大鼠脑缺血半暗带区外周型苯二氮卓受体的变化及黄芪甲苷的影响  

Changes of PBRs in penumbra area after cerebral ischemia-reperfusion injury and effects of astragaloside Ⅳ in rats

作　　者：李聪聪[1] 陈春富[1] 王爱武[2] 冯亚波[1] 程红霞[3] 张汶汶[4] 辛玮[4] 

机构地区：[1]山东大学附属省立医院神经内科,山东济南250021 [2]山东大学附属省立医院药剂科,山东济南250021 [3]山东大学附属省立医院病理科,山东济南250021 [4]山东大学附属省立医院中心实验室,山东济南250021

出　　处：《中国药理学通报》2013年第6期846-850,共5页Chinese Pharmacological Bulletin

基　　金：山东省自然科学基金重点项目(No Z2007C03)

摘　　要：目的观察大鼠脑缺血/再灌注损伤后半暗带区外周型苯二氮卓受体(peripheral-type benzodiazepine receptors,PBRs)的变化,研究不同剂量黄芪甲苷(astragalosideⅣ,AST)对PBRs的影响。方法将60只大鼠随机分为假手术组、模型组、AST 10、40和100 mg.kg-1组5组。采用线栓法制作大鼠大脑中动脉缺血模型,于缺血2 h后再灌注24 h。采用Bederson方法进行神经功能评分,采用梯度离心法提取缺血半暗带区线粒体,应用放射配基结合实验检测线粒体[3H]PK11195特异性结合活性,测定PBRs最大结合容量(Bmax)和平衡解离常数(Kd)。结果线粒体PK11195特异性结合活性与动物神经功能缺损评分具有明显相关性(r=0.833,P<0.01)。与模型组相比,AST 10(P<0.05)、40(P<0.01)、100(P<0.01)mg.kg-1组动物神经功能障碍评分均明显减少,AST 40 mg.kg-1组与AST 100 mg.kg-1组相比,差异无显著性(P>0.05)。与模型组相比,AST 10(P<0.05)、40(P<0.01)、100(P<0.01)mg.kg-1组半暗带区Bmax明显减少。与AST 10 mg.kg-1组相比,AST 40(P<0.05)、100(P<0.01)mg.kg-1组Bmax明显减少(P<0.01)。AST 40 mg.kg-1组和100 mg.kg-1组相比,Bmax及动物神经功能缺损评分差异均无显著性(P>0.05)。各组Kd值差异无显著性(P>0.05)。结论 AST可通过降低脑缺血/再灌注后PBRs表达起到脑保护作用。Aim To investigate the changes of periph- eral-type benzodiazepine receptors （PBRs） in penum- bra after cerebral ischemia-reperfusion injury and the effects of astragaloside Ⅳ on PBRs in rats. Methods Sixty SD rats were randomly divided into sham-opera- tion group, model group and astragaloside Ⅳ （AST, 10 mg . kg-1, 40 mg .kg-1 or 100 mg. kg-1） treat- ment groups. The unilateral middle cerebral artery models were induced by clue-blocked method. Neuro- logical deficit scores were examined with Bederson＇ s method. For binding analysis, the animals were sacri-riced after 2-hour ischemia and 24-hour reperfusion and the mitochondria from penumbra area were purified by discontinuous gradient centrifugation. Using radioli- gand assays with the selective antagonist [^3H ] PK 11195, PBRs density （B ） and affinity were measured. Results A positive relationship was found between [^3H] PK11195 binding activity in mitochon- dria and neurological deficit scores in rats （r = 0. 833, P 〈 0. 01 ）. Compared to model group, neurological defieit scores decreased in AST 10 （P 〈0. 05） , 40 （P 〈 0. 01 ） , and100（ P 〈 0.01 ）mg . kg-1groupsre-spectively; no significant difference was found between 40 mg. kg-1 and 100 mg .kg-1 groups （P 〉0.05）. Compared to model group, B_max in penumbra area de- creased in AST 10 （P 〈0.05）, 40 （P 〈0.01）, and 100 （P 〈0.01） mg . kg-1 groups respectively. Compared to AST 10 mg . kg-1 group, B_max in penumbra area decreased in AST 40 and 100 （P 〈 0.05） mg. kg-1 groups respectively. No significant difference was found between 40 mg . kg-1and 100 mg. kg-1 groups （P 〉 0.05 ） in B_max and neurological deficit scores re-spectively. On the contrary, the Scatchard analysis re- vealed that AST-treated rats showed no significant changes in Kd when compared with those in sham-oper- ation group and model group, respectively. Conclu- sion Astragaloside Ⅳ can protect ischemia brain tis- sue by inhibiting the expression of PBRs after cerebral

关 键 词：脑缺血 再灌注 半暗带 线粒体 外周型苯二氮卓受体 黄芪甲苷 大鼠 

分 类 号：R-332[医药卫生] R284.1