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作 者:梁新[1] 李佳庆 王玉保 曹晓光 霍虹达 梁德海[1] LIANG Xin;LI Jia-qing;WANG Yu-bao;CAO Xiao-guang;HUO Hong-da;LIANG De-hai(Department of Neurosurgery,Cangzhou Central Hospital,Cangzhou 061000,Hebei Province,China)
机构地区:[1]沧州市中心医院神经外科,河北沧州061000
出 处:《中国临床药理学杂志》2024年第21期3119-3123,共5页The Chinese Journal of Clinical Pharmacology
基 金:河北省医学科学研究课题基金资助项目(20232116)。
摘 要:目的探讨星形胶质细胞活化在颅脑损伤(TBI)认知障碍中的作用机制。方法将正常SPF级雄性大鼠随机分为对照组、假手术组和模型组,每组10只。对照组不接受外科干预;假手术组仅开骨窗未损伤硬脑膜;模型组在制作骨窗后,用脑损伤仪进行撞击。选取敲除胶质纤维酸性蛋白(GFAP)基因和GFAP过表达的大鼠各10只,处理方式同模型组,设为敲除组和过表达组。用改良神经功能量表(mNSS)评估神经功能,用Morris水迷宫试验评估逃避潜伏期,用实时荧光定量聚合酶链反应法检测星形胶质细胞中GFAP的表达水平,用免疫组化法检测星形胶质细胞的阳性表达情况。结果对照组、假手术组、模型组、敲除组和过表达组的mNSS评分分别为0、0、(9.60±1.17)、(15.20±1.55)和(12.00±1.33)分,第7天的逃避潜伏期分别为(16.15±2.48)、(16.98±2.35)、(40.72±5.42)、(75.42±8.59)和(47.23±6.04)s,星形胶质细胞阳性表达个数分别为(1264.60±135.45)、(1289.20±132.29)、(3269.10±189.39)、(103.90±11.09)和(5301.50±236.29)cell·mm^(-2);对照组、假手术组、模型组和过表达组的GFAP基因表达水平分别为0.86±0.02、0.92±0.04、1.37±0.07和3.42±0.07。过表达组的上述指标与对照组、假手术组、模型组比较,在统计学上差异均有统计学意义(均P<0.05)。结论TBI会造成认知障碍,影响大鼠认知和记忆能力,GFAP基因与星形胶质细胞的活化有关,有助于修复神经损伤。Objective To explore astrocyte activation’s impact on cognitive deficits post-traumatic brain injury(TBI).Methods SPF male rats were divided into control,sham-operation and model groups with 10 rats per group.Control group did not receive the surgical intervention;sham-operation group underwent craniotomy without damaging the dura mater;model group was struck with brain injury instrument after craniotomy.The rats with knockout overexpressed glial fibrillary acidic protein(GFAP)gene were set as the knockout group and overexpression group,with 10 rats per group.The knockout and overexpression groups were treated as the model group.Neurological function was evaluated by modified neurological severity score(mNSS).Escape latency was assessed with the Morris water maze test.The expression levels of GFAP in astrocytes were measured quantitative real-time polymerase chain reaction.The positive expression of astrocytes was determined by immunohistochemistry.Results The mNSS of control,sham-operation,model,knockout and overexpression groups were 0,0,(9.60±1.17),(15.20±1.55)and(12.00±1.33)points;the escape latency period at day 7 was(16.15±2.48),(16.98±2.35),(40.72±5.42),(75.42±8.59)and(47.23±6.04)s;the number of positive astrocytes was(1264.60±135.45),(1289.20±132.29),(3269.10±189.39),(103.90±11.09)and(5301.50±236.29)cell·mm^(-2);the expression levels of GFAP gene in control,sham-operation,model and overexpression groups were 0.86±0.02,0.92±0.04,1.37±0.07 and 3.42±0.07.Compared with overexpression group,the differences of above indexes in control,sham-operation,model,knockout groups were statistically significant(all P<0.05).Conclusion TBI causes cognitive impairment and affects cognition and memory in rats,and the GFAP gene is associated with the activation of astrocytes and helps repair nerve damage.
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