甘珀酸干预对大鼠脑缺血再灌注损伤的影响  

EFFECT OF CARBENOXOLONE INTERVENTION ON RAT FOCAL CEREBRAL ISCHEMIA-REPERFUSION

作　　者：张桂青[1,2] 麻超[2] 骆翔[1] 喻志源[1] 徐沙贝[1] 王伟[1] 高杰[2] 

机构地区：[1]华中科技大学同济医学院附属同济医院神经内科,武汉430030 [2]新疆石河子大学医学院第一附属医院康复心理科,石河子832008

出　　处：《中国组织化学与细胞化学杂志》2009年第3期261-267,共7页Chinese Journal of Histochemistry and Cytochemistry

基　　金：湖北省自然科学基金项目(2007ABA174);国家杰出青年基金项目(30725019);国家自然科学基金资助项目(30600187)

摘　　要：目的观察缝隙连接阻断剂甘珀酸对局灶性脑缺血/再灌注损伤的影响。方法采用大鼠大脑中动脉阻塞再灌流模型(MCAO),将动物随机分为脑缺血60min再灌注(MCAO)组,脑缺血再灌注加甘珀酸干预(MCAO+CBX)组和假手术组(sham)。采用尼氏染色显示脑梗死灶并计算梗死灶体积;应用免疫荧光与TUNEL染色法分别观察脑缺血后3d与7d不同时间点缺血边缘区胶质纤维酸性蛋白(GFAP)的表达和细胞凋亡情况。结果(1)缺血后3d、7d MCAO+CBX组大鼠梗死体积小于MCAO组,3d、7d MCAO+CBX组大鼠梗死体积较MCAO组分别缩小5%和4.6%;(2)缺血后3d、7d于缺血边缘区可见大量TUNEL阳性染色细胞,且MCAO组大鼠缺血边缘区细胞凋亡数目明显多于MCAO+CBX大鼠(P<0.001);(3)缺血后3d和7d组缺血边缘区GFAP表达明显增强,3d的MCAO组与MCAO+CBX组大鼠缺血边缘区GFAP的表达均较假手术组强(P<0.05),7d的MCAO+CBX组大鼠缺血边缘区GFAP的表达较假手术组强(P<0.001),但明显弱于MCAO组大鼠(P<0.01);结论缝隙连接阻断剂甘珀酸可减少大鼠大脑中动脉阻塞后脑梗死体积,其机制可能与阻断缝隙连接后缺血边缘区神经元凋亡降低有关,星型胶质细胞的反应性变化参与了该过程。Objective To observe the effect of obstructing the gap junction on focal cerebral ischemia. Methods Rat middle cerebral artery occlusion reperfusion models （MCAO） were applied, and the animals were randomly divided into the 60min ischemia-reperfusion （MCAO） group, ischemia-reperfusion plus car- benoxolone intervention （MCAO ＋ CBX） group and sham operation group （Sham） . Cerebral infarction focus was showed and the volume was calculated by Nissl staining. At different time points of 3d and 7d after ischemia, marginal GFAP expression and apoptosis were observed by immunofluorescence and TUNEL. Results （1） 3d and 7d after ischemia the infarct volume was significantly less in the MCAO ＋ CBX group than in the MCAO group （5% and 4. 6%, respectively）; （2） 3d and 7d after ischemia, apoptotic cells in the marginal area of MCAO rats was significantly more than that in MCAO ＋ CBX rats （P〈0. 001） ; （3） 3d and 7d after ischemia , GFAP expression increased on the edge of ischemic area; on d3 MCAO and MCAO ＋ CBX groups showed more GFAP expression than the sham group （P〈0. 05）, on d7 MCAO ＋ CBX group show much stronger GFAP expression than that in the sham group （P〈0. 001） , but obviously weaker than that in MCAO rats （P〈0.01） . Conclusion Obstructing the gap junction can reducing cerebral infarct volume after focal cerebral ischemia, which may be related to reduce neuronal apoptosis of the marginal ischemic area by obstructing the gap junction, and glial cell reactive changes might play an important role in this process.

关 键 词：甘珀酸 大鼠脑缺血 神经元 凋亡 

分 类 号：R322.811[医药卫生—人体解剖和组织胚胎学]