后膜骨架蛋白1a在小鼠脑缺血再灌注损伤中的作用
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摘要
目的探讨后膜骨架蛋白1a(Homer 1a)在小鼠脑缺血再灌注损伤中的作用。方法以Homer1a基因敲除小鼠为研究对象,复制脑缺血再灌注小鼠模型,根据行为学评分标准评价小鼠脑缺血再灌注的损伤程度。运用TTC染色法观察计算小鼠脑梗死体积。Tunel法检测脑缺血再灌注小鼠脑组织中细胞凋亡情况。GFAP法检测星形胶质细胞的增殖情况。Western blot检测小鼠脑组织中IL-1β、TNF-α、IL-6水平。结果实验组小鼠行为学评分高于脑缺血组,说明Homer 1a基因敲除小鼠脑缺血再灌注损伤较脑缺血组更为严重。实验组小鼠脑梗死体积与脑缺血组比较,差异有统计学意义(P<0.05),实验组增多。实验组小鼠脑组织细胞凋亡高于脑缺血组(P<0.05)。实验组和脑缺血组小鼠脑组织中星形胶质细胞数都高于正常组(P<0.05),而实验组小鼠脑组织中星型胶质细胞数量低于脑缺血组。实验组小鼠脑组织中IL-1β、TNF-α、IL-6表达水平均高于脑缺血组(P<0.05)。结论 Homer 1a基因敲除小鼠可以加重脑缺血再灌注后的损伤。Homer 1a可以减弱脑缺血再灌注损伤。
Objective To investigate the effect of Homer 1a on cerebral ischemia-reperfusion injury in mice. Methods Homer 1a knockout mice were used as the research objects to construct the model of cerebral ischemia-reperfusion in mice. The degree of cerebral ischemia-reperfusion injury in mice was evaluated based on the behavioral score. TTC staining was used to observe and calculate the volume of cerebral infarction. Apoptosis of the brain tissues of the mice was detected by Tunel. The proliferation of astrocytes was detected by GFAP method. The levels of IL-1β, TNF-α and IL-6 in the mouse brain were detected by Western blot. Results The behavioral score of the experimental group was significantly higher than that of the cerebral ischemia group, indicating that cerebral ischemia-reperfusion injury of the Homer 1a gene knockout mice were more severe than that of the cerebral ischemia group. The cerebral infarction volume in the experimental group was significantly larger than that in the cerebral ischemia group(P < 0.05). The apoptosis rate of brain cells in the experimental group was significantly higher than that in the cerebral ischemia group(P < 0.05). The number of brain astrocytes in the experimental group and the cerebral ischemia group was larger than that in the normal group(P < 0.05), while the number of brain astrocytes in the experimental group was smaller than that in the cerebral ischemia group. The expression levels of IL-6, TNF-α and IL-1β in the brain tissue of the experimental group were higher than those in the cerebral ischemia group(P < 0.05). Conclusions Homer 1a knockout can aggravate the injury after cerebral ischemia and reperfusion in mice. Homer 1a can attenuate cerebral ischemia-reperfusion injury.
Objective To investigate the effect of Homer 1a on cerebral ischemia-reperfusion injury in mice. Methods Homer 1a knockout mice were used as the research objects to construct the model of cerebral ischemia-reperfusion in mice. The degree of cerebral ischemia-reperfusion injury in mice was evaluated based on the behavioral score. TTC staining was used to observe and calculate the volume of cerebral infarction. Apoptosis of the brain tissues of the mice was detected by Tunel. The proliferation of astrocytes was detected by GFAP method. The levels of IL-1β, TNF-α and IL-6 in the mouse brain were detected by Western blot. Results The behavioral score of the experimental group was significantly higher than that of the cerebral ischemia group, indicating that cerebral ischemia-reperfusion injury of the Homer 1a gene knockout mice were more severe than that of the cerebral ischemia group. The cerebral infarction volume in the experimental group was significantly larger than that in the cerebral ischemia group(P < 0.05). The apoptosis rate of brain cells in the experimental group was significantly higher than that in the cerebral ischemia group(P < 0.05). The number of brain astrocytes in the experimental group and the cerebral ischemia group was larger than that in the normal group(P < 0.05), while the number of brain astrocytes in the experimental group was smaller than that in the cerebral ischemia group. The expression levels of IL-6, TNF-α and IL-1β in the brain tissue of the experimental group were higher than those in the cerebral ischemia group(P < 0.05). Conclusions Homer 1a knockout can aggravate the injury after cerebral ischemia and reperfusion in mice. Homer 1a can attenuate cerebral ischemia-reperfusion injury.
引文
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[20]IRAM T,RAMIREZ-ORTIZ Z,BYRNE M H,et al.Megf10 is a receptor for C1Q that mediates clearance of apoptotic cells by astrocytes[J].Journal of Neuroscience the Official Journal of the Society for Neuroscience,2016,36(19):5185-5192.
[2]ZHANG H,YANG L,FENG Q,et al.Association Between VKORC1,Gene polymorphisms and ischemic cerebrovascular disease in chinese han population[J].Journal of Molecular Neuroscience,2014,53(2):166-170.
[3]CHI O Z,BARSOUM S,KANG H R,et al.Local O2,Balance in cerebral ischemia–reperfusion improved during pentobarbital compared with isoflurane anesthesia[J].Journal of Stroke&Cerebrovascular Diseases the Official Journal of National Stroke Association,2015,24(6):1196-1203.
[4]WANG Q,CHIKINA M D,PINCAS H,et al.Homerla lternative splicing is regulated by gonadotropin-releasing hormone and modulates gonadotropin gene expression[J].Molecular&Cellular Biology,2014,34(10):1747-1756.
[5]TANG A H,ALGER B E.Homer protein-metabotropic glutamate receptor binding regulates endocannabinoid signaling and affects hyperexcitability in a mouse model of fragile X syndrome[J].Journal of Neuroscience,the Official Journal of the Society for Neuroscience,2015,35(9):3938-3945.
[6]王振富,杨付明.黄芪多糖对大鼠全脑缺血再灌注损伤的保护作用[J].中国老年学杂志,2016,36(05):1059-1060.
[7]BANERJEE A,LUONG J A,HO A,et al.Overexpression of Homer1a in the basal and lateral amygdala impairs fear conditioning and induces an autism-like social impairment[J].Molecular Autism,2016,7(1):1-15.
[8]苏敬敬,陶晓晓,舒良,等.Homer1b/c在缺氧复氧损伤神经元中的保护作用研究[J].现代生物医学进展,2015,15(19):3605-3608.
[9]RUEGSEGGER C,STUCKI D M,STEINER S,et al.Impaired m TORC 1-dependent expression of homer-3 influences SCA1pathophysiology[J].Neuron,2016,89(1):129-146.
[10]GUO W,MOLINARO G,COLLINS K A,et al.Selective disruption of metabotropic glutamate recept or 5-homer interactions mimics phenotypes of fragile X syndrome in mice[J].Journal of Neuroscience the Official Journal of the Society for Neuroscience,2016,36(7):2131-2147.
[11]BEEN L E,MOORE K M,KENNEDY B C,et al.Metabotropic glutamate receptor and fragile X signaling in a female model of escalated aggression[J].Biological Psychiatry,2015,79(8):685-692.
[12]褚立梅,杨光辉,董丽娟,等.右美托咪定对大鼠移植肝缺血/再灌注所致急性肺损伤中细胞凋亡及CCAAT增强子结合蛋白同源蛋白的影响[J].中国中西医结合急救杂志,2015,22(3):262-266.
[13]戴勇,陶立德,薛同敏,等.缺血预处理对大鼠肝脏缺血再灌注损伤后细胞凋亡的影响[J].中国现代普通外科进展,2015,18(03):169-172.
[14]ZHAO S D,CHEN Y,DONG Y F,et al.Effects of soybean isoflavones on apoptosis of rat hippocampal neurons after global cerebral ischemia/reperfusion[J].Journal of Shanghai Jiaotong University,2015,35(4):521-529.
[15]KABOURIDIS P,LASRADO R,MCCALLUM S,et al.Microbiota controls the homeostasis of glial cells in the gut lamina propria[J].Neuron,2015,85(2):289-295.
[16]APOSTOLOVA N,FUNES H A,BLASGARCIA A,et al.Involvement of nitric oxide in the mitochondrial action of efavirenz:a differential effect on neurons and glial cells[J].Journal of Infectious Diseases,2015,211(12):1953-1958.
[17]LUO X,HE J J.Cell–cell contact viral transfer contributes to HIV infection and persistence in astrocytes[J].Journal of Neurovirology,2015,21(1):66-80.
[18]GABEL S,KONCINA E,DORBAN G,et al.Inflammation promotes a conversion of astrocytes into neural progenitor cells via NF-κB activation[J].Molecular Neurobiology,2015,17(7):1-15.
[19]VIADER A,BLANKMAN J,ZHONG P,et al.Metabolic interplay between astrocytes and neurons regulates endocannabinoid action[J].Cell Reports,2015,12(5):798-808.
[20]IRAM T,RAMIREZ-ORTIZ Z,BYRNE M H,et al.Megf10 is a receptor for C1Q that mediates clearance of apoptotic cells by astrocytes[J].Journal of Neuroscience the Official Journal of the Society for Neuroscience,2016,36(19):5185-5192.