缺氧诱导因子-1α、ICAM-1、γ-干扰素及BDNF在脑出血模型大鼠中的表达水平变化
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摘要
目的探讨缺氧诱导因子-1α(Hypoxia inducible factor-1α,HIF-1α)、细胞间黏附分子-1(Inter-cellular cell adhesion molecule-1,ICAM-1)、γ-干扰素(Interferon-γ,IFN-γ)及脑源性神经营养因子(Brain de-rived neurotrophic factor,BDNF)在脑出血模型大鼠中的表达水平变化。方法选取30只SD健康雄性大鼠,其中10只大鼠作为正常组,不做任何处理,另外20只大鼠建立脑出血模型,使用Morris水迷宫对2组大鼠学习记忆能力进行测试,取大鼠脑组织制作标本待检。酶联免疫吸附试验法检测HIF-1α、ICAM-1、IFN-γ及BDNF水平,Western blot检测磷酸化蛋白激酶(p-AKT)、Bax蛋白和B淋巴细胞瘤-2基因(B-cell lympho-ma-2,Bcl-2)蛋白表达水平。结果脑出血模型大鼠主要表现为肢体瘫痪,有追尾现象出现,大鼠不能正常站立或打滚,不能进行自发性活动,出现意识障碍;脑出血组大鼠逃避潜伏期长于正常组,穿越平台次数少于正常组(P<0.05);脑出血组大鼠HIF-1α、ICAM-1、IFN-γ水平高于正常组大鼠,且第14d脑出血组HIF-1α、ICAM-1、IFN-γ水平低于第7d(P<0.05);脑出血组大鼠BDNF水平低于正常组,第14d脑出血组BDNF水平高于第7d(P<0.05);脑出血组大鼠p-AKT、Bcl-2水平均高于正常组,Bax水平低于正常组(P<0.05)。结论 HIF-1α、ICAM-1、IFN-γ及BDNF在大鼠脑出血中均呈现异常表达。
Objective To investigate the expression level changes of hypoxia inducible factor-1 alpha(HIF-1α),intercellular adhesion molecule-1(ICAM-1),interferon-gamma(IFN-γ)and brain-derived neurotrophic factor(BDNF)in cerebral hemorrhage model rats.Methods Thirty healthy male SD rats were selected,of which 10 rats were normal,without any treatment.Another 20 rats were established for cerebral hemorrhage model.The learning and memory ability of the two groups were tested using Morris water maze,and the brain tissue of the rats were taken for specimen to be tested.The expression levels of phosphorylated protein kinase(p-akt),Bax protein and b-lymphoma-2(bcl-2)were detected by Western blot.Results The cerebral hemorrhage model rats were mainly manifested as paralysis of limbs,rear-end phenomenon,the rats could not stand or roll normally,could not carry out spontaneous activities,and presented the phenomenon of disturbance of consciousness.Compared the normal group,rats in the cerebral hemorrhage group had longer escape latency,and the number of crossing platforms was less in the cerebral hemorrhage group than that in the normal group(P<0.05).The levels of hif-α,icam-1 and ifn-γin the cerebral hemorrhage group were higher than those in the normal group,and the levels of hif-α,icam-1 and ifn-γin the 14 dcerebral hemorrhage group were lower than that in the 7 dgroup(P<0.05).The level of BDNF in the cerebral hemorrhage group was lower than that in the normal group,and the level of BDNF in the 14 dcerebral hemorrhage group was higher than that in the 7 dgroup(P<0.05).The levels of p-akt and bcl-2 in the cerebral hemorrhage group were higher than those in the normal group,and the level of Bax was lower than that in the normal group(P<0.05).Conclusion There were the abnormal expression levels of HIF-1α,ICAM-1,IFN-γand BDNF in the cerebral hemorrhage model rats.
Objective To investigate the expression level changes of hypoxia inducible factor-1 alpha(HIF-1α),intercellular adhesion molecule-1(ICAM-1),interferon-gamma(IFN-γ)and brain-derived neurotrophic factor(BDNF)in cerebral hemorrhage model rats.Methods Thirty healthy male SD rats were selected,of which 10 rats were normal,without any treatment.Another 20 rats were established for cerebral hemorrhage model.The learning and memory ability of the two groups were tested using Morris water maze,and the brain tissue of the rats were taken for specimen to be tested.The expression levels of phosphorylated protein kinase(p-akt),Bax protein and b-lymphoma-2(bcl-2)were detected by Western blot.Results The cerebral hemorrhage model rats were mainly manifested as paralysis of limbs,rear-end phenomenon,the rats could not stand or roll normally,could not carry out spontaneous activities,and presented the phenomenon of disturbance of consciousness.Compared the normal group,rats in the cerebral hemorrhage group had longer escape latency,and the number of crossing platforms was less in the cerebral hemorrhage group than that in the normal group(P<0.05).The levels of hif-α,icam-1 and ifn-γin the cerebral hemorrhage group were higher than those in the normal group,and the levels of hif-α,icam-1 and ifn-γin the 14 dcerebral hemorrhage group were lower than that in the 7 dgroup(P<0.05).The level of BDNF in the cerebral hemorrhage group was lower than that in the normal group,and the level of BDNF in the 14 dcerebral hemorrhage group was higher than that in the 7 dgroup(P<0.05).The levels of p-akt and bcl-2 in the cerebral hemorrhage group were higher than those in the normal group,and the level of Bax was lower than that in the normal group(P<0.05).Conclusion There were the abnormal expression levels of HIF-1α,ICAM-1,IFN-γand BDNF in the cerebral hemorrhage model rats.
引文
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[8]李丽敏,于芳苹,张黎,等.盐酸法舒地尔对脑出血大鼠炎性反应及继发性脑损伤的影响研究[J].中华神经医学杂志,2017,16(11):1081-1090.
[9]杨云芳,黄江,杨思进,等.蛭龙活血通瘀胶囊对脑出血大鼠HIF-1α与Bcl-2蛋白表达的影响[J].河南中医,2015,35(1):53-55.
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[11]邹伟,刘思妤,韩海伟,等.百会透曲鬓对脑出血急性期大鼠血清中VEGF、ICAM-1含量的影响[J].上海针灸杂志,2013,32(11):948-950.
[12]雷可殷,王冬燕,顾先君,等.通络解毒汤联合额部钻颅血肿引流术治疗痰热内闭清窍型脑出血疗效及对血清MMP-9,ICAM-1及脑水肿的影响[J].现代中西医结合杂志,2018,27(18):2010-2013.
[13]李其平,张珩,宋黎,等.醒脑静辅助超早期微创手术对基底节区脑出血患者外周血IFN-γ,TIM-3表达的影响[J].广西医科大学学报,2018,35(4):502-505.
[14]肖勇,夏正新,张苏宁,等.急性脑出血患者早期外周血干扰素-γ分泌水平与预后关系的研究[J].重庆医学,2018,47(1):57-59.
[15]张轶丹,赵建军,金曦,等.破血化瘀填精补髓方剂对脑出血大鼠模型神经营养因子BDNF表达的影响[J].中国中医急症,2015,24(1):1-3,23.
[16]梁慧,文国强.安脑丸对脑出血大鼠学习记忆功能及血肿周围BDNF、NGB表达的影响[J].卒中与神经疾病,2014,21(6):327-329,342.
[17]肖兴花.粒细胞集落刺激因子对实验性脑出血大鼠血肿周围组织中Bax及Bcl-2蛋白表达的影响[J].中国老年学杂志,2015,35(11):2927-2928,2929.
[18]李鹏,陶陶,罗开俭.依达拉奉对兔脑出血后血肿周围组织中Bax及Bcl-2蛋白表达的影响[J].第三军医大学学报,2014,36(6):596-599.
[19]吴晓光,仇志富,孟杰,等.补阳还五汤对脑出血模型大鼠脑组织PI3K,Akt,Bcl-2,BAX蛋白表达的影响[J].中国组织工程研究,2016,20(40):5933-5938.
[20]聂柳,王洪军,刘兴吉,等.脑出血大鼠颅内压及Bcl-2、Bax表达的变化与血肿周围水肿区细胞凋亡的关系[J].广东医学,2016,37(4):492-495.
[2]王晓萍,赵燊,林庆明,等.亚低温对大鼠脑出血后脑水肿及缺氧诱导因子-1α、血管内皮生长因子表达的影响[J].中华急诊医学杂志,2013,22(5):496-500.
[3]张极星,张艳国,赵亮,等.急性期脑出血患者血清ICAM-1,MMP-9,TNF-α,IL-6水平和出血灶周围水肿脑组织体积的相关性[J].山东医药,2017,57(27):58-60.
[4]毕胜,刘群,范佳,等.脑出血患者外周血干扰素-γ、细胞免疫球蛋白黏蛋白分子-3mRNA表达及意义[J].中国老年学杂志,2015,35(10):2674-2675.
[5]罗斌,唐启盛,李侠,等.益肾调气法对脑出血后抑郁大鼠脑内BDNF表达的影响[J].北京中医药大学学报,2014,37(6):393-396,后插3.
[6]吕超,秦龙,黄胜明.联合应用甘露醇、单唾液酸神经节苷脂对脑出血致脑水肿的临床疗效及对神经功能的影响[J].中国生化药物杂志,2017,37(1):172-175.
[7]Xue YZ,Li XX,Li L,et al.Curative effect and safety of intrathecal transplantation of neural stem cells for the treatment of cerebral hemorrhage[J].Genet Mol Res,2014,13(4):8294-8300.
[8]李丽敏,于芳苹,张黎,等.盐酸法舒地尔对脑出血大鼠炎性反应及继发性脑损伤的影响研究[J].中华神经医学杂志,2017,16(11):1081-1090.
[9]杨云芳,黄江,杨思进,等.蛭龙活血通瘀胶囊对脑出血大鼠HIF-1α与Bcl-2蛋白表达的影响[J].河南中医,2015,35(1):53-55.
[10]赵红领,李磊,苗成,等.丹参酮ⅡA对脑出血大鼠脑组织HIF-1α和VEGF表达的影响[J].中风与神经疾病杂志,2017,34(2):130-132.
[11]邹伟,刘思妤,韩海伟,等.百会透曲鬓对脑出血急性期大鼠血清中VEGF、ICAM-1含量的影响[J].上海针灸杂志,2013,32(11):948-950.
[12]雷可殷,王冬燕,顾先君,等.通络解毒汤联合额部钻颅血肿引流术治疗痰热内闭清窍型脑出血疗效及对血清MMP-9,ICAM-1及脑水肿的影响[J].现代中西医结合杂志,2018,27(18):2010-2013.
[13]李其平,张珩,宋黎,等.醒脑静辅助超早期微创手术对基底节区脑出血患者外周血IFN-γ,TIM-3表达的影响[J].广西医科大学学报,2018,35(4):502-505.
[14]肖勇,夏正新,张苏宁,等.急性脑出血患者早期外周血干扰素-γ分泌水平与预后关系的研究[J].重庆医学,2018,47(1):57-59.
[15]张轶丹,赵建军,金曦,等.破血化瘀填精补髓方剂对脑出血大鼠模型神经营养因子BDNF表达的影响[J].中国中医急症,2015,24(1):1-3,23.
[16]梁慧,文国强.安脑丸对脑出血大鼠学习记忆功能及血肿周围BDNF、NGB表达的影响[J].卒中与神经疾病,2014,21(6):327-329,342.
[17]肖兴花.粒细胞集落刺激因子对实验性脑出血大鼠血肿周围组织中Bax及Bcl-2蛋白表达的影响[J].中国老年学杂志,2015,35(11):2927-2928,2929.
[18]李鹏,陶陶,罗开俭.依达拉奉对兔脑出血后血肿周围组织中Bax及Bcl-2蛋白表达的影响[J].第三军医大学学报,2014,36(6):596-599.
[19]吴晓光,仇志富,孟杰,等.补阳还五汤对脑出血模型大鼠脑组织PI3K,Akt,Bcl-2,BAX蛋白表达的影响[J].中国组织工程研究,2016,20(40):5933-5938.
[20]聂柳,王洪军,刘兴吉,等.脑出血大鼠颅内压及Bcl-2、Bax表达的变化与血肿周围水肿区细胞凋亡的关系[J].广东医学,2016,37(4):492-495.