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米诺环素对大鼠蛛网膜下腔出血后早期脑损伤的保护作用
引用本文:陈佳琳,姚声涛,陈良勇,何朝晖,孙晓川,唐文渊,郭宗铎. 米诺环素对大鼠蛛网膜下腔出血后早期脑损伤的保护作用[J]. 第三军医大学学报, 2010, 32(17)
作者姓名:陈佳琳  姚声涛  陈良勇  何朝晖  孙晓川  唐文渊  郭宗铎
作者单位:遵义,贵州省遵义医院儿科,贵州,563002;遵义,贵州省遵义医院神经外科,贵州,563002;重庆医科大学附属第一医院神经外科,重庆,400016
基金项目:贵州省科技厅项目,重庆医科大学优秀博士学位论文资助基金 
摘    要:目的 探讨米诺环素对大鼠蛛网膜下腔出血(subarachnoid hemorrhage, SAH)后早期脑损伤(early brain injury, EBI)的保护作用及其机制.方法 健康4月龄雄性SD大鼠48只,体质量250~300 g,按随机数字表法分为假手术组(sham组)、SAH组、安慰剂组(vehicle 组)和米诺环素组(minocycline组),每组各12只.采用经视交叉前池注血法建立蛛网膜下腔出血模型.各组于处理后24 h经HE染色观察海马CA1区神经元形态;运用Western blot和明胶酶谱方法 检测大鼠海马基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)的表达;采用原位末端标记法(TUNEL)检测海马神经元凋亡.结果 HE染色显示:SAH组大鼠海马CA1正常神经元数量(67.42±20.35)个较sham组(145.5±21.23)个明显下降(P<0.01),米诺环素组正常神经元数量(125.73±24.67)个较SAH组明显增加(P<0.01).Western blot检测结果 显示:sham组大鼠海马MMP-9蛋白表达水平较低(1.94±0.39)%,SAH后24 h MMP-9表达明显增高[(103.60±7 72)%,与sham组相比明显升高,P<0.01];米诺环素组MMP-9蛋白表达明显降低[(74.52±6.47)%,较SAH组明显降低(P<0.01)].明胶酶谱检测显示:sham组大鼠海马未检测到活性[(0.39±0.23)%]、SAH组MMP-9活性(201.81±6 31)%较Sham组明显增高(P<0.01);米诺环素组MMP-9活性(148.96±6.02)%较SAH组明显降低(P<0.01).TUNEL检测显示:sham组海马神经元未检测到TUNEL阳性细胞,SAH后24 h 海马TUNEL阳性细胞数明显增加[(192.17±6 31)个],与sham组相比差异有统计学意义(P<0.01);米诺环素组凋亡阳性细胞数(91.17±7.78)个较SAH组明显下降(P<0.01).结论 大鼠蛛网膜下腔出血后,米诺环素能够改善大鼠海马神经元形态,对早期脑损伤发挥保护作用;其机制可能与米诺环素抑制MMP-9活性及其蛋白表达,减轻海马神经元凋亡有关.

关 键 词:米诺环素  基质金属蛋白酶-9  蛛网膜下腔出血  早期脑损伤

Effect of minocycline on early brain injury after subarachnoid hemorrhage in rats
Chen Jialin,Yao Shengtao,Chen Liangyong,He Zhaohui,Sun Xiaochuan,Tang Wenyuan,Guo Zongduo. Effect of minocycline on early brain injury after subarachnoid hemorrhage in rats[J]. Acta Academiae Medicinae Militaris Tertiae, 2010, 32(17)
Authors:Chen Jialin  Yao Shengtao  Chen Liangyong  He Zhaohui  Sun Xiaochuan  Tang Wenyuan  Guo Zongduo
Affiliation:Chen Jialin1,Yao Shengtao2,Chen Liangyong3,He Zhaohui3,Sun Xiaochuan3,Tang Wenyuan3,Guo Zongduo3 (1 Department of Neurosurgery,2Department of Pediatrics,Zunyi Hospital,Zunyi,Guizhou Province,563002,3Department of Neurosurgery,First Affiliated Hospital,Chongqing Medical University,Chongqing,400016,China)
Abstract:Objective To study the effect of minocycline on early brain injury (EBI) after subarachnoid hemorrhage (SAH) and its mechanism. Methods Forty-eight adult male SD rats were randomly divided into sham operation group,SAH group,vehicle group and minocycline group. A SAH model was induced by injecting autologous arterial blood into the prechiasmatic cistern. Morphology of CA1 region in hippocampus of rats was observed with hematoxylin and eosin (HE) staining in each group. Expression of MMP-9 in hippocampus was...
Keywords:minocycline  matrix metalloproteinase 9  subarachnoid hemorrhage  early brain injury  
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