胍丁胺对脑缺血再灌注大鼠血脑屏障通透性水通道蛋白4和基质金属蛋白酶9的影响  

Effects of agmatine on permeability of blood-brain barrier and expression of aquaporin 4 and matrix metalloproteinase 9

作　　者：徐鑫淼[1] 金勇君[2] 郭伟[3] 曹鹏娟 曲甜甜[2] 杨美子[4] 

机构地区：[1]滨州医学院,烟台264003 [2]滨州医学院烟台附属医院,烟台264003 [3]滨州医学院附属医院,烟台264003 [4]滨州医学院药学院,烟台264003

出　　处：《中华行为医学与脑科学杂志》2015年第3期204-207,共4页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：山东省自然科学基金项目（ZR2012HM057）;山东省教育厅科技计划项目（J07YD21）

摘　　要：目的 研究胍丁胺对脑缺血再灌注损伤后血脑屏障（blood brain barrier,BBB）通透性的保护和水通道蛋白4（AQP4）、基质金属蛋白酶9（MMP9）表达的影响.方法 采用随机数字表法将60只大鼠随机分为正常对照组、模型组、治疗组,每组n=20.采用栓线法制备大鼠大脑中动脉阻断（middle cerebral artery occulation,MCAO）模型.正常组切开缝合皮肤后2h腹腔注射生理盐水;模型组建立大鼠MCAO模型后2h进行再灌注,同时腹腔注射生理盐水;治疗组建立MCAO模型后2h腹腔注射胍丁胺.通过测定血脑屏障的通透性考察血脑屏障的损害程度,利用TTC染色比较梗死灶大小,电镜观察神经元形态学变化,采用免疫组织化学法检测脑组织AQP4、MMP9的表达.结果 血脑屏障的通透性胍丁胺治疗组（0.31±0.10）较模型组（0.46±0.09）显著性下降（P＜0.05）,但是明显高于正常对照组（0.24±0.12） （P＜ 0.05）.正常对照组无梗死灶,胍丁胺组较模型组梗死灶明显减小.与模型组比较,胍丁胺治疗组变性神经元数明显减少,神经元的病变程度也得到明显改善.模型组、胍丁胺组左侧大脑半球顶叶皮层缺血半暗带AQP4和MMP9的表达量与正常对照组相比均显著增多,差异有统计学意（P＜0.05）.模型组左侧大脑半球顶叶皮层缺血半暗带AQP4和MMP9的表达明显高于胍丁胺组相应部位脑组织AQP4和MMP9的表达,差异有统计学意义（P＜0.05）.结论 胍丁胺可下调脑组织AQP4和MMP9的表达,从而对血脑屏障的损伤起保护作用.Objective To investigate the protection of agmatine on blood brain barrier （BBB） permeability and the effect on the expression of aquaporin 4 （AQP4） and matrix metalloproteinase 9 （MMP9） in ischemic reperfusion injury rats.Methods Sixty healthy male Sprague-Dawley rats were randomly divided into normal control group （NC）,model group and agmatine group,and there were 20 rats in each group.Normal control group was treated with intraperitoneal injection of saline in 2 hours after incision and suture of skin.Model group was treated with intraperitoneal injection of saline in 2 hours after the establishment of middle cerebral artery occulation （MCAO） model.Agmatine group was treated with intraperitoneal injection of agmatine （AGM） in 2 hours after the establishment of MCAO model.The damage of blood brain barrier was detected by measuring the permeability of blood brain barrier.The infarct size of brain was observed with TTC staining.The morphological changes of neurons were observed with electron microscope.The expressions of AQP4 and MMP9 were detected using immunohistochemical method.Results The permeability of BBB of agmatine treatment group （0.31±0.10） decreased significantly compared with the model group （0.46±0.09） （P〈0.05）,but was still significantly higher than the normal control group （0.24±0.12） （P〈0.05）.There was no infarction area in normal control group and the infarction areas of agmatine group decreased obviously compared with the model group.Compared with model group,the number of neurons with morphological changes reduced significantly and the degree of pathological changes of neurons was obviously improved in agmatine group.Compared with normal control group,the expression of AQP4 and MMP9 in ischemic penumbra of left cerebral hemisphere parietal cortex in the rats of model group and agmatine group increased significantly（P〈0.05）.And the expression of AQP4 and MMP9 in model group was significantly higher than that of agmatine group（P〈0.05�

关 键 词：水通道蛋白4 基质金属蛋白酶9 胍丁胺 脑缺血再灌注 

分 类 号：R285.5[医药卫生—中药学]