益母草碱对脑缺血大鼠海马小清蛋白表达的影响
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摘要
目的:研究脑缺血对大鼠海马部位小清蛋白(PV)表达的影响和益母草碱(Leo)的干预效果。方法:选取30只SD雄性大鼠随机分为假手术组、脑缺血模型组、Leo低、中、高剂量组,通过结扎双侧颈总动脉(30min)建立急性脑缺血模型,腹腔注射不同剂量Leo,1次/d,术前连续给药3 d。采用旷场试验和免疫组织化学染色方法,探究脑缺血及Leo预处理干预对大鼠的行为学变化以及大鼠脑内海马区PV表达的影响。结果:与假手术组比较,缺血组大鼠旷场试验分数显著降低(P <0. 05)、海马各区的PV阳性细胞数显著减少(P <0. 01),Leo组大鼠旷场试验分数升高,其中高剂量组最明显(P <0. 05); PV阳性细胞数增加,其中高剂量组最明显(P <0. 01)。结论:短暂性脑缺血会影响大鼠的行为学并导致海马PV阳性神经元数量急剧减少,Leo对缺血大鼠的行为有积极作用,并有效改善缺血大鼠海马PV阳性神经元的损伤。
Objective: To investigate the effect of cerebral ischemia on the expression of parvalbumin(PV) in rat brain and the intervention effect of Leonurine(Leo). Methods: Thirty SD male rats were randomly divided into sham operation group,cerebral ischemia model group,low,medium and high dose groups of leonurine. The model of acute cerebral ischemia was established by ligation of bilateral common carotid arteries(30 min). Different doses of Leo were injected intraperitoneally for 1 time/d and was administered continuously for 3 days before surgery. The open field test and immunohistochemical staining was used to investigate the effects of cerebral ischemia and Leo preconditioning on the behavioral changes and expression of PV in the hippocampus of rats. Results: Compared with the sham operation group,the scores of open field test in ischemic group decreased significantly(P < 0. 05) and the number of PV positive cells in the hippocampus of the ischemic group was significantly decreased(P < 0. 01). The scores of open field test in Leo group increased and the high dose group was the most significant(P < 0. 05); The number of PV positive cells in the Leo group increased,and the high dose group was the most significant(P < 0. 01). Conclusion: Transient cerebral ischemia can affect the behavior of rats and lead to a sharp decrease in the number of PV-positive neurons in hippocampus. Leo has a positive effect on the behavior of ischemic rats and can effectively improve the damage of PV-positive neurons in hippocampus of ischemic rats.
Objective: To investigate the effect of cerebral ischemia on the expression of parvalbumin(PV) in rat brain and the intervention effect of Leonurine(Leo). Methods: Thirty SD male rats were randomly divided into sham operation group,cerebral ischemia model group,low,medium and high dose groups of leonurine. The model of acute cerebral ischemia was established by ligation of bilateral common carotid arteries(30 min). Different doses of Leo were injected intraperitoneally for 1 time/d and was administered continuously for 3 days before surgery. The open field test and immunohistochemical staining was used to investigate the effects of cerebral ischemia and Leo preconditioning on the behavioral changes and expression of PV in the hippocampus of rats. Results: Compared with the sham operation group,the scores of open field test in ischemic group decreased significantly(P < 0. 05) and the number of PV positive cells in the hippocampus of the ischemic group was significantly decreased(P < 0. 01). The scores of open field test in Leo group increased and the high dose group was the most significant(P < 0. 05); The number of PV positive cells in the Leo group increased,and the high dose group was the most significant(P < 0. 01). Conclusion: Transient cerebral ischemia can affect the behavior of rats and lead to a sharp decrease in the number of PV-positive neurons in hippocampus. Leo has a positive effect on the behavior of ischemic rats and can effectively improve the damage of PV-positive neurons in hippocampus of ischemic rats.
引文
[1]Heir JJ,Wintermark M.New developments in clinical ischemic stroke prevention and treatment and their imaging implications[J].J Cereb Blood Flow Metab,2018,38(9):1533-1550.DOI:10.1177/0271678X17694046.
[2]Zhang L,Wang L,Chen WW,et al.Neural differentiation of human wharton’s jelly‐derived mesenchymal stem cells improves the recovery of neurological function after transplantation in ischemic stroke rats[J].Neural Regen Res,2017,12(7):1103-1110.DOI:10.4103/1673-5374.211189.
[3]Torrey EF,Barci BM,Webster MJ,et al.Neurochemical markers for schizophrenia,bipolar disorder,and major depression in postmortem brains[J].Biol Psychiatry,2005,57(3):252-260.DOI:10.1016/j.biopsych.2004.10.019.
[4]Park DJ,Koh PO.Diabetes aggravates decreases in hippocalcin and parvalbumin expression in focal cerebral ischemia[J].Neurosci Lett,2018,662:189-194.DOI:10.1016/j.neulet.2017.10.039.
[5]Khaksari M,Mehrjerdi FZ,Rezvani ME,et al.The role of erythropoietin in remote renal preconditioning on hippocampus ischemia/reperfusion injury[J].J Physiol Sci,2017,67(1):163-171.DOI:10.1007/s12576-016-0451-6.
[6]Cabungcal JH,Counotte DS,Lewis E,et al.Juvenile antioxidant treatment prevents adult deficits in a developmental model of schizophrenia[J].Neuron,2014,83(5):1073-1084.DOI:10.1016/j.neuron.2014.07.028.
[7]Steidl S,Wang H,Wise RA.Lesions of cholinergic pedunculopontine tegmental nucleus neurons fail to affect cocaine or heroin selfadministration or conditioned place preference in rats[J].PLo SOne,2014,9(1):e84412.DOI:10.1371/journal.pone.0084412.
[8]Chen Z,Jiang B,Ru X,et al.Mortality of stroke and its subtypes in China:Results from a nationwide population-based survey[J].Neuroepidemiology,2017,48(3-4):95-102.DOI:10.1159/000477494.
[9]Der Simonian R,Laird N.Meta-analysis in clinical trials revisited[J].Contemp Clin Trials,2015,45(Pt A):139-45.DOI:10.1016/j.cct.2015.09.002.
[10]Benjamin EJ,Blaha MJ,Chiuve SE,et al.Heart disease and stroke statistics-2017 update:A report from the American heart association[J].Circulation,2017,135(10):e146-e603.DOI:10.1161/CIR.0000000000000485.
[11]Martinez-Diaz JA,Garcia LI,Hernández-ME,et al.Effects on locomotion and memory in 2 models of cerebral hypoperfusion in male Wistar rats[J].Neurologia,2015,30(7):407-415.DOI:10.1016/j.nrl.2014.03.001.
[12]Bertolino G,De Araujo FL,Souza HC,et al.Neuropathology and behavioral impairments after bilateral global ischemia surgery and exposure to static magnetic field:Evidence in the motor cortex,the hippocampal Ca1 region and the neostriatum[J].Int J Radiat Biol,2013,89(8):595-601.DOI:10.3109/09553002.2013.784422.
[13]Zanier ER,Pischiutta F,Villa P,et al.Six-month ischemic mice show sensorimotor and cognitive deficits associated with brain atrophy and axonal disorganization[J].CNS Neurosci The,.2013,19(9):695-704.DOI:10.1111/cns.12128.
[14]刘小蒙,王荣亮,罗玉敏.大鼠脑缺血神经功能缺损行为学评价的研究进展[J].中国脑血管病杂志,2012,9(4):208-212.DOI:10.3969/j.issn.1672-5921.2012.04.009.
[15]Sommer CJ.Ischemic stroke:experimental models and reality[J].Acta Neuropathol,2017,133(2):245-261.DOI:10.1007/s00401-017-1667-0.
[16]Du H,Ming X,Zhou S.Pre-treatment with spermine for acute cerebral ischemia/reperfusion injuries[J].Exp Ther Med,2017,14(1):169-172.DOI:10.3892/etm.2017.4455.
[17]Himeda T,Hayakawa N,Tounai H,et al.Alterations of interneurons of the gerbil hippocampus after transient cerebral ischemia:effect of pitavastatin[J].Neuropsychopharmacology,2005,30(11):2014-25.DOI:10.1038/sj.npp.1300798.
[18]Fagel DM,Ganat Y,Cheng E,et al.Fgfr1 is required for cortical regeneration and repair after perinatal hypoxia[J].J Neurosci,2009,29(4):1202-1211.DOI:10.1523/JNEUROSCI.4516-08.2009.
[19]Zhang QY,Wang ZJ,Sun DM,et al.Novel therapeutic effects of leonurine on ischemic stroke:New mechanisms of BBB integrity[J].Oxid Med Cell Longev,2017,2017:7150376.DOI:10.1155/2017/7150376.
[2]Zhang L,Wang L,Chen WW,et al.Neural differentiation of human wharton’s jelly‐derived mesenchymal stem cells improves the recovery of neurological function after transplantation in ischemic stroke rats[J].Neural Regen Res,2017,12(7):1103-1110.DOI:10.4103/1673-5374.211189.
[3]Torrey EF,Barci BM,Webster MJ,et al.Neurochemical markers for schizophrenia,bipolar disorder,and major depression in postmortem brains[J].Biol Psychiatry,2005,57(3):252-260.DOI:10.1016/j.biopsych.2004.10.019.
[4]Park DJ,Koh PO.Diabetes aggravates decreases in hippocalcin and parvalbumin expression in focal cerebral ischemia[J].Neurosci Lett,2018,662:189-194.DOI:10.1016/j.neulet.2017.10.039.
[5]Khaksari M,Mehrjerdi FZ,Rezvani ME,et al.The role of erythropoietin in remote renal preconditioning on hippocampus ischemia/reperfusion injury[J].J Physiol Sci,2017,67(1):163-171.DOI:10.1007/s12576-016-0451-6.
[6]Cabungcal JH,Counotte DS,Lewis E,et al.Juvenile antioxidant treatment prevents adult deficits in a developmental model of schizophrenia[J].Neuron,2014,83(5):1073-1084.DOI:10.1016/j.neuron.2014.07.028.
[7]Steidl S,Wang H,Wise RA.Lesions of cholinergic pedunculopontine tegmental nucleus neurons fail to affect cocaine or heroin selfadministration or conditioned place preference in rats[J].PLo SOne,2014,9(1):e84412.DOI:10.1371/journal.pone.0084412.
[8]Chen Z,Jiang B,Ru X,et al.Mortality of stroke and its subtypes in China:Results from a nationwide population-based survey[J].Neuroepidemiology,2017,48(3-4):95-102.DOI:10.1159/000477494.
[9]Der Simonian R,Laird N.Meta-analysis in clinical trials revisited[J].Contemp Clin Trials,2015,45(Pt A):139-45.DOI:10.1016/j.cct.2015.09.002.
[10]Benjamin EJ,Blaha MJ,Chiuve SE,et al.Heart disease and stroke statistics-2017 update:A report from the American heart association[J].Circulation,2017,135(10):e146-e603.DOI:10.1161/CIR.0000000000000485.
[11]Martinez-Diaz JA,Garcia LI,Hernández-ME,et al.Effects on locomotion and memory in 2 models of cerebral hypoperfusion in male Wistar rats[J].Neurologia,2015,30(7):407-415.DOI:10.1016/j.nrl.2014.03.001.
[12]Bertolino G,De Araujo FL,Souza HC,et al.Neuropathology and behavioral impairments after bilateral global ischemia surgery and exposure to static magnetic field:Evidence in the motor cortex,the hippocampal Ca1 region and the neostriatum[J].Int J Radiat Biol,2013,89(8):595-601.DOI:10.3109/09553002.2013.784422.
[13]Zanier ER,Pischiutta F,Villa P,et al.Six-month ischemic mice show sensorimotor and cognitive deficits associated with brain atrophy and axonal disorganization[J].CNS Neurosci The,.2013,19(9):695-704.DOI:10.1111/cns.12128.
[14]刘小蒙,王荣亮,罗玉敏.大鼠脑缺血神经功能缺损行为学评价的研究进展[J].中国脑血管病杂志,2012,9(4):208-212.DOI:10.3969/j.issn.1672-5921.2012.04.009.
[15]Sommer CJ.Ischemic stroke:experimental models and reality[J].Acta Neuropathol,2017,133(2):245-261.DOI:10.1007/s00401-017-1667-0.
[16]Du H,Ming X,Zhou S.Pre-treatment with spermine for acute cerebral ischemia/reperfusion injuries[J].Exp Ther Med,2017,14(1):169-172.DOI:10.3892/etm.2017.4455.
[17]Himeda T,Hayakawa N,Tounai H,et al.Alterations of interneurons of the gerbil hippocampus after transient cerebral ischemia:effect of pitavastatin[J].Neuropsychopharmacology,2005,30(11):2014-25.DOI:10.1038/sj.npp.1300798.
[18]Fagel DM,Ganat Y,Cheng E,et al.Fgfr1 is required for cortical regeneration and repair after perinatal hypoxia[J].J Neurosci,2009,29(4):1202-1211.DOI:10.1523/JNEUROSCI.4516-08.2009.
[19]Zhang QY,Wang ZJ,Sun DM,et al.Novel therapeutic effects of leonurine on ischemic stroke:New mechanisms of BBB integrity[J].Oxid Med Cell Longev,2017,2017:7150376.DOI:10.1155/2017/7150376.