丰富环境对缺血性脑卒中小鼠海马区Bcl-2和Bax蛋白表达和认知功能的效果

doi:10.3969/j.issn.1006-9771.2020.05.009

《中国康复理论与实践》 ›› 2020, Vol. 26 ›› Issue (5): 539-543.doi: 10.3969/j.issn.1006-9771.2020.05.009

丰富环境对缺血性脑卒中小鼠海马区Bcl-2和Bax蛋白表达和认知功能的效果

王传杰¹,吴毅²(),陶峰¹,杨雷¹

1.复旦大学附属金山医院康复科,上海市 201508
2.复旦大学附属华山医院康复科,上海市 200040

收稿日期:2019-07-14 修回日期:2019-09-18 出版日期:2020-05-25 发布日期:2020-05-29
通讯作者: 吴毅 E-mail:wuyi@fudan.edu.cn
作者简介:王传杰(1982-),男,汉族,山东招远市人,博士,主治医师,主要研究方向：脑卒中康复。
基金资助:
1.国家自然科学基金项目(81672242);2.上海市卫计委重要薄弱学科建设项目(2015ZB0401)

Effects of Enriched Environment on Cognition and Expression of Bcl-2/Bax Protein in Hippocampus after Ischemic Stroke in Mice

WANG Chuan-jie¹,WU Yi²(),TAO Feng¹,YANG Lei¹

1. Department of Rehabilitation, Jinshan Hospital Affiliated to Fudan University, Shanghai 201508, China
2. Department of Rehabilitation, Huashan Hospital Affiliated to Fudan University, Shanghai 200040, China

Received:2019-07-14 Revised:2019-09-18 Published:2020-05-25 Online:2020-05-29
Contact: WU Yi E-mail:wuyi@fudan.edu.cn
Supported by:
National Natural Science Foundation of China(81672242);Shanghai Health and Family Planning Committee Key Construction Projects on Weak Discipline(2015ZB0401)

摘要/Abstract

摘要：

目的探讨丰富环境干预对缺血性脑卒中小鼠空间学习记忆能力,以及海马区凋亡相关蛋白Bcl-2和Bax表达的影响。方法清洁级成年雄性C57BL/6小鼠42只,接受永久性左侧大脑中动脉栓塞术。术后3 d,将造模成功的小鼠32只随机分为标准饲养组(n = 16)和丰富环境组(n = 16)。另选8只小鼠为假手术组。假手术组和标准饲养组置于标准环境中饲养,丰富环境组置于丰富环境中饲养。21 d后,行Morris水迷宫测试,Western blotting和免疫荧光染色检测海马区Bcl-2和Bax蛋白水平。结果与标准饲养组相比,丰富环境组逃避潜伏期缩短(P < 0.05),目标象限内停留时间、停留距离和穿过原有平台次数增加( P < 0.05); Bcl-2水平升高( P < 0.05),Bax水平降低( P < 0.05)。结论丰富环境可以改善缺血性脑卒中小鼠空间学习和记忆功能,可能与抵制海马区细胞凋亡有关。

关键词: 缺血性脑卒中, 丰富环境, 认知, 凋亡, 小鼠

Abstract:

Objective To explore the effect of enriched environment on spatial learning and memory of mice after ischemic stroke and the expression of apoptotic regulatory protein Bcl-2 and Bax in hippocampus.Methods Clean grade adult male C57BL/6 mice (n = 42) were occluded left middle cerebral artery permanently. Three days after operation, the modeling mice were randomly divided into standard group (n = 16) and enriched environment group (n = 16). Other eight mice were as sham group. The sham group and the standard group were fed in standard environment, while the enriched group was fed in enriched environment. They were tested with Morris Water Maze 21 days after intervention, and the expression of Bcl-2 and Bax protein in hippocampus was detected with Western blotting and immunofluorescence staining.Results The latency was less in the enriched group than in the standard group (P < 0.05), and the time and swimming distance staying in the target quadrant were more ( P < 0.05), as well as the times crossing the target quadrant ( P < 0.05). Compared with the standard group, the expression of Bcl-2 increased in the enriched group, while the expression of Bax decreased ( P < 0.05). Conclusion Enriched environment can improve the spatial learning and memory of mice after ischemic stroke, which may be associated with reducing apoptosis in hippocampus.

Key words: ischemic stroke, enriched environment, cognition, apoptosis, mice

中图分类号:

R743.32

王传杰,吴毅,陶峰,杨雷. 丰富环境对缺血性脑卒中小鼠海马区Bcl-2和Bax蛋白表达和认知功能的效果[J]. 《中国康复理论与实践》, 2020, 26(5): 539-543.

WANG Chuan-jie,WU Yi,TAO Feng,YANG Lei. Effects of Enriched Environment on Cognition and Expression of Bcl-2/Bax Protein in Hippocampus after Ischemic Stroke in Mice[J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2020, 26(5): 539-543.

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参考文献 35

[1]	Xie H, Yu K, Zhou N, et al. Enriched environment elicits proangiogenic mechanisms after focal cerebral ischemia[J]. Transl Stroke Res, 2019, 10(2):150-159. doi: 10.1007/s12975-018-0629-8
[2]	dela Pena I C, Yoo A, Tajiri N, et al. Granulocyte colony-stimulating factor attenuates delayed tPA-induced hemorrhagic transformation in ischemic stroke rats by enhancing angiogenesis and vasculogenesis[J]. J Cereb Blood Flow Metab, 2015, 35(2):338-346. doi: 10.1038/jcbfm.2014.208
[3]	Ishiguro M, Kawasaki K, Suzuki Y, et al. A Rho kinase (ROCK) inhibitor, fasudil, prevents matrix metalloproteinase-9-related hemorrhagic transformation in mice treated with tissue plasminogen activator[J]. Neuroscience, 2012, 220(2):302-312. doi: 10.1016/j.neuroscience.2012.06.015
[4]	Stroes E S, Nierman M C, Meulenberg J J, et al. Intramuscular administration of AAV1-lipoprotein lipase S447X lowers triglycerides in lipoprotein lipase-deficient patients[J]. Arterioscler Thromb Vasc Biol, 2008, 28(12):2303-2304. doi: 10.1161/ATVBAHA.108.175620
[5]	Gaudet D, de Wal J, Tremblay K, et al. Review of the clinical development of alipogene tiparvovec gene therapy for lipoprotein lipase deficiency[J]. Atheroscler Suppl, 2010, 11(1):55-60.
[6]	Martino A T, Basner-Tschakarjan E, Markusic D M, et al. Engineered AAV vector minimizes in vivo targeting of transduced hepatocytes by capsid-specific CD₈^± T cells[J]. Blood, 2013, 121(12):2224-2233. doi: 10.1182/blood-2012-10-460733 pmid: 23325831
[7]	Benowitz L I, Carmichael S T. Promoting axonal rewiring to improve outcome after stroke[J]. Neurobiol Dis, 2010, 37(2):259-266. doi: 10.1016/j.nbd.2009.11.009 pmid: 19931616
[8]	Sakalem M E, Seidenbecher T, Zhang M, et al. Environmental enrichment and physical exercise revert behavioral and electrophysiological impairments caused by reduced adult neurogenesis[J]. Hippocampus, 2017, 27(1):36-51. doi: 10.1002/hipo.22669 pmid: 27701786
[9]	Floros K V, Thomadaki H, Florou D, et al. Alterations in mRNA expression of apoptosis-related genes BCL2, BAX, FAS, caspase-3, and the novel member BCL2L12 after treatment of human leukemic cell line HL60 with the antineoplastic agent etoposide[J]. Ann N Y Acad Sci, 2006, 10(90):89-97.
[10]	Ohline S M, Abraham W C. Environmental enrichment effects on synaptic and cellular physiology of hippocampal neurons[J]. Neuropharmacology, 2018, 31(3):254-261.
[11]	Doyle K P, Buckwalter M S. A mouse model of permanent focal ischemia: distal middle cerebral artery occlusion[J]. Methods Mol Biol, 2014, 11(35):103-110.
[12]	Vorhees C V, Williams M T. Morris water maze: procedures for assessing spatial and related forms of learning and memory[J]. Nat Protoc, 2006, 1(2):848-858. doi: 10.1038/nprot.2006.116
[13]	Zhang Q, Wu Y, Sha H, et al. Early exercise affects mitochondrial transcription factors expression after cerebral ischemia in rats[J]. Int J Mol Sci, 2012, 13(2):1670-1679. doi: 10.3390/ijms13021670 pmid: 22408416
[14]	Chen C, Lin X, Wang J, et al. Effect of HMGB1 on the paracrine action of EPC promotes post-ischemic neovascularization in mice[J]. Stem Cells, 2014, 32(10):2679-2689. doi: 10.1002/stem.1754
[15]	Tsai C F, Thomas B, Sudlow C L. Epidemiology of stroke and its subtypes in Chinese vs white populations: a systematic review[J]. Neurology, 2013, 81(3):264-272. doi: 10.1212/WNL.0b013e31829bfde3
[16]	Wong A, Mok V. Stroke: Poststroke cognitive impairment-what are we measuring?[J]. Nat Rev Neurol, 2015, 11(9):487-488. doi: 10.1038/nrneurol.2015.130
[17]	Brown J, Cooper-Kuhn C M, Kempermann G, et al. Enriched environment and physical activity stimulate hippocampal but not olfactory bulb neurogenesis[J]. Eur J Neurosci, 2003, 17(10):2042-2046. doi: 10.1046/j.1460-9568.2003.02647.x
[18]	Mustroph M L, Chen S, Desai S C, et al. Aerobic exercise is the critical variable in an enriched environment that increases hippocampal neurogenesis and water maze learning in male C57BL/6J mice[J]. Neuroscience, 2012, 219(9):62-71. doi: 10.1016/j.neuroscience.2012.06.007
[19]	Kempermann G, Kuhn H G, Gage F H. Experience-induced neurogenesis in the senescent dentate gyrus[J]. J Neurosci, 1998, 18(9):3206-3212. pmid: 9547229
[20]	Birch A M, McGarry MN B, Kelly A M. Short-term environmental enrichment, in the absence of exercise, improves memory, and increases NGF concentration, early neuronal survival, and synaptogenesis in the dentate gyms in a time-dependent manner[J]. Hippocampus, 2013, 23(6):437-450. doi: 10.1002/hipo.22103 pmid: 23460346
[21]	Griñan-Ferré C, Pérez-Cáceres D, Gutiérrez-Zetina S M, et al. Environmental enrichment improves behavior, ognition, and brain functional markers in young senescence-accelerated prone mice (SAMP8)[J]. Mol Neurobiol, 2016, 53(4):2435-2450. doi: 10.1007/s12035-015-9210-6 pmid: 26014386
[22]	Monteiro B M, Moreira F A, Massensini A R, et al. Enriched environment increases neurogenesis and improves social memory persistence in socially isolated adult mice[J]. Hippocampus, 2014, 24(2):239-248. pmid: 24123782
[23]	Leggio M G, Mandolesi L, Federico F, et al. Environmental enrichment promotes improved spatial abilities and enhanced dendritic growth in the rat[J]. Behav Brain Res, 2005, 163(1):78-90. doi: 10.1016/j.bbr.2005.04.009
[24]	He S, Ma J, Liu N, et al. Early enriched environment promotes neonatal GABAergic neurotransmission and accelerates synapse maturation[J]. J Neurosci, 2010, 30(23):7910-7916. doi: 10.1523/JNEUROSCI.6375-09.2010
[25]	Zhang X, Chen X P, Lin J B, et al. Effect of enriched environment on angiogenesis and neurological functions in rats with focal cerebral ischemia[J]. Brain Res, 2017, 165(9):176-185.
[26]	Yuan J. Neuroprotective strategies targeting apoptotic and necrotic cell death for stroke[J]. Apoptosis, 2009, 14(4):469-477. doi: 10.1007/s10495-008-0304-8
[27]	Kristiansen M, Ham J. Programmed cell death during neuronal development: the sympathetic neuron model[J]. Cell Death Differ, 2014, 21(4):1025-1035. doi: 10.1038/cdd.2014.47
[28]	Subbarayan S, Subramanian S, Senthil Kumar N. Recombinant pierisin-5 induces apoptosis and differential expression of Bcl-2, Bax, and p53 in human cancer cells[J]. DNA Cell Biol, 2019, 38(8):773-785. doi: 10.1089/dna.2018.4520
[29]	Wu H, Medeiros L J, Young K H. Apoptosis signaling and BCL-2 pathways provide opportunities for novel targeted therapeutic strategies in hematologic malignances[J]. Blood Rev, 2018, 32(1):8-28. doi: 10.1016/j.blre.2017.08.004
[30]	Seo T B, Kim T W, Shin M S, et al. Aerobic exercise alleviates ischemia-induced memory impairment by enhancing cell proliferation and suppressing neuronal apoptosis in hippocampus[J]. Int Neurourol J, 2014, 18(4):187-197. doi: 10.5213/inj.2014.18.4.187
[31]	Li M, Peng J, Wang M D, et al. Passive movement improves the learning and memory function of rats with cerebral infarction by inhibiting neuron cell apoptosis[J]. Mol Neurobiol, 2014, 49(1):216-221. doi: 10.1007/s12035-013-8512-9
[32]	Aboutaleb N, Shamsaei N, Khaksari M, et al. Pre-ischemic exercise reduces apoptosis in hippocampal CA3 cells after cerebral ischemia by modulation of the Bax/Bcl-2 proteins ratio and prevention of caspase-3 activation[J]. J Physiol Sci, 2015, 65(5):435-443. doi: 10.1007/s12576-015-0382-7 pmid: 26012958
[33]	Meng Z, Liu T, Song Y, et al. Exposure to an enriched environment promotes the terminal maturation and proliferation of natural killer cells in mice[J]. Brain Behav Immun, 2019, 77(5):150-160. doi: 10.1016/j.bbi.2018.12.017
[34]	Chen X, Zhang X, Xue L, et al. Treatment with enriched environment reduces neuronal apoptosis in the periinfarct cortex after cerebral ischemia/reperfusion injury[J]. Cell Physiol Biochem, 2017, 41(4):1445-1456. doi: 10.1159/000468368
[35]	Xie M, Yi C, Luo X, et al. Glial gap junctional communication involvement in hippocampal damage after middle cerebral artery occlusion[J]. Ann Neurol, 2011, 70(1):121-132. doi: 10.1002/ana.22386

组别	n	第1天	第2天	第3天	第4天	第5天	F值	P值
假手术组	8	63.8±16.5	51.9±13.8	43.3±12.5	30.3±13.8	20.6±9.2	17.328	< 0.001
标准饲养组	8	62.4±13.3	56.2±16.8^a	52.7±14.8^a	46.9±12.6^a	40.4±10.8^a	4.765	0.013
丰富环境组	8	60.2±11.8	53.5±10.9^b	46.5±15.6^b	32.1±9.8^b	22.9±7.3^b	15.863	< 0.001
F值		0.308	3.343	6.342	10.239	11.298
P值		0.792	0.028	0.011	< 0.001	< 0.001

组别	n	游动距离(m)	游动时间(s)	穿过原平台次数
假手术组	8	6.3±2.5	21.9±3.6	3.9±0.5
标准饲养组	8	2.4±1.3^a	8.4±2.9^a	1.2±0.6^a
丰富环境组	8	5.8±1.8^b	19.5±2.3^b	3.5±0.3^b
F值		12.728	13.146	7.932
P值		< 0.001	< 0.001	0.002

组别	n	Bcl-2	Bax	Bcl-2/Bax
假手术组	8	0.893±0.125	0.497±0.145	1.753±0.138
标准饲养组	8	0.497±0.139^a	0.804±0.119^a	0.671±0.163^a
丰富环境组	8	0.943±0.128^b	0.625±0.133^b	1.435±0.103^b
F值		13.384	12.751	15.654
P值		< 0.001	< 0.001	< 0.001

组别	n	Bcl-2	Bax	Bcl-2/Bax
假手术组	8	10976.8±0.125	4064.7±527.5	2.644±0.168
标准饲养组	8	4896.9±0.139^a	8065.8±709.9^a	0.609±0.119^a
丰富环境组	8	9825.3±886.1^b	5389.5±587.3^b	1.805±0.171^b
F值		17.769	14.264	19.096
P值		< 0.001	< 0.001	< 0.001

丰富环境对缺血性脑卒中小鼠海马区Bcl-2和Bax蛋白表达和认知功能的效果

Effects of Enriched Environment on Cognition and Expression of Bcl-2/Bax Protein in Hippocampus after Ischemic Stroke in Mice

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