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1.
目的:研究两种钙离子通道:NMDA受体型和L-型电压门控钙通道(L-VGCC)在短暂全脑缺血复灌后海马c-Jun表达中的作用。方法:采用SD大鼠四动脉结扎全脑缺血模型,取缺血复灌不同时间(0,1,3,6,12,24和72h)以及对照组2D大鼠的海以,应用免疫印迹的方法来研究c-Jun的表达并观察几种钙通道拮抗剂对c-Jun表达的影响。结果:在假手术以及复灌的各个时间点均有表达,并在复灌6h达到高峰。氯胺酮(一种非竞争性NMDA受体拮抗剂)和硝苯吡啶(一种L-VGCC阻滞剂)抑制c-Jun表达的增加。而DNQX(一种AMPA/KA受体拮抗剂)则无抑制作用(数据未显示)。结论:缺血复灌后,c-Jun的表达增加了,这种增加与NMDA受体和L-VGCC这两种钙离子通道的开放有关。  相似文献   

2.
目的研究亚低温对大鼠全脑缺血再灌注损伤后海马CA1区神经元的保护作用,并探讨其可能的机制。方法采用四血管阻断法建立大鼠全脑缺血模型。SD大鼠,随机分为假手术组(SH组)、常温组(IR组)和亚低温组(HIR组)。各组在全脑缺血15min后分别再灌注6h、12h、1d、3d,采用苏木素-伊红(HE)染色观察各时间点海马CA1区细胞形态学变化和TUNEL法检测海马CA1区神经元凋亡,免疫印迹检测c-Jun蛋白表达。结果(1)HE染色结果 IR组和HIR组于全脑缺血再灌注后6h,HE染色未见明显改变,IR组缺血再灌注1d时CA1区出现严重改变,3d时损伤最严重,出现细胞数目减少,细胞胞体缩小、胞核固缩深染,损伤严重,排列紊乱,核膜不清,核仁消失。而HIR组海马存活的锥体细胞数较之IR组12h、1d、3d时间点均明显增加(P<0.05)。(2)TUNEL标记IR组于缺血再灌注后6h在海马CA1区阳性细胞开始增多,缺血再灌注1 d时阳性细胞数最多。而HIR组各时间点阳性细胞数均较IR组明显减少(P<0.01)。(3)免疫印迹结果全脑缺血再灌注后6h c-Jun蛋白在IR组海马CA1区表达开始增加,12h达高峰,持续到3d;HIR组在各时间点的表达均弱于IR组(P<0.01)。结论亚低温通过减少海马CA1区c-Jun的表达,抑制海马CA1区神经元的凋亡,可能是亚低温脑保护作用的机制之一。  相似文献   

3.
目的:研究脑缺血损伤诱导非受体酪氨酸蛋白激酶Src之丝、苏、酪氨酸残基磷酸化及其与Pyk2结合的变化并探讨其可能的调节机制.方法:四动脉结扎模型诱导大鼠前脑缺血损伤,免疫沉淀和免疫印迹法观察Src氨基酸残基磷酸化及其与Pyk2结合的变化.结果:缺血15 min后复灌,Src的Tyr-416和Ser而不是Thr的磷酸化有明显增加,且复灌6h Tyr416磷酸化升至最高,而Ser磷酸化1 h升至顶峰,它们分别是正常组的2.8和2.3倍;此外,缺血/复灌明显诱导Src与Pyk2的结合,相似于Tyr-416磷酸化变化,复灌6 h升至最高.50mg/kg的氯胺酮能明显抑制缺血/复灌诱导的Src Tyr-416磷酸化及其与Pyk2结合增加,与对照组比有显著性差异(P<0.05).结论:脑缺血诱导了Src蛋白激酶Ser和Tyr-416磷酸化及其与Pyk2结合,它们参与了Src的激活和NMDA受体功能的自调.  相似文献   

4.
钙离子拮抗剂治疗中风的研究   总被引:1,自引:0,他引:1  
一、钙通道的分子生物学研究细胞外液的钙离子浓度约为10~(-3)mol/L,而细胞内液为10~(-6)mol/L,其浓度梯度的维持主要靠三种互相依赖的系统调节:电压依赖性钙通道、受体或神经递质依赖的钙通道和第二信使调节的内部途径。最近的研究表明有三种不同类型的电压依赖性钙通道:T型、L型和N型。T通道开放的时间短暂,很快失活;L通道的开启产生持续的钙内流;N通道则具有区别于T、L型通道的独特性质,并且只存在于某些神经元上。三种通道中只有L型通道对经典的钙拮抗剂敏感。二、钙离子拮抗制的药理钙离子拮抗剂和无活性的L型电压依赖性钙通道结合引起构型变化后限制钙离子经该通道进入细胞内。在高浓度情况下钙离子拮抗剂也可以抑制钙离子经受体依赖性钙通道进入细胞内。药理剂量的  相似文献   

5.
目的 :研究脑缺血损伤诱导非受体酪氨酸蛋白激酶Src之丝、苏、酪氨酸残基磷酸化及其与Pyk2结合的变化并探讨其可能的调节机制。方法 :四动脉结扎模型诱导大鼠前脑缺血损伤 ,免疫沉淀和免疫印迹法观察Src氨基酸残基磷酸化及其与Pyk2结合的变化。 结果 :缺血 15min后复灌 ,Src的Tyr 4 16和Ser而不是Thr的磷酸化有明显增加 ,且复灌 6hTyr 4 16磷酸化升至最高 ,而Ser磷酸化 1h升至顶峰 ,它们分别是正常组的 2 .8和 2 .3倍 ;此外 ,缺血 /复灌明显诱导Src与Pyk2的结合 ,相似于Tyr 4 16磷酸化变化 ,复灌 6h升至最高。 5 0mg/kg的氯胺酮能明显抑制缺血 /复灌诱导的SrcTyr 4 16磷酸化及其与Pyk2结合增加 ,与对照组比有显著性差异 (P <0 .0 5 )。结论 :脑缺血诱导了Src蛋白激酶Ser和Tyr 4 16磷酸化及其与Pyk2结合 ,它们参与了Src的激活和NMDA受体功能的自调。  相似文献   

6.
兴奋性氨基酸在缺血性海马神经元损害中的作用的研究   总被引:7,自引:0,他引:7  
采用大鼠全脑缺血模型,研究脑缺血再灌流海马氨基酸含量的动态变化及相应病理改变,观察NMDA(N-甲基-D-门冬氮酸)受体拮抗剂MK-801的疗效,提示兴奋性氨基酸(Glu,Asp)可能参与海马神经元损害,MK-801能有效防止海马CA_1区迟发性神经元坏死。兴奋性氨基酸受体拮抗剂的研究,将为临床缺血性中风治疗提供新的途径。  相似文献   

7.
目的观察缺血后处理对大鼠全脑缺血再灌注损伤的神经保护作用,并探讨NMDA受体在该过程中的作用。方法采用4-VO法制备全脑缺血模型,将30只SD大鼠完全随机分为假手术组(S组)、全脑缺血(15 min)再灌注组(I/R组)、缺血后处理组(15 s/15 s,3cycle)(IP组)、NMDA受体阻滞剂MK-801预处理组(IP+MK-801组)、NR2B选择性受体阻滞剂ifenprodil预处理组(IP+ifenprodil组),以水迷宫、旷场实验及神经功能缺损评分评价其对行为学的影响,以尼氏染色法观察大鼠海马CA1区存活细胞的变化。结果与全脑缺血组大鼠相比,缺血后处理组大鼠逃避潜伏期缩短,穿越平台增加,旷场试验评分及神经功能缺陷评分更低,病理形态学改变减轻,每250μm存活神经元数增多,差异均有统计学意义(P<0.05);上述改变均被MK-801阻断,与缺血后处理组有统计学差异(P<0.05),IP+ifenprodil组的表现与缺血后处理组未见差异。结论 NMDA受体可能参与缺血后处理对全脑缺血大鼠的神经保护作用。  相似文献   

8.
目的采用大鼠全脑缺血再灌注(I/R)模型,观察1-磷酸鞘氨醇(S1P)受体激动剂芬戈莫德(FTY720)对海马组织Ca2+/CaM依赖的蛋白激酶的激酶CaMKK表达水平和Akt磷酸化水平的影响以及对缺血再灌注后神经元的保护作用。方法制备全脑缺血大脑四动脉结扎模型,采用免疫印迹技术检测FTY720和CaMKK抑制剂STO-609对缺血后海马CA1区CaMKK表达、Akt磷酸化水平的影响,采用TUNEL检测FTY720和STO-609对缺血后海马神经元凋亡的影响。结果 FTY720降低缺血后海马CA1区神经元凋亡细胞数(P<0.05),而且在缺血复灌1d提高了CaMKK表达水平、Akt磷酸化水平(P<0.05),而STO-609可以降低其两者升高的水平(P<0.05)。结论 FTY720对缺血复灌后神经元有抗凋亡作用而且可能的分子机制是激活了CaMKK/Akt信号通路。  相似文献   

9.
目的:探讨大鼠脑缺血再灌注损伤后,海马CAl区锥体细胞caspaso-3表达及细胞凋亡的变化及使用钾通道拮抗剂IBTX(ibetiotoxin)的保护作用及其保护机制。方法:通过腹腔注射硝普钠加双侧颈总动脉夹闭建立大鼠全脑缺血一再灌模型,侧脑室注射IBTX,免疫组化法测caspase-3表达情况,TUNEL法检测细胞凋亡。结果:大鼠全脑缺血-再灌注24小时后,海马CAl区锥体细胞caspase-3阳性表达,TUNEL法检测有细胞凋亡,在用药IBTX组,caspase-3阳性表达减少,TUNEI法检测细胞凋亡亦有明显降低。结论:大鼠全脑缺血-再灌注24小时后海马CAl区锥体细胞出现细胞凋亡,使用钾通道拮抗剂IBTX可减少细胞凋亡的发生,从而发挥保护作用。  相似文献   

10.
目的 通过观察大鼠缺血脑组织中Na(v)1.6表达探讨Na(v)1.6与缺血性脑损伤的关系.方法 线栓法制作大鼠脑缺血模型,168只SD大鼠分为假手术组、脑缺血组和钠通道阻滞剂-riluzole、钙通道阻滞剂-nimodipine治疗组.大鼠脑缺血后6h、1d、2d、3d取材,应用免疫组化检测Na(v)1.6表达,荧光法检测钙离子浓度,氯化三苯四唑染色检测脑梗死体积.结果 Na(v)1.6在脑缺血后6h~1d表达上调,2~3d表达下调;相同时间点nimodipine治疗组与缺血组相比较,Na(v)1.6表达变化不明显;riluzol治疗组Na(v)1.6表达变化明显,差异具有显著性(P<0.05).riluzol治疗组和nimodipine治疗组钙离子浓度、脑梗死体积均比缺血组降低,riluzol治疗组降低最明显,差异具有显著性(P<0.05).结论 钠离子内流发生在脑缺血的早期阶段;脑缺血后Na(v)1.6表达上调,抑制Na(v)1.6表达可以减轻脑缺血损伤,Na(v)1.6参与了缺血性脑损伤.  相似文献   

11.
目的:探讨雌激素(E)和姜黄素(C)影响癫发作的机制。方法:用E和C单独及联用连续处理去势雌性大鼠5d,第6天以海人酸(KA)杏仁核点燃法制备癫大鼠模型,观察大鼠癫发作的行为学表现,用免疫组化方法检测海马组织c-Jun蛋白的表达。结果:E加C组(EC KA组)大鼠癫重度发作的严重程度较E组(E KA组)明显减轻(P<0.05)。E KA组海马中c-Jun蛋白表达最多,C组(C KA组)及对照组(KA组)均表达较少且没有任何差异;EC KA组海马的CA1区c-Jun蛋白表达较E KA组明显减少(P<0.05)。结论:C能一定程度上减轻E引起的癫发作加重,它可能通过抑制c-Jun/核转录因子激活蛋白-1(activate-protein1,AP-1)活性,使E作用的AP-1通路受阻,从而减轻了E的促神经元兴奋作用。  相似文献   

12.
目的探讨尼莫地平能否诱导小脑颗粒神经元凋亡及可能机制。方法取Sprague-Dawley(SD)大鼠小脑颗粒神经元,体外培养7d,用含10μM尼莫地平培养基处理神经元24h,对照组为含1‰二甲亚砜(DMSO)培养基处理细胞。Hoechst33258染胞核检测凋亡率。Westernblot检测c-Fos和c-Jun蛋白的表达水平;腺病毒作载体过表达c-Fos和负显性c-Jun突变体阻断c-Jun功能,检测能否抑制尼莫地平诱导的神经元凋亡,免疫细胞化学方法检测腺病毒感染率。结果对照组神经元的凋亡率为(10±4)%,尼莫地平处理6、12、24h后神经元的凋亡率分别为(13±4)%、(28±5)%、(45±3)%。尼莫地平处理使c-Fos表达下调,但c-Jun表达水平上调。腺病毒Ad-c-Fos和Ad-c-JunDN(负显性c-Jun突变体)对神经元感染率为85%以上,过表达c-Fos或负显性c-Jun突变体使尼莫地平诱导的神经元凋亡率从(42±6)%减少到(28±6)%或(20±3)%。结论尼莫地平通过下调c-Fos和上调c-Jun表达诱导小脑颗粒神经元凋亡。  相似文献   

13.
颅内动脉瘤组织超微结构及MMP-9表达相关调控机制的研究   总被引:1,自引:0,他引:1  
目的 探讨颅内动脉瘤组织超微结构及MMP-9过度表达的相关调控机制.方法 观察颅内动脉瘤标本和正常脑血管的血管壁细胞外基质的形态学变化,检测脑血管壁组织内的CD68、MMP-gmRNA表达水平及c-Jun免疫活性,进行相关统计学分析.结果 电镜下见颅内动脉瘤血管壁的内皮细胞、平滑肌细胞凋亡和细胞外基质(ECM)破坏,CD68在颅内动脉瘤组织内14.60±1.72/高倍视野,正常脑血管壁内未见CD68阳性表达(P<0.01);c-Jun免疫活性在颅内动脉瘤组织内为1.92±051,正常脑血管壁内为0.17±0.41(P<0.01);动脉瘤组织中MMP-9mRNA的表达是正常对照的10.06倍(P<0.01);CD68和MMP-9mRNA之间呈显著正相关(r<,1>=0.931);颅内动脉瘤组织内c-Jun和MMP-9mRNA之间呈显著正相关(r<,2>=0.818).结论 颅内动脉瘤瘤壁组织中阳性表达的CD68可能通过激活c-Jun进而诱导MMP-9的大量表达破坏ECM参与颅内动脉瘤的发病机制.  相似文献   

14.
目的检测c-Jun在颅内动脉瘤中的表达及探讨其对基质金属蛋白酶-9(MMP-91表达调控的意义。方法对15例颅内动脉瘤标本和6例非脑血管病患者的正常脑血管应用免疫组化SP法和实时荧光定量RT-PCR法分别检测脑血管壁组织内c-Jun免疫活性和MMP-9mRNA的表达水平。结果c-Jun免疫活性在颅内动脉瘤壁组织内为1.92±0.51,正常脑血管壁内为0.17±0.41,二者有显著性差异(P〈0.01)。动脉瘤壁组织中MMP-9mRNA的表达是正常血管的10.06倍(P〈0.01)。颅内动脉瘤壁组织内c-Jun的免疫活性和MMP-9mRNA的表达呈正相关(r=.818,P〈0.001)。结论活化后的c-Jun可能通过其结构域内MMP-9结合位点启动MMP-9大量转录而参与颅内动脉瘤的发病机制。  相似文献   

15.
A polyclonal antibody intended to recognize c-Jun (Oncogene Science, c-jun/AP-1, Ab-2) has previously been shown to recognize an apparently novel “apoptosis-specific protein” (ASP) in the cytoplasm of cells undergoing apoptotic cell death in vitro. We have investigated whether this antibody would also serve as a reliable marker for apoptotic motoneurons in vivo. Following transection of the left facial nerve in anesthetized neonatal rat pups, which results in over 90% death of the facial motoneurons, we performed immunohistochemistry on frozen brain stem sections with Oncogene Science Ab-1 and Ab-2 antibodies which are raised against different peptide fragments of c-Jun. While Ab-1/c-Jun labelling was seen in the nuclei of the majority of axotomized motoneurons, Ab-2/ASP immunoreactivity was present only in scattered cells, all of which had characteristic apoptotic morphology. Furthermore, Ab-2/ASP immunoreactivity was cytoplasmic and frequently included the dendrites and axons of dying neurons. Some cerebellar granule cells undergoing postnatal developmental cell death were also Ab-2/ASP positive. The time course of the number of Ab-2/ASP-labelled motoneurons corresponded relatively closely with our previous data on DNA fragmentation in these cells, as assessed by an in situ end labelling (ISEL) technique. When facial nerve axotomy was performed at 7 and 14 days postnatum, resulting in reduced cell death, the number of Ab-2/ASP immunoreactive cells decreased correspondingly. Although the exact identity of the epitope recognized by Ab-2 is unclear, we conclude that, by labelling the cytoplasmic and neuritic components of apoptotic motoneurons, Ab-2/ASP immunohistochemistry is a valuable complementary technique to existing in situ methods based on the detection of fragmented DNA in the cell nucleus. Received: 28 July 1997 / Revised, accepted: 1 October 1997  相似文献   

16.
目的检测孤独症谱系障碍(ASD)患儿的c-Jun氨基末端激酶(JNK)通路蛋白表达情况,探讨JNK在ASD发病机制中的作用。方法选择2016年6月至2017年6月于湖南省儿童医院确诊的30例ASD患儿作为ASD组,另选择30例健康儿童作为对照组。检测外周血单核淋巴细胞(PBMC)中总JNK(T-JNK)及磷酸化JNK(p-JNK)表达水平;采用儿童期孤独症评定量表(CARS)评定疾病严重程度,并对JNK活化水平与CARS评分进行相关性分析。利用基因重组腺体病毒载体转染原代神经元细胞,根据干预措施不同分为JNK过表达组和对照组,检测两组中总JNK、磷酸化的JNK/ATF-2/c-Jun、囊泡谷氨酸转运体(VGLUT)和囊泡型GABA转运体(VGAT)表达水平。结果 ASD组和对照组PBMC中T-JNK表达水平差异无统计学意义(P 0. 05),但ASD组p-JNK表达水平以及p-JNK/T-JNK比值显著高于对照组(P 0. 05)。采用单因素回归分析评估外周血p-JNK/T-JNK比值与CARS评分相关性,结果显示JNK活化程度与疾病严重程度不具有相关性(r=0. 03,P 0. 05)。腺病毒载体转染原代神经元细胞后,JNK过表达组中T-JNK、p-NK/ATF-2/c-Jun表达水平均显著高于对照组(P 0. 05); JNK过表达组中VGAT的表达水平均显著低于对照组(P 0. 05),VGLUT的表达水平与对照组比无明显差异(P 0. 05)。结论 JNK信号通路可能参与了ASD的发病,但与疾病严重程度无关。上调JNK表达水平能使转录因子ATF-2和c-Jun活化,下调突触囊泡转运体中VGAT表达。  相似文献   

17.
The clinical and neuropathological findings of spinal muscular atrophy (SMA) in Holstein-Friesian calves are described in four females and one male from a dairy farm composed of 150 cows and 2 breeding bulls. Locomotion difficulties started at the age of 15 days, and progressed to paraparesis and tetraparesis in 2 weeks. Signs consistent with denervation were revealed with electromyography. The neuropathological examination showed degeneration and loss of motor neurons in the spinal cord, together with astrocytosis. Among the remaining motor neurons were ghost cells and neurons filled with accumulations of straight filaments measuring 10–12 nm in diameter, which were strongly immunoreactive with antibodies produced against phosphorylated neurofilaments. Degenerating cells in SMA did not stain with the method of in situ labelling of nuclear DNA fragmentation and did not show c-Jun immunoreactivity. This feature contrasts with the in situ labelling of DNA breaks of apoptotic cells and with the strong c-Jun immunoreactivity restricted to dying cells during the whole process of naturally occurring cell death in the developing central nervous system. These features suggest that cell death in SMA differs from programmed cell death during normal development, and that pathological cell death in SMA should not be considered as a mere persistence or reactivation of normally occurring developmental cell death. Received: 21 July 1996 / Revised, accepted: 11 August 1996  相似文献   

18.
The mating-induced preovulatory surge of luteinizing hormone (LH) lasts for at least 12 h in the female ferret. This prolonged increase in circulating LH is presumably accompanied by a corresponding elevation in the activity and output of luteinizing hormone-releasing hormone (LHRH) neurons projecting to the hypothalamic-hypophyseal portal blood vessels and adenohypophysis. We used the protein products of the immediate early genes (IEGs) c-fos, and c-jun as markers of neural activation in order to determine whether a sub-population of LHRH neurons is differentially activated by mating and whether non-LHRH neurons in specific forebrain regions are selectively activated at different times during the mating-induced preovulatory LH surge. In Experiment 1, estrous female ferrets were perfused 0.5, 1.5, 3.0, 6.0 or 12.0 h after receiving one 5-min intromission from a male or after being placed alone in a testing cage for 20 min. Fos-like immunoreactivity (Fos-IR; Oncogene Ab-2 antiserum) and LHRH-like immunoreactivity (LHRH-IR; LR-1 antiserum) were visualized. The percentage of Fos-IR LHRH neurons was significantly augmented 1.5 h after mating but had returned to basal levels by 3.0 h. The double-labeled LHRH neurons were concentrated in the caudal medio-basal hypothalamus. In non-LHRH neurons the number of Fos-IR neural nuclei was significantly increased by mating in the medial preoptic area (MPOA), bed nucleus of the stria terminalis (BNST), medial amygdala (MA), ventrolateral hypothalamus (VLH), and midbrain central tegmental field (CTF) 1.5 h after mating but, as in LHRH neurons, had returned to basal levels by 3.0 h. In Experiment 2, estrous females were perfused 1.5 h or 8.0 h after either receiving one 5-min intromission or being placed alone in a testing cage, and the brains were processed for LHRH and c-Fos-like (DCH-1, Dr Gerard Evan), c-Jun-like (Jun-IR; Oncogene Ab-2) or Egr-1-like (Egr-IR; Santa Cruz) immunoreactivity. The percentage of LHRH neurons colabeled with both Fos-IR and Jun-IR was significantly greater in the 1.5 h group than in the unpaired group. Again, the induction of these IEG products occurred in LHRH neurons in the caudal medio-basal hypothalamus. Mating significantly increased the number of Fos-IR non-LHRH neural nuclei in the MPOA, BNST, MA, VMH and CTF, as well as the number of Egr-IR nuclei in the MPOA, BNST and MA in the 1.5 h group. By contrast, the number of Jun-IR non-LHRH neurons was unaffected by mating. In these Experiments we have identified a sub-population of LHRH neurons which, using Fos and Jun as markers of neural activation, is activated by mating and may be differentially involved in the generation of the preovulatory LH surge. Although the LHRH system is presumably activated throughout the duration of the 12 h preovulatory LH surge, c-Fos and c-Jun immunoreactivity in LHRH neurons is augmented only transiently. Fos-IR and Egr-IR in non-LHRH neurons show a similar time-course. Together, these results suggest that the presence of augmented levels of these proteins is not required for the maintenance or termination of the preovulatory output of LHRH.  相似文献   

19.
目的 检测孤独症谱系障碍(ASD)患儿的c-Jun氨基末端激酶(JNK)通路蛋白表达情况,探讨JNK在ASD发病机制中的作用。方法 选择2016年6月至2017年6月于湖南省儿童医院确诊的30例ASD患儿作为ASD组,另选择30例健康儿童作为对照组。检测外周血单核淋巴细胞(PBMC)中总JNK(T-JNK)及磷酸化JNK(p-JNK)表达水平;采用儿童期孤独症评定量表(CARS)评定疾病严重程度,并对JNK活化水平与CARS评分进行相关性分析。利用基因重组腺体病毒载体转染原代神经元细胞,根据干预措施不同分为JNK过表达组和对照组,检测两组中总JNK、磷酸化的JNK/ATF-2/c-Jun、囊泡谷氨酸转运体(VGLUT)和囊泡型GABA转运体(VGAT)表达水平。结果 ASD组和对照组PBMC中T-JNK表达水平差异无统计学意义(P>0.05),但ASD组p-JNK表达水平以及p-JNK/T-JNK比值显著高于对照组(P<0.05)。采用单因素回归分析评估外周血p-JNK/T-JNK比值与CARS评分相关性,结果显示JNK活化程度与疾病严重程度不具有相关性(r=0.03,P>0.05)。腺病毒载体转染原代神经元细胞后,JNK过表达组中T-JNK、p-NK/ATF-2/c-Jun表达水平均显著高于对照组(P<0.05);JNK过表达组中VGAT的表达水平均显著低于对照组(P<0.05),VGLUT的表达水平与对照组比无明显差异(P>0.05)。结论 JNK信号通路可能参与了ASD的发病,但与疾病严重程度无关。上调JNK表达水平能使转录因子ATF-2和c-Jun活化,下调突触囊泡转运体中VGAT表达。  相似文献   

20.
3-硝基丙酸多次化学预处理对多巴胺能神经元的保护作用   总被引:2,自引:0,他引:2  
目的探讨3-硝基丙酸(3-NP)多次化学预处理对多巴胺能神经元的保护作用及可能机制。方法应用MPTP(30mg/kg)在C57BL小鼠上复制帕金森病模型,以3-NP(20mg/kg)行预处理,检测小鼠中脑黑质凋亡率和转录因子c-Jun的阳性细胞数量及c-Jun的蛋白水平;应用MPP^+(0.25mmol/L)在SH—SY5Y细胞制作帕金森病模型,以3-NP(0.2mmol/L)进行预处理,并将携带显性突变体c—JuncDNA片段的真核表达载体质粒pcDNA3(HA)-Jun—dn转染SH—SY5Y细胞,检测各组细胞的c-Jun表达水平及凋亡率。结果小鼠中脑黑质凋亡率:MPTP组较对照组明显升高(P〈0.01),3-NP单次、多次预处理后均明显降低(P〈0.05,P〈0.01);c—Jun阳性细胞数:MPTP组较对照组明显增加(P〈0.05),3-NP单次预处理组与MPTP组比较无明显差异,3-NP多次预处理后明显降低(P〈0.05);c—Jun蛋白水平:与其阳性细胞数变化一致;细胞凋亡率:MPP^+组较对照组明显升高,3-NP单次、多次预处理组细胞凋亡率明显降低(P〈0.05,P〈0.01);c-Jun蛋白水平变化与中脑黑质一致;经pcDNA3(HA)-Jundn转染的细胞,其c-Jun的表达较未转染细胞明显降低(P〈0.01),其凋亡率也下降(P〈0.01)。结论3-NP单次、多次预处理对多巴胺能神经元确有保护作用,多次预处理保护效果更强,其机制与抑制转录因子c-Jun的表达,降低其蛋白水平有关。  相似文献   

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