGF)表达的影响。方法将培养后的人前列腺癌PC3细胞分为空白对照组、酪氨酸激酶抑制剂(K252a)干预组,K252a干预组又分为150 nmol/L、300 nmol/L、450 nmol/L、600 nmol/L的4个亚组,采用四甲基偶氮唑蓝(MTT)法检测K252a对前列腺癌PC3细胞的细胞增殖抑制率;选择450 nmol/L K252a作为干预组与空白对照组比较,采用Transwell法检测2组前列腺癌PC3细胞的迁移数目,流式细胞术检测2组前列腺癌PC3细胞周期分布百分比和细胞凋亡率,Western blot检测2组前列腺癌PC3细胞中TrkB、VEGF蛋白的表达。结果4个不同浓度K252a的作用下,随着作用时间的延长,前列腺癌PC3细胞的增殖抑制率呈整体上升趋势,均高于空白组(P<0.05);K252a干预组PC3细胞24 h的迁移数目低于空白对照组(P<0.05),K252a干预组的G1期细胞比率高于空白对照组(P<0.05),K252a干预组的S期细胞比率低于空白对照组(P<0.05),K252a干预组的细胞凋亡率高于空白对照组(P<0.05),K252a干预组的TrkB、VEGF蛋白相对表达量均低于空白对照组(P<0.05)。结论K252a对前列腺癌PC3细胞增殖、迁移和生长具有抑制作用,其机制可能与K252a抑制前列腺癌细胞TrkB及VEGF蛋白的表达有关。

Glehnia fittoralis Extract Promotes Neurogenesis in the Hippocampal Dentate Gyrus of the Adult Mouse through Increasing Expressions of Brain-Derived Neurotrophic Factor and Tropomyosin-Related Kinase B

Background： Glehnia littoralis has been used for traditional Asian medicine, which has diverse therapeutic activities. However, studies regarding neurogenic effects of G. littoralis have not yet been considered. Therefore, in this study, we examined effects of G. littoralis extract on cell proliferation, neuroblast differentiation, and the maturation of newborn neurons in the hippocampus of adult mice. Methods： A total of 39 male ICR mice （12 weeks old） were randomly assigned to vehicle-treated and 100 and 200 mg/kg G. littoralis extract-treated groups （n = 13 in each group）. Vehicle and G. littoralis extract were orally administrated for 28 days. To examine neurogenic effects ofG. litmralis extract, we performed immunohistochemistry tbr 5-bromo-2-deoxyuridine （BrdU, an indicator for cell proliferation） and doublecortin （DCX, an immature neuronal marker） and double immunofluorescence staining for BrdU and neuronal nuclear antigen （NeuN, a mature neuronal marker）. In addition, we examined expressional changes of brain-derived neurotrophic factor （BDNF） and its major receptor tropomyosin-related kinase B （TrkB） using Western blotting analysis. Results： Treatment with 200 mg/kg, not 100 mg/kg, significantly increased number of BrdU-immunoreactive （＋） and DCX＋ cells （48.0 ±3.1and 72.0 ± 3.8 cells/section, respectively） in the subgranular zone （SGZ） of the dentate gyrus （DG） and BrdU＊/NeuN＋ cells （17.0 ±1.5 cells/section） in the granule cell layer as well as in the SGZ. In addition, protein levels of BDNF and YrkB （about 232% and 244% of the vehicle-treated group, respectively） were significantly increased in the DG of the mice treated with 200 mg/kg ofG. littoralis extract. Conclusion： G. littoralis extract promots cell proliferation, neuroblast differentiation, and neuronal maturation in the hippocampal DG, and neurogenic effects might be closely related to increases ofBDN F and TrkB proteins by G. littoralis extract treatment.

Tramadol reinforces antidepressant effects of ketamine with increased levels of brain-derived neurotrophic factor and tropomyosin-related kinase B in rat hippocampus

Ketamine exerts rapid and robust antidepressant properties in both animal models and depressed patients and tramadol possesses potential antidepressant effects.Brain-derived neurotrophic factor(BDNF)is an important biomarker for mood disorders and tropomyosin-related kinase B(TrkB)is a high affinity catalytic receptor for BDNF.We hypothesized that tramadol pretreatment might reinforce ketamine-elicited antidepressant effects with significant changes in hippocampal BDNF and TrkB levels in rats.Immobility time of rats receiving different treatment in the forced swimming test(FST)was observed.Levels of BDNF and TrkB in hippocampus were measured by enzyme linked immunosorbent assay.Results showed that tramadol(5 mg/kg)administrated alone neither elicited antidepressant effects nor altered BDNF or TrkB level.However,pretreatment with tramadol(5 mg/kg)enhanced the ketamine(10 mg/kg)-elicited antidepressant effects and upregulated the BDNF and TrkB levels in hippocampus.In conclusion,tramadol pretreatment reinforces the ketamine-elicited antidepressant effects,which is associated with the increased levels of BDNF and TrkB in rat hippocampus.

白松片对抑郁模型大鼠海马脑源性神经营养因子和酪氨酸激酶B表达的影响

目的采用慢性应激复制抑郁大鼠模型,观测白松片对抑郁模型大鼠海马BDNF、TrkB表达的影响,探讨白松片的抗抑郁作用机制。方法将大鼠随机分为正常组、模型组、白松片组、氟西汀组,采用连续21d慢性轻度不可预见性应激配合孤养复制抑郁模型。运用免疫组化方法研究白松片对抑郁模型大鼠海马CA1、CA3区锥体细胞和齿状回颗粒细胞BDNF、TrkB蛋白表达的影响。结果与正常组相比,模型组大鼠海马CA1、CA3区和齿状回BDNF、TrkB免疫反应阳性神经元平均灰度值上升,分别为107. 73±3. 43、119. 40±6. 36、109. 20±4. 65;与模型组相比,白松片组大鼠海马CA1、CA3区和齿状回BDNF、TrkB免疫反应阳性神经元平均灰度值下降,分别为105. 80±3. 32、109. 87±4. 82、105. 00±2. 56。结论白松片增加抑郁模型大鼠海马BDNF、TrkB的表达,可能是其抗抑郁作用的分子机制之一。