依达拉奉对大鼠脑缺血再灌注损伤的机制研究
|
摘要
目的探讨依达拉奉对脑缺血再灌注大鼠PDCD-5蛋白表达的影响。方法将体重为250～280 g的健康雄性SD大鼠78只按照随机数字表法分为空白对照组(n=6,生理盐水,3 mg/kg,2次/d,腹腔内注射)、假手术组(n=24,生理盐水,3 mg/kg,2次/d,腹腔内注射)、脑缺血再灌注组(n=24,生理盐水,3 mg/kg,2次/d,腹腔内注射)及药物干预组(n=24,依达拉奉3 mg/kg,2次/d,腹腔内注射),后三组再随机分为6 h组、1 d组、3 d组、7 d组。选择改良Longa法建立脑缺血再灌注模型。比较各组神经功能缺损情况、脑梗死面积及PDCD-5和Caspase-3蛋白在不同时期海马组织中的表达。结果脑缺血再灌注组脑梗死灶较假手术组明显增加(P <0.05),药物干预组脑梗死灶较脑缺血再灌注组明显减少(P <0.05)。同时,不同时间点脑缺血再灌注组的PDCD-5、Caspase-3蛋白表达均高于假手术组和药物干预组,差异均有统计学意义(P <0.05)。结论依达拉奉对脑缺血再灌注大鼠海马组织中PDCD-5的表达起抑制作用,并对大鼠脑缺血再灌注损伤起脑保护作用。
Objective To investigate the effect of Edaravone on the expression of PDCD-5 protein in rats with cerebral ischemia reperfusion. Methods Seventy-eight healthy male SD rats with a healthy weight of 250-280 g were randomly divided into blank control group(n = 6, normal saline, 3 mg/kg, twice a day, intraperitoneal injection), sham operation group(n = 24, normal saline, 3 mg/kg, twice a day, intraperitoneal injection), cerebral ischemia reperfusion group(n = 24,normal saline, 3 mg/kg, twice a day, intraperitoneal injection) and drug intervention group(n = 24, Edaravone 3 mg/kg,twice a day, intraperitoneal injection) according to random number table method, and the latter 3 groups were randomly divided into 6 h group, 1 d group, 3 d group and 7 d group. A modified Longa method was used to establish cerebral ischemia-reperfusion model. The neurological deficit, the acreage of cerebral infarction and the expression of PDCD-5 and Caspase-3 protein in hippocampus of different periods were compared. Results The cerebral infarction in cerebral ischemia reperfusion group was significantly increased compared with sham operation group(P < 0.05); the cerebral infarction in drug intervention group was significantly reduced compared with cerebral ischemia reperfusion group(P <0.05). At the same time, the expression of PDCD-5, Caspase-3 protein in cerebral ischemia-reperfusion group at different time points was higher than those in corresponding sham-operation group and corresponding drug intervention group(P < 0.05). Conclusion Edaravone can inhibit the expression of PDCD-5 in the hippocampus of rats with cerebral ischemia-reperfusion, and protect the brain against cerebral ischemia-reperfusion injury in rats.
Objective To investigate the effect of Edaravone on the expression of PDCD-5 protein in rats with cerebral ischemia reperfusion. Methods Seventy-eight healthy male SD rats with a healthy weight of 250-280 g were randomly divided into blank control group(n = 6, normal saline, 3 mg/kg, twice a day, intraperitoneal injection), sham operation group(n = 24, normal saline, 3 mg/kg, twice a day, intraperitoneal injection), cerebral ischemia reperfusion group(n = 24,normal saline, 3 mg/kg, twice a day, intraperitoneal injection) and drug intervention group(n = 24, Edaravone 3 mg/kg,twice a day, intraperitoneal injection) according to random number table method, and the latter 3 groups were randomly divided into 6 h group, 1 d group, 3 d group and 7 d group. A modified Longa method was used to establish cerebral ischemia-reperfusion model. The neurological deficit, the acreage of cerebral infarction and the expression of PDCD-5 and Caspase-3 protein in hippocampus of different periods were compared. Results The cerebral infarction in cerebral ischemia reperfusion group was significantly increased compared with sham operation group(P < 0.05); the cerebral infarction in drug intervention group was significantly reduced compared with cerebral ischemia reperfusion group(P <0.05). At the same time, the expression of PDCD-5, Caspase-3 protein in cerebral ischemia-reperfusion group at different time points was higher than those in corresponding sham-operation group and corresponding drug intervention group(P < 0.05). Conclusion Edaravone can inhibit the expression of PDCD-5 in the hippocampus of rats with cerebral ischemia-reperfusion, and protect the brain against cerebral ischemia-reperfusion injury in rats.
引文
[1]中国卒中学会,中国卒中学会神经介入学会,中华预防医学卒中预防与控制专业委员会介入学者.急性缺血性卒中血管内治疗中国指南2015[J].中国卒中杂志,2015,10(7):590.
[2]Guo MF,Yu JZ,Ma CG.Mechanisms related to neuron injury and death in cerebral hypoxic ischaemia[J].Folia Neuropathol,2015,49(2):78-87.
[3]Ma XD,Song JN,Zhang M,et al.Advances in research of the neuroprotective mechanisms of cerebral ischemic postconditioning[J].Int J Neurosci,2015,125(3):161-169.
[4]Widgerow AD.Ischemia-Reperfusion injury influencing the microcirculatory and cellular environment[J].Ann Plast Surg,2014,72(2):253-260.
[5]刘斌,董晓柳.急性脑缺血大鼠海马CA1区细胞凋亡与Caspase-3及Caspase-10蛋白表达的相关性[J].现代预防医学,2012,39(14):2662-2664.
[6]Pandya JD,Sullivan PG,Pettigrew LC.Focal cerebral ischemia and mitochondrial dysfunction in the TNFα-transgenic rat[J].Brain Research,2011,1384:151-160.
[7]王立茹,王敏,崔建英,等.急性髓性白血病PDCD-5的表达及其临床意义[J].中国实验血液学杂志,2015,23(1):24-28.
[8]王林,王瑞刚,王原.丁苯酞对大鼠脑缺血再灌注损伤模型细胞凋亡作用及机制初步研究[J].生物医学工程与临床,2017,21(5):471-475.
[9]Longa EZ,Weinstein PR,Carlson S.Reversible middle cerebral artery occlusion without craniectomy in rats[J].Stroke,1989,20(1):84-91.
[10]梁婷婷,于云海,董延磊,等.PDCD5在人子宫内膜癌中的表达及对细胞凋亡的影响[J].实用癌症杂志,2016,31(11):1749-1753.
[11]刘永蕊,刘静蕾,唐国栋,等.PDCD-5基因与非小细胞肺癌的研究进展[J].中国肿瘤,2015,24(4):302-306.
[12]徐玲,蔡银链,许朝祥.氯吡格雷对大鼠心肌缺血/再灌注心肌细胞凋亡及氧自由基的作用及机制[J].中国老年学杂志,2017,37(16):3942-3944.
[13]金涛,何前进,毛伟明,等.HIF-2α对PDCD5的调节及其对肝癌细胞凋亡影响的研究[J].肝胆外科杂志,2018,26(1):65-70.
[14]Lu Jianfei,Yan Junhao,Yang Lei,et al.Knockdown of programmed cell death 5(PDCD-5)attenuate brain microcirculation disturbance after middle cerebral atery occlusion in mice[C]//The 18th congress of the international Federation of Associations of Anatomists,2014.
[15]卢磊,刘晓丹,张培影.内质网应激介导的细胞凋亡与心力衰竭[J].中华老年心脑血管病杂志,2018,20(4):432-436.
[16]Essers PB,Klasson TD,Pereboom TC,et al.The von HippeLindau tumor suppressor regulates programmed cell death 5-mediated degradation of Mdm2[J].Oncogene,2015,34(6):771-779.
[17]王淑玲,刘佳,邓景贵,等.强制性运动疗法对脑卒中大鼠神经功能的影响[J].中国老年学杂志,2017,37(18):4440-4443.
[18]姚期,余资江,孙宝飞,等.松树皮提取物对小鼠脑缺血再灌注损伤的保护作用及机制研究[J].中国实验动物学报,2017,25(6):632-636.
[19]Pendergrass KD,Boopathy AV,Seshadri G,et al.Acute preconditioning of cardiac progenitor cells with hydrogen peroxide enhances angiogenic pathways following ischemic-reperfusion injury[J].Stem Cell Dev,2013,22(17):2414-2424.
[20]Smith PD,Ben MT,Puskas F,et al.Presevation of motor function after spinal cord ischemic and reperfusion injury through microglial inhibition[J].Ann Thorac Sury,2013,95(5):1647-1653.
[2]Guo MF,Yu JZ,Ma CG.Mechanisms related to neuron injury and death in cerebral hypoxic ischaemia[J].Folia Neuropathol,2015,49(2):78-87.
[3]Ma XD,Song JN,Zhang M,et al.Advances in research of the neuroprotective mechanisms of cerebral ischemic postconditioning[J].Int J Neurosci,2015,125(3):161-169.
[4]Widgerow AD.Ischemia-Reperfusion injury influencing the microcirculatory and cellular environment[J].Ann Plast Surg,2014,72(2):253-260.
[5]刘斌,董晓柳.急性脑缺血大鼠海马CA1区细胞凋亡与Caspase-3及Caspase-10蛋白表达的相关性[J].现代预防医学,2012,39(14):2662-2664.
[6]Pandya JD,Sullivan PG,Pettigrew LC.Focal cerebral ischemia and mitochondrial dysfunction in the TNFα-transgenic rat[J].Brain Research,2011,1384:151-160.
[7]王立茹,王敏,崔建英,等.急性髓性白血病PDCD-5的表达及其临床意义[J].中国实验血液学杂志,2015,23(1):24-28.
[8]王林,王瑞刚,王原.丁苯酞对大鼠脑缺血再灌注损伤模型细胞凋亡作用及机制初步研究[J].生物医学工程与临床,2017,21(5):471-475.
[9]Longa EZ,Weinstein PR,Carlson S.Reversible middle cerebral artery occlusion without craniectomy in rats[J].Stroke,1989,20(1):84-91.
[10]梁婷婷,于云海,董延磊,等.PDCD5在人子宫内膜癌中的表达及对细胞凋亡的影响[J].实用癌症杂志,2016,31(11):1749-1753.
[11]刘永蕊,刘静蕾,唐国栋,等.PDCD-5基因与非小细胞肺癌的研究进展[J].中国肿瘤,2015,24(4):302-306.
[12]徐玲,蔡银链,许朝祥.氯吡格雷对大鼠心肌缺血/再灌注心肌细胞凋亡及氧自由基的作用及机制[J].中国老年学杂志,2017,37(16):3942-3944.
[13]金涛,何前进,毛伟明,等.HIF-2α对PDCD5的调节及其对肝癌细胞凋亡影响的研究[J].肝胆外科杂志,2018,26(1):65-70.
[14]Lu Jianfei,Yan Junhao,Yang Lei,et al.Knockdown of programmed cell death 5(PDCD-5)attenuate brain microcirculation disturbance after middle cerebral atery occlusion in mice[C]//The 18th congress of the international Federation of Associations of Anatomists,2014.
[15]卢磊,刘晓丹,张培影.内质网应激介导的细胞凋亡与心力衰竭[J].中华老年心脑血管病杂志,2018,20(4):432-436.
[16]Essers PB,Klasson TD,Pereboom TC,et al.The von HippeLindau tumor suppressor regulates programmed cell death 5-mediated degradation of Mdm2[J].Oncogene,2015,34(6):771-779.
[17]王淑玲,刘佳,邓景贵,等.强制性运动疗法对脑卒中大鼠神经功能的影响[J].中国老年学杂志,2017,37(18):4440-4443.
[18]姚期,余资江,孙宝飞,等.松树皮提取物对小鼠脑缺血再灌注损伤的保护作用及机制研究[J].中国实验动物学报,2017,25(6):632-636.
[19]Pendergrass KD,Boopathy AV,Seshadri G,et al.Acute preconditioning of cardiac progenitor cells with hydrogen peroxide enhances angiogenic pathways following ischemic-reperfusion injury[J].Stem Cell Dev,2013,22(17):2414-2424.
[20]Smith PD,Ben MT,Puskas F,et al.Presevation of motor function after spinal cord ischemic and reperfusion injury through microglial inhibition[J].Ann Thorac Sury,2013,95(5):1647-1653.