>
网站首页期刊介绍通知公告编 委 会投稿须知电子期刊广告合作联系我们
最新消息:
苯丙酮尿症大鼠海马神经元损伤及其与BDNF/TrkB通路的关系
作者:吕书博  张展  赵德华  李晓乐  苏立  罗春伟  孟云  王丽雯 
单位:郑州大学第三附属医院 新生儿筛查中心, 河南 郑州 450000
关键词:苯丙酮尿症 大鼠 海马 神经元 脑源性生长因子 酪氨酸激酶受体B 
分类号:R-33;R742.8
出版年·卷·期(页码):2019·38·第三期(461-466)
摘要:

目的:观察苯丙酮尿症大鼠海马神经元损伤及其与脑源性生长因子(BDNF)/酪氨酸激酶受体B(TrkB)通路的关系。方法:将24只大鼠根据随机数字表法分为对照组和苯丙酮尿症组各12只。用10% FeCl3液显色进行尿液实验,采用高效液相色谱-荧光检测法测定大鼠大脑皮层及血清中酪氨酸和苯丙氨酸水平,HE染色观察海马CA1区病理变化,采用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记测定(TUNEL)法测定神经元凋亡情况,采用蛋白质印迹法测定海马含半胱氨酸的天冬氨酸蛋白水解酶3(Caspase-3)、B淋巴细胞瘤-2基因(Bcl-2)蛋白和BDNF、TrkB、磷酸化细胞外调节蛋白激酶(p-ERK)、磷酸化丝氨酸/苏氨酸激酶(P-Akt)蛋白含量。结果:苯丙酮尿症组尿液显色为强阳性;大脑皮层和血清苯丙氨酸水平明显高于对照组(P<0.05),大脑皮层和血清酪氨酸水平低于对照组(P<0.05);海马CA1区组织结构紊乱,细胞结构模糊、排列紊乱,见神经元细胞变性、坏死;海马CA1区细胞凋亡数高于对照组(P<0.05);海马Caspase-3、Bcl-2、BDNF、TrkB、p-ERK、P-Akt蛋白含量高于对照组(P<0.05)。结论:苯丙酮尿症大鼠海马神经元存在损伤,其机制可能与BDNF/TrkB通路有关。

Objective:To observe the relationship between hippocampal neuron injury in rats with phenylketonuria and the brain-derived growth factor(BDNF)/tyrosine kinase receptor B(TrkB) pathway, and to explore the possible mechanism of hippocampal neuron injury. Methods:Twenty-four rats were divided into control group and phenylketonuria group by random number method with 12 rats in each group. Urine test was conducted with 10%FeCl3 liquid chromogenic analysis. Tyrosine and phenylalanine levels in cerebral cortex and serum were determined by HPLC-fluorescence detection. Pathological changes in the CA1 region of the hippocampus were observed by HE staining. Levels of cysteine-containing aspartate proteolytic enzyme 3(Caspase-3), b-lymphocytoma-2(bcl-2), BDNF, TrkB, phosphorylated extracellular regulatory protein kinase(p-erk), and phosphorylated serine/threonine kinase(P-Akt) proteins in hippocampus were determined by Western blot. Results:The urine of rats in phenylketonuria group was strongly positive. The levels of phenylalanine in the cerebral cortex and serum in the phenylketonuria group were significantly higher than those of the control group(P<0.05), while the levels of phenylalanine in the cerebral cortex and serum in the phenylketonuria group were significantly lower than those of the control group(P<0.05). In phenylketonuria group, the tissue structure in CA1 area of the hippocampus was disordered, and the cell structure was fuzzy and disordered. The degeneration and necrosis of neurons were observed. The number of apoptic cells in the CA1 region of hippocampus in phenylketonuria group was higher than that of the control group(P<0.05). The levels of Caspase-3, Bcl-2, BDNF, TrkB, p-erk and p-akt protein in hippocampus of the phenylketonuria group were higher than those of the control group(P<0.05). Conclusion:The mechanism of hippocampal neurons injury in phenylketonuria rats may be related to the BDNF/TrkB pathway.

参考文献:

[1] DEON M,LANDGRAF S S,LAMBERTY J F,et al. Protective effect of L-carnitine on Phenylalanine-induced DNA damage[J].Metab Brain Dis,2015,30(4):925-933.
[2] HORLING K,SCHLEGEL G,SCHULZ S,et al. Hippocampal synaptic connectivity in phenylketonuria[J].Hum Mol Genet, 2015,24(4):1007-1018.
[3] MCCARTHY D M,MUELLER K A,CANNON E N,et al.Prenatal cocaine exposure alters bdnf-trkb signaling in the embryonic and adult brain[J].Dev Neurosci,2016,38(5):365-374.
[4] JANARDHANAN A,SADANAND A,VANISREE A J.Nardostachys jatamansi targets BDNF-TrkB to alleviate ketamine-induced schizophrenia-like symptoms in rats[J].Neuropsychobiology,2016,74(2):104-114.
[5] DOS REIS E A,RIEGER E,DE SOUZA S S,et al.Effects of a co-treatment with pyruvate and creatine on dendritic spines in rat hippocampus and posterodorsal medial amygdala in a phenylketonuria animal model[J].Metab Brain Dis,2013,28(3):509-517.
[6] 洪敏,唐爱国.苯丙酮尿症脑损害机制的研究进展[J].国外医学(生理、病理科学与临床分册),2004,24(5):459-462.
[7] 马瑞松,江洪,李元红,等.青蒿素抑制心肌缺血再灌注中的细胞凋亡[J].现代医学,2016,44(7):919-922.
[8] WU X,ZHANG L S,TOOMBS J,et al.Extra-mitochondrial prosurvival BCL-2 proteins regulate gene transcription by inhibiting the SUFU tumour suppressor[J].Nat Cell Biol,2017,19(10):1226-1236.
[9] 郑壮勋,郑成芳,陈壮荣.神经节苷脂辅助治疗老年急性脑梗死的临床疗效及对血清BDNF、NGF和炎症因子的影响[J].现代医学,2018,46(3):286-290.
[10] MYSONA B A,ZHAO J,BOLLINGER K E.Role of BDNF/TrkB pathway in the visual system:therapeutic implications for glaucoma[J].Expert Rev Ophthalmol,2017,12(1):69-81.
[11] ANDERSON E M,WISSMAN A M,CHEMPLANIKAL J,et al.BDNF-TrkB controls cocaine-induced dendritic spines in rodent nucleus accumbens dissociated from increases in addictive behaviors[J].Proc Natl Acad Sci U S A,2017,114(35):9469-9474.
[12] CHEN G,LIN X,LI G,et al.Risperidone reverses the spatial object recognition impairment and hippocampal BDNF-TrkB signalling system alterations induced by acute MK-801 treatment[J].Biomed Rep,2017,6(3):285-290.
[13] 吴晓东,姜树原,贾小娥,等.低氧对BDNF和TrkB受体及其信号通路影响的研究进展[J].动物医学进展,2018,39(8):101-105.
[14] GUO J Q,DENG H H,BO X,et al.Involvement of BDNF/TrkB and ERK/CREB axes in nitroglycerin-induced rat migraine and effects of estrogen on these signals in the migraine[J].Biol Open,2017,6(1):8-16.
[15] ZHONG J B,LI X,ZHONG S M,et al.Knockdown of long noncoding antisense RNA brain-derived neurotrophic factor attenuates hypoxia/reoxygenation-induced nerve cell apoptosis through the BDNF-TrkB-PI3K/Akt signaling pathway[J].Neuroreport,2017,28(14):910-916.

服务与反馈:
文章下载】【发表评论】【查看评论】【加入收藏
提示:您还未登录,请登录!点此登录
您是第 187076 位访问者


copyright ©《东南大学学报(医学版)》编辑部
联系电话:025-87232481 83272483
电子邮件:
bjb@pub.seu.edu.cn

苏ICP备09058364