丰富环境对缺血缺氧脑损伤新生大鼠海马脑源性神经营养因子表达及细胞凋亡的影响
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摘要
目的:探讨丰富环境对缺血缺氧脑损伤(HIBD)新生大鼠海马脑源性神经营养因子(BDNF)表达及细胞凋亡的影响。方法:采用随机数字表法将36只7日龄新生大鼠分为假手术组、模型组及丰富环境组,各组又分为术后7d、28d两个亚组(n=6)。采用Rice-Vannucci经典方法建立新生大鼠HIBD模型。模型组及假手术组不予任何干预,丰富环境组予以早期抚触及丰富环境刺激治疗。术后7d、28d采用水迷宫检测方法评估大鼠学习记忆能力,免疫组化法检测大鼠海马CA1区BDNF的表达,TUNEL法检测海马CA1区细胞凋亡。结果:术后7d、28d,与模型组比较,丰富环境组逃避潜伏期均缩短(P<0.05),穿越平台次数增多(P<0.05),BDNF表达升高(P<0.05),TUNEL阳性细胞数降低(P<0.05)。结论:丰富环境能改善HIBD新生大鼠学习记忆能力,其机制可能与上调海马区BDNF的表达及抑制细胞凋亡有关。
Objective:To investigate the effect of enriched environment intervention on brain-derived neurotrophic factor expression and apoptosis in hippocampus of hypoxic-ischemic brain damaged(HIBO) neonatal rats.Method:Thirty-six male 7-day-old rats were randomly divided into sham operation group, model group, enriched environment group, each group was further divided into 7 days and 28 days subgroups(n=6). HIBD model of neonatal rats was established according to Rice-Vannucci classical methods. The model group and the sham operation group accepted no treatment. Enriched enriched environment group was treated with early touch and enriched environment stimulation. 7 days and 28 days after operation, the learning and memory ability was evaluated with the water maze detection method, the expression levels of BDNF were detected by immunohistochemical method. The apoptosis was detected by TUNEL method.Result:Compared with the model group, the hidden platform escape latency period(EL) was significantly shortened(P<0.05) in enriched environment group 7 days and 28 days after operation, the cross-platform number within 2 minutes was significantly increased(P<0.05),the expression of BDNF increased(P<0.05),TUNEL positive cell number decreased(P<0.05).Conclusion:Enriched environment can improve the learning and memory ability in hypoxic-ischemic brain damage neonatal rat, which may be related to the up regulation of BDNF expression and anti-apoptosis in hippocampus.
Objective:To investigate the effect of enriched environment intervention on brain-derived neurotrophic factor expression and apoptosis in hippocampus of hypoxic-ischemic brain damaged(HIBO) neonatal rats.Method:Thirty-six male 7-day-old rats were randomly divided into sham operation group, model group, enriched environment group, each group was further divided into 7 days and 28 days subgroups(n=6). HIBD model of neonatal rats was established according to Rice-Vannucci classical methods. The model group and the sham operation group accepted no treatment. Enriched enriched environment group was treated with early touch and enriched environment stimulation. 7 days and 28 days after operation, the learning and memory ability was evaluated with the water maze detection method, the expression levels of BDNF were detected by immunohistochemical method. The apoptosis was detected by TUNEL method.Result:Compared with the model group, the hidden platform escape latency period(EL) was significantly shortened(P<0.05) in enriched environment group 7 days and 28 days after operation, the cross-platform number within 2 minutes was significantly increased(P<0.05),the expression of BDNF increased(P<0.05),TUNEL positive cell number decreased(P<0.05).Conclusion:Enriched environment can improve the learning and memory ability in hypoxic-ischemic brain damage neonatal rat, which may be related to the up regulation of BDNF expression and anti-apoptosis in hippocampus.
引文
[1]娄玉霞.单唾液酸神经节苷脂注射液在新生儿缺氧缺血性脑病治疗中的临床价值[J].现代预防医学,2014,41(4):635—636.
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[16]刘传军,郭延奎,李亚鲁,等.早期干预对缺氧缺血脑损伤新生鼠大脑皮质突触重塑的影响[J].中国妇幼保健,2011,26(11):1702—1704.
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[19]陈光福,张蕴芳,龙琦,等.丰富环境干预促进缺氧缺血性脑损伤新生大鼠神经元细胞增殖和功能修复[J].中国当代儿科杂志,2012,14(2):139—143.
[20]于若谷,赵聪敏,王丽雁,等.丰富环境干预后HIBD大鼠脑超微结构改变[J].第三军医大学学报,2006,28(8):819—820.
[21]Xu X,Ye L,Ruan Q.Environmental enrichment induces synaptic structural modification after transient focal cerebral ischemia in rats[J].Exp Biol Med(Maywood),2009,234(3):296—305.
[22]Ma H,Yu B,Kong L,et al.Neural stem cells over-expressing brain-derived neurotrophic factor(BDNF)stimulate synaptic protein expression and promote functional recovery following transplantation in rat model of traumatic brain injury[J].Neurochem Res,2012,37(1):69—83.
[23]Pan M,Li Z,Yeung V,et al.Dietary supplementation of soy germ phytoestrogens or estradiol improves spatial memory performance and increases gene expression of BDNF,Trk B receptor and synaptic factors in ovariectomized rats[J].Nutr Metab(Lond),2010,(7):75.
[24]Kim HJ,Lee JH,Kim SH.Therapeutic effects of human mesenchymal stem cells on traumatic brain injury in rats:secretion of neurotrophic factors and inhibition of apoptosis[J].J Neurotrauma,2010,27(1):131—138.
[25]江东,于建云.脑源性神经营养因子临床研究进展[J].神经解剖学杂志,2011,27(2):221—225.
[26]胡泳菊,汤永红.脑源性神经营养因子对神经干细胞增殖分化的影响[J].现代医药卫生,2014,30(1):53—55.
[27]张国庆.丰富环境干预对新生大鼠的神经康复作用及其机制的研究[D].上海:复旦大学,2007.
[28]张勤丽,牛侨.细胞凋亡机制概述[J].环境与职业医学,2007,24(1):102—107.
[29]俞丹.外源性BDNF在宫内缺氧环境中对胎盘及胚鼠血脑屏障通透性和脑细胞凋亡的作用及信号传导的研究[D].成都:四川大学,2004.
[30]宋名杨,朱路文,叶涛,等.丰富环境促进缺血缺氧性脑损伤修复的研究进展[J].中国康复理论与实践,2016,22(1):61—64.
[2]邵粉丽.早期干预对缺氧缺血性脑病新生儿神经行为发育的影响[J].吉林医学,2012,33(30):6519.
[3]吴桂华,邵银进,曾圆霞.早期干预对中重度新生儿缺氧缺血性脑病预后的影响[J].赣南医学院学报,2013,33(4):523—525.
[4]Seo JH,Yu JH,Suh H,et al.Fibroblast growth factor-2 induced by enriched environment enhances angiogenesis and motor function in chronic hypoxic-ischemic brain injury[J].PLo S One,2013,8(9):e74405.
[5]Morgan C,Novak I,Badawi N.Enriched environments and motor outcomes in cerebral palsy:systematic review and meta-analysis[J].Pediatrics,2013,132(3):e735—746.
[6]Rojas JJ,Deniz BF,Miguel PM,et al.Effects of daily environmental enrichment on behavior and dendritic spine density in hippocampus following neonatal hypoxia-ischemia in the rat[J].Exp Neurol,2013,(241):25—33.
[7]付美红,李海涛.脑源性神经营养因子与脑缺血的研究进展[J].安徽医药,2012,16(6):717—720.
[8]Young D,Lawlor PA,Leone P,et al.Environmental enrichment inhibits spontaneous apoptosis,prevents seizures and is neuroprotective[J].Nat Med,1999,5(4):448—453.
[9]Rice JE 3rd,Vannucci RC,Brierley JB.The influence of immaturity on hypoxic-ischemic brain damage in the rat[J].Ann Neurol,1981,9(2):131—141.
[10]AndinéP,Thordstein M,Kjellmer I,et al.Evaluation of brain damage in a rat model of neonatal hypoxic-ischemia[J].J Neurosci Methods,1990,35(3):253—260.
[11]Nithianantharajah J,Hannan AJ.Enriched environments,experience-dependent plasticity and disorders of the nervous system[J].Nat Rev Neurosci,2006,7(9):697—709.
[12]Morris RGM.Spatial localization does not require the presence of local cues[J].Learning&Motivation,1981,12(2):239—260.
[13]诸葛启钏.大鼠脑立体定位图谱[M].北京:人民卫生出版社,2005.104.
[14]李娴,谢斌.丰富环境与脑卒中康复[J].中国康复理论与实践,2012,18(1):47—52.
[15]Hosseiny S,Pietri M,Petit-Paitel A,et al.Differential neuronal plasticity in mouse hippocampus associated with various periods of enriched environment during postnatal development[J].Brain Struct Funct,2015,220(6):3435—3448.
[16]刘传军,郭延奎,李亚鲁,等.早期干预对缺氧缺血脑损伤新生鼠大脑皮质突触重塑的影响[J].中国妇幼保健,2011,26(11):1702—1704.
[17]Balduini W,Carloni S,Perrone S,et al.The use of melatonin in hypoxic-ischemic brain damage:an experimental study[J].J Matern Fetal Neonatal Med,2012,25(Suppl 1):119—124.
[18]辛庆刚,张丽华,张士岭.早期干预对HIBD大鼠神经干细胞分化的影响[J].中国伤残医学,2013,21(7):97—99.
[19]陈光福,张蕴芳,龙琦,等.丰富环境干预促进缺氧缺血性脑损伤新生大鼠神经元细胞增殖和功能修复[J].中国当代儿科杂志,2012,14(2):139—143.
[20]于若谷,赵聪敏,王丽雁,等.丰富环境干预后HIBD大鼠脑超微结构改变[J].第三军医大学学报,2006,28(8):819—820.
[21]Xu X,Ye L,Ruan Q.Environmental enrichment induces synaptic structural modification after transient focal cerebral ischemia in rats[J].Exp Biol Med(Maywood),2009,234(3):296—305.
[22]Ma H,Yu B,Kong L,et al.Neural stem cells over-expressing brain-derived neurotrophic factor(BDNF)stimulate synaptic protein expression and promote functional recovery following transplantation in rat model of traumatic brain injury[J].Neurochem Res,2012,37(1):69—83.
[23]Pan M,Li Z,Yeung V,et al.Dietary supplementation of soy germ phytoestrogens or estradiol improves spatial memory performance and increases gene expression of BDNF,Trk B receptor and synaptic factors in ovariectomized rats[J].Nutr Metab(Lond),2010,(7):75.
[24]Kim HJ,Lee JH,Kim SH.Therapeutic effects of human mesenchymal stem cells on traumatic brain injury in rats:secretion of neurotrophic factors and inhibition of apoptosis[J].J Neurotrauma,2010,27(1):131—138.
[25]江东,于建云.脑源性神经营养因子临床研究进展[J].神经解剖学杂志,2011,27(2):221—225.
[26]胡泳菊,汤永红.脑源性神经营养因子对神经干细胞增殖分化的影响[J].现代医药卫生,2014,30(1):53—55.
[27]张国庆.丰富环境干预对新生大鼠的神经康复作用及其机制的研究[D].上海:复旦大学,2007.
[28]张勤丽,牛侨.细胞凋亡机制概述[J].环境与职业医学,2007,24(1):102—107.
[29]俞丹.外源性BDNF在宫内缺氧环境中对胎盘及胚鼠血脑屏障通透性和脑细胞凋亡的作用及信号传导的研究[D].成都:四川大学,2004.
[30]宋名杨,朱路文,叶涛,等.丰富环境促进缺血缺氧性脑损伤修复的研究进展[J].中国康复理论与实践,2016,22(1):61—64.